Burden of Poverty


Lacking money or time can lead one to make poorer decisions, possibly because poverty imposes a cognitive load that saps attention and reduces effort.
Mani et al. (p. 976; see the Perspective by Vohs) gathered evidence from shoppers in a New Jersery mall and from farmers in Tamil Nadu, India. They found that considering a projected financial decision, such as how to pay for a car repair, affects people’s performance on unrelated spatial and reasoning tasks. Lower-income individuals performed poorly if the repairs were expensive but did fine if the cost was low, whereas higher-income individuals performed well in both conditions, as if the projected financial burden imposed no cognitive pressure. Similarly, the sugarcane farmers from Tamil Nadu performed these tasks better after harvest than before.

http://m.sciencemag.org/content/341/6149/976.abstract

Amgen buys Onyx Pharmaceuticals for $10.4B


The acquisition represents the fifth-largest biotechnology deal in history

Amgen Inc struck a deal to buy cancer drug maker Onyx Pharmaceuticals Inc for about $10.4 billion on Sunday, as it moves to restock its product pipeline in response to declining sales of its flagship anemia drugs.

Tony Coles, M.D., ONyx Pharmaceuticals Inc. CEO

Tony Coles, M.D., ONyx Pharmaceuticals Inc. CEO

The acquisition represents the fifth-largest biotechnology deal in history. It gives Amgen full rights to Kyprolis, the new multiple myeloma drug that analysts expect to reach annual peak sales in excess of $2 billion.

The world’s largest biotechnology company will also gain a revenue stream from the liver and kidney cancer drug Nexavar that Onyx shares with Bayer AG, as well as royalty payments on Bayer’s much newer colon cancer drug, Stivarga, and potential future royalties on an experimental breast cancer drug being developed by Pfizer Inc.

Amgen to pay $125 per share for Onyx

Amgen expects deal to add to adjusted earnings in 2015

Deal gives Amgen pipeline of cancer drugs

Fifth-biggest biotech deal in history

 

Thousand Oaks, California-based Amgen has faced growing pressure to beef up its drug development pipeline as safety concerns have trimmed sales of its flagship anemia drugs, Aranesp and Epogen. Also, patents on four of its five top-selling drugs are set to expire starting in 2015.

Robert A. Bradway, Amgen Inc. CEO

Robert A. Bradway, Amgen Inc. CEOting in

Cancer medicines are the holy grail for many drugmakers because current products have limited effectiveness and the companies can charge steep prices for new biotech treatments.

Amgen said it will pay $125 per share for Onyx, a 4.2 percent increase from the $120 a share it offered in June. Onyx said that bid significantly undervalued the company and put itself up for sale.

The companies expect the deal to close in the beginning of the fourth quarter. Amgen expects it to add to adjusted net income in 2015.

Discussions between Amgen and Onyx hit a snag earlier this month after Amgen sought access to data from Onyx’s ongoing clinical trials, people familiar with the matter told Reuters previously. A source familiar with the matter on Sunday said that Amgen believed it had done extensive due diligence and was comfortable with the purchase.

Onyx shares closed at $116.96 on Friday. They closed at $85.50 on June 28, before reports of Amgen’s $120-a-share bid surfaced.

Amgen’s biggest deal since 2001

The Onyx deal is Amgen’s biggest since its $16 billion acquisition of Immunex in 2001 which gave it the rheumatoid arthritis drug Enbrel, now one of Amgen’s biggest-selling products.

It is also by far the biggest deal under CEO Bob Bradway, who assumed the top spot in May 2012. He has done a handful of much smaller deals, the biggest to date being a $1.16 billion acquisition of Micromet.

Large pharmaceutical companies have increasingly been looking to acquire smaller biotech firms to gain access to new drugs, as they face significant revenue losses stemming from expired patents.

This helped drive up the volume of healthcare M&A in the first six months of 2013 more than 30 percent compared with the same period last year.

Recent deals include generic drugmaker Actavis Inc’s $8.5 billion acquisition of Warner Chilcott and Human Genome Sciences’ $3 billion sale to GlaxoSmithKline Plc.

The Onyx deal is expected to give Amgen a much higher profile in oncology. Several of its current drugs offer supportive care for cancer patients, such as treating anemia or decreases in white blood cells caused by chemotherapy.

Another of Amgen’s newer medicines, Xgeva, helps prevent fractures in patients whose cancer has spread to the bone. Its one product that treats cancer, the colon cancer drug Vectibix, has been largely a disappointment.

Analysts expected Onyx revenue to reach $878 million in 2014, according to Thomson Reuters I/B/E/S.

 

Perrigo Company to Acquire Elan Corporation, plc for US$8.6 Billion, Becoming Premier Global Healthcare Company


 Perrigo strengthens business and financial profile with highly diversified revenue streams and enhanced cash flows

Perrigo Chairman and CEO, Joseph C. Papa

Perrigo Chairman and CEO, Joseph C. Papa

Perrigo Company and Elan Corporation, plc, a leading biotechnology company headquartered in Ireland, today announced that, following a formal sale process conducted by Elan, Perrigo and Elan have entered into a definitive agreement under which Elan will be acquired by a new holding company incorporated in Ireland (“New Perrigo”).

The cash and stock transaction, which is valued at approximately US$8.6 billion based on the closing price of Perrigo shares on 26 July 2013 (US$6.7 billion excluding Elan’s cash on hand), will create a global healthcare company with an industry-leading growth profile and the geographic scale and scope to continue building a truly differentiated business.

“Through this transaction, Perrigo establishes a diversified platform for further international expansion,” stated Perrigo Chairman and CEO, Joseph C. Papa. “We believe this transaction is compelling for Elan shareholders and fully takes into account the value of Elan’s assets, including a large cash balance and a double-digit royalty claim on Tysabri(R), a blockbuster product that generated revenues of US$1.6 billion last year and has been growing at a compound annual growth rate of 19%. We believe the combination of Perrigo and Elan will create an industry-leading global healthcare company with the balance sheet liquidity and operational structure to accelerate our growth and capitalize on international market opportunities.”

Mr. Robert A. Ingram, Chairman of Elan, commented, “This is an excellent transaction for Elan shareholders and provides them with cash consideration as well as the opportunity to benefit from the potential upside value of the new company. Joe Papa and his team have demonstrated exceptional capability and delivery of results in building a premier healthcare company over the past number of years. We have the confidence in Joe and his leadership team to continue to grow and expand its presence on a global scale.”

Additionally, Elan CEO Mr.

G. Kelly Martin, Elan CEO

G. Kelly Martin, Elan CEO

said, “The Elan platform has been constructed over the years to provide a unique and compelling investment thesis for our shareholders. This transaction underscores the tremendous value of Elan’s platform. The new combined company should deliver value, growth and diversification to shareholders for many years to come.”

The proposed transaction, which has been unanimously approved by the respective boards of directors of Perrigo and Elan, is expected to close by the end of calendar year 2013. At the close of the transaction, Perrigo and Elan will be combined under New Perrigo, a new company incorporated in Ireland, where Elan is incorporated today. New Perrigo, which is expected to be called Perrigo Company plc or a variant thereof, will be led by Perrigo’s current leadership team.

Elan’s current business portfolio includes royalties from Multiple Sclerosis (MS) treatment Tysabri(R) (marketed and distributed by Biogen Idec, Inc.), along with a neuropsychiatric pipeline with near term value-creating opportunities. Tysabri(R) had a 19% compound annual growth rate over the 2008-2012 period. Elan currently earns a 12% royalty on global net sales of Tysabri(R).From 1 May 2014 onwards, the royalty increases to 18% on annual net sales up to US$2.0 billion, and to 25% on annual net sales above this amount. The Tysabri(R) cash flows are highly sustainable with multiple barriers to entry, analogous to the fundamentals of Perrigo’s core business. Further upside exists if Tysabri(R) is approved for Secondary Progressive MS.

Key benefits of the transaction for Perrigo and Elan:

  •  Platform for International Expansion — Operating base in Ireland to serve as a business hub and gateway for expansion into international markets
  • Scale, resources and corporate structure to drive strategic initiatives and investments
  • Differentiated business model well-positioned to continue growth in core markets and to expand to other international markets
  • Strong Business and Financial Profile — Highly diversified revenue stream
  • Strong pro forma cash flows to continue to support an investment grade credit profile
  • Robust and sustainable growth outlook
  •  Financially Compelling — Enhances revenue, adjusted EBITDA and earnings growth rates and expands margins
  • Immediately accretive to Perrigo adjusted earnings per share in 2014
  • Meaningful synergy opportunities

Benefits to Elan Shareholders

  • Upfront value unlocked via the cash consideration, while Elan Shareholders will also have the opportunity to participate in the benefits of New Perrigo
  • Perrigo management team with strong track record of successfully acquiring and integrating diverse businesses

The combination is expected to result in more than US$150 million of recurring after-tax annual operating expense and tax savings. Certain of these synergies result from the elimination of redundant public company costs while optimizing back-office support and the global R&D functions. Additionally, tax savings are expected to arise from the combined company being incorporated in Ireland with organizational, operations and capitalization structures that will enable the combined company to more efficiently manage its global cash and treasury operations.

Mr. Papa concluded, “We are very impressed with the accomplishments of Elan’s leadership team. Over the past decades, they have built a company that delivers high quality healthcare products with a focus on innovations in science to fill significant unmet medical needs around the world. This strategic transaction aligns with Perrigo’s acquisition strategy and our previously-stated intentions to grow our international business. We expect New Perrigo to create tremendous value for our shareholders for years to come.”

Perrigo has secured an aggregate amount of US$4.35 billion in fully underwritten bridge financing commitments from Barclays and HSBC Bank USA, N.A., which, in addition to Perrigo cash on hand, are available to finance the cash portion of the transaction, pay fees and expenses related to the transaction and refinance Perrigo’s existing indebtedness including its current term loan, private placement notes and existing public bonds. Perrigo plans to refinance and repay the bridge borrowings through new debt issuances and the use of Elan cash on hand.

 

Roche and AstraZeneca join forces on R&D initiative


AstraZenecaRoche and AstraZeneca announced today a new collaboration to share a specific type of early research data related to drug design, which could further accelerate the discovery of high quality compounds with an increased chance of clinical success. Using a dedicated technology (Matched Molecular Pair Analysis, MMPA) modifications will be identified, which companies can apply to their compound structures in order to improve their metabolism, pharmacokinetics or safety, without divulging confidential information about their chMedchemicaemical structures. This gives both companies the opportunity to efficiently reapply useful medicinal chemistry know-how embedded in their combined databases of experimental results, in order to identify potential new drug candidates using fewer rounds of design, synthesis and testing. Both Roche and AstraZeneca will make their selected databases available for this type of joint analysis and are committed to making the data generated available to the broader research community, including research foundations, charities and academia.

Commenting on this collaboration, Luca Santarelli, Head of Neuroscience and Small Molecule Research at Roche, sRocheaid: “It is unique in the history of our industry that two major players are sharing their know-how at such an early stage of research. We believe that this transparency of small molecule optimization knowledge, in a smart and thoughtful way, could profoundly enhance our ability to design drugs, be of benefit for all parties involved and ultimately help bring better medicines to patients.”

“AstraZeneca has taken multiple steps to both open our compound libraries to those wishing to find exciting new chemistries for early drug discovery and to share compound related datasets that will allow our industry to speed the discovery of new medicines,” said Mike Snowden, head of Discovery Sciences in Innovative Medicines and Early Development (IMED), which initiated the collaboration. “Researching a potential new medicine is a long race that we strive to complete with urgency to fill unmet medical need. We are making these data sets available in the belief that – when paired with findings from other companies through a common platform – we can reach our patients faster with medicines that make a meaningful difference to their lives.”

The data-sharing will be managed through the intermediary company, MedChemica, which has expertise in the key technology of MMPA. The consortium is open to other large companies to add their knowledge thereby gaining access to and enhancing this resource.  More data added to this system will raise the quality and specificity of drug design rules.

Alexander Dossetter, Managing Director at MedChemica said, ‘We congratulate both companies for taking the courageous first step of sharing medicinal chemistry knowledge. We aim to expand this kind of collaboration and eventually go beyond facilitating chemical building blocks into chemical lead hunting and optimization.  The goal is that resources will be better utilized and patients better served.”

Cellgene and Morphosys: $818M deal to advance CD38 cancer program MOR202 for Multiple Myeloma


Development of novel therapeutic antibody approach being evaluated in clinical trials for patients with multiple myeloma

  • Celgene secures worldwide rights to MOR202, whereby the companies will jointly develop MOR202 globally and co-promote the product in Europe
  • MosphosysMorphoSys retains a 50/50 profit sharing in its co-promotion territory and is eligible to receive tiered double-digit royalties outside of the co-promotion territory

MorphoSys AG (FSE: MOR; Prime Standard Segment, TecDAX) and Celgene Corporation (NASDAQ: CELG) announced an agreement to jointly develop MOR202 globally and to co-promote MOR202 in Europe. MOR202 is a fully human monoclonal antibody targeting CD38 to treat patients with multiple myeloma (MM)Celgene and certain leukemias. MOR202 is currently being evaluated in a phase 1/2a trial in patients with relapsed/refractory myeloma. MorphoSys and Celgene will collaborate on the development of MOR202 in multiple myeloma and other indications and share costs on a 1/3:2/3 basis.

Under the terms of the agreement, MorphoSys will receive an upfront license fee of EUR 70.8 million (US $92 million) and Celgene will invest EUR 46.2 million (US $60 million) to subscribe for new shares of MorphoSys AG. The new shares will be issued at a price to be determined upon the transaction becoming effective following clearance by the US antitrust authorities under the Hart-Scott-Rodino Act. The share price will include at least a premium of 15% of the closing price of the MorphoSys share prior to the signature of the agreement. MorphoSys may be entitled to receive additional development, regulatory and sales milestones, in addition to tiered double digit royalties on net sales outside the co-promotion territory. MorphoSys retains a 50/50 profit sharing in its co-promotion territory. The total potential value of this transaction, assuming all development, regulatory and sales milestones are reached, may be up to EUR 628 million (US $818 million).

“This alliance takes MorphoSys to the next stage of our corporate development. By moving up the value chain we have the opportunity to develop a commercial organization that expands on our significant research, development and technology expertise of today. Targeting CD38 has matured to be a highly innovative and very promising approach in multiple myeloma and we are committed to retain a larger share of the potential upside. Celgene, one of the leading innovators in multiple myeloma, is the ideal partner to develop the compound efficiently and deliver to patients with multiple myeloma worldwide,” commented Dr. Simon Moroney, Chief Executive Officer of MorphoSys AG.

“Strategic investments in next generation medical innovation make it possible for physicians to turn incurable cancers like multiple myeloma into chronic, more manageable diseases,” said Mark Alles, Executive Vice President and Global Head of Hematology and Oncology at Celgene Corporation. “This collaboration with MorphoSys enables us to rapidly advance a promising therapeutic antibody in a disease where significant progress is being made, but where patients continue to need new treatment options.”

“Today’s news marks our second major alliance on a proprietary compound that we have brought from target identification to clinical development. MOR202 has become a very attractive asset in our proprietary portfolio and the target CD38 is a validated highly promising target for patients with multiple myeloma. We are looking forward to expanding and accelerating the clinical development of MOR202 in collaboration with one of the leading developers of cancer therapeutics in the field,” commented Dr. Arndt Schottelius, Chief Development Officer of MorphoSys AG.

MOR202 is a HuCAL antibody targeting CD38 to treat patients with multiple myeloma (MM) and certain leukemias and is currently being evaluated in a phase 1/2a trial in patients with relapsed/refractory myeloma. CD38 is a protein found on the surface of these tumor cells that acts as a target for the MOR202 antibody. Once attached, the MOR202 attracts natural killer cells in the body to identify and kill the tumor cells. In multiple preclinical studies, MOR202 has shown encouraging results as mono therapy and synergistic effects with both a proteasome inhibitor and lenalidomide, an oral immunomodulatory therapy.

The agreement between MorphoSys and Celgene is subject to clearance by the US antitrust authorities under the Hart-Scott-Rodino Act, and will become effective as soon as this condition has been met.

GlaxoSmithKline is backing another venture fund specialized in rare diseases


GlaxoSmithKline is backing another venture fund. The London-based drug giant has committed €17.5 million ($23.09 million) for a VC vehicle focused on rare diseases startups in Europe, building on its previous investments in venture firms on both sides of the Atlantic.Gold Coins and plant isolated on white background

Like other pharma groups, GSK has made a point to allocate R&D dollars to the research of rare diseases, which affect no more than one and 2,000 people. The company ($GSK) is now leading development of a therapy against the rare genetic disease Duchenne muscular dystrophy in collaboration with Prosensa, seeking to deliver what could be the first drug for the muscle-wasting disorder.

Also, the pharma giant set up a research unit in 2010 that focuses on development of treatments for orphan diseases, which typically command top dollar and present hurdles to generics competition. With the new venture fund focused in the field, Glaxo is investing alongside CDC Entreprises, Idinvest Partners and VC heavyweight New Enterprise Associates (NEA), Reuters reported. France’s Kurma Life Sciences Partners is leading the new fund, dubbed Kurma Biofund II, which has attracted €44 million ($58.19 million) so far.

Kurma aims to work with a network of research institutes in Europe to pinpoint worthy science in the rare-diseases field and capitalize new biotech outfits. Glaxo has a track record of seeding startups in partnership with venture players. In April the company announced a new VC vehicle with Avalon Ventures in San Diego to provide up to $495 million for 10 startups focused on new disease targets. And that deal followed GSK’s $50 million investment in Sanderling Ventures’ latest fund. Last year the company joined forces with Johnson & Johnson ($JNJ) to back a $200 million life sciences fund from Index Ventures, which has begun to use the money to seed and invest in asset-focused biotech startups. Almost all major pharma companies have acknowledged that they need to step up to fund innovative startups as other financial powerhouses have stepped back because of the high risk and past failures of such ventures.

Lundbeck, Otsuka Expand Alzheimer's Alliance


Lundbeck and Otsuka Further Expand Their Alliance and Enter Into Collaboration for the Development and Commercialization of Lu AE58054 in Development for Alzheimer’s Disease

  • Clinical phase II data will be presented at the AAIC in Boston in July 2013
  • A phase-III program of more than 2,500 patients will commence during 2013
  • Lundbeck receives from Otsuka USD 150 million upon signing of the deal
  • Within the two companies’ global agreement this is the first of the projects that will ultimately involve co-development and co-promotion of three Lundbeck drug candidates

H. Lundbeck A/S and Otsuka Pharmaceutical Co., Ltd.   announced a license and development agreement for Lu AE58054, a selective 5HT6 receptor antagonist currently in development for the treatment of Alzheimer’s disease. Under the terms of the agreement, Lundbeck will grant Otsuka co-development and co-commercialization rights to Lu AE58054 in the U.S., Canada, East Asia including Japan, major European countries and Nordic countries.

Under the terms of the agreement, Lundbeck will receive from Otsuka an initial payment of USD 150 million (approximately DKK 855 million) upon signing. Both companies will share the sales, development, and commercialization costs based on the agreement. Lundbeck is also entitled to up to USD 675 million (approximately DKK 3.9 billion) in regulatory and sales milestones. Additional specific financial terms of the agreement remain undisclosed.

Taro Iwamoto, President and Representative Director of Otsuka Pharmaceutical Co., Ltd., noted with respect to Lu AE58054 “The global collaboration between Otsuka and Lundbeck continues to grow stronger with the addition of Lu AE58054.  Not only does the product further enhance the synergy between the companies as we work together to bring to the market solutions for better health, Lu AE58054 is a potentially promising development in a very difficult disease area.”

 

The pivotal clinical program with Lu AE58054 is planned to be initiated later in 2013. The global program will consist of several studies and include more than 2,500 patients. The first phase III study will enroll patients with mild-to-moderate Alzheimer’s disease. Lu AE58054 will be tested as adjunct treatment to donepezil. Subsequent studies are expected to be initiated towards the end of 2013.

Ulf Wiinberg, President & Chief Executive Officer of Lundbeck commented “There is a serious, global, unmet medical need regarding treatments for Alzheimer’s disease in aging populations. Together, Otsuka and Lundbeck with their development capabilities, commercial experience and geographical reach will provide a solid foundation in the development of Lu AE58054.”

In May 2012, it was announced that Lu AE58054 had met its primary endpoint in a fixed dose, randomized, placebo-controlled, 24-week clinical study in 278 patients. The study was conducted in patients suffering from moderate Alzheimer’s disease, with Lu AE58054 administered as an add-on to donepezil, a commonly used acetylcholinesterase inhibitor[i]. The clinical data from the phase II study is planned to be presented at the annual Alzheimer’s Association International Conference (AAIC) in Boston on 13-18 July 2013.

About Lu AE58054I

Lu AE58054 is a selective 5-HT6-receptor antagonist. The 5-HT6-receptor is primarily found in areas of the brain involved in cognition. A number of early trials have demonstrated that a 5-HT6-receptor antagonist could offer potential benefits in the treatment of disorders such as Alzheimer’s disease and in November 2009 Lundbeck initiated the above described 24 week clinical phase II trial with Lu AE58054 as augmentation therapy in Alzheimer’s disease.

About Alzheimer’s disease

Alzheimer’s disease is a progressive brain disorder, in which the brain gradually degenerates. It most frequently occurs in people aged above 65—70 years. People with Alzheimer’s disease develop distressing changes in memory, thought, function and behavior, which worsen over time. These changes increasingly impact upon the person’s daily life, reducing their independence, until ultimately they are entirely dependent on others.

Alzheimer’s disease also has an enormous impact on the patient’s caregiver. Most caregivers are close relatives who provide care in the home — a demanding and exhausting role that represents an emotional and physical burden[ii].

Alzheimer’s disease is associated with damages and death of brain cells, leading to significant brain shrinkage and neurotransmitter imbalances. As the brain cells degenerate, characteristic waste accumulates in the brain, known as ‘plaques’ and ‘tangles’.

Worldwide, 36 million people have dementia. Perhaps as many as 28 million of the world’s 36 million people with dementia have yet to receive a diagnosis and, therefore, do not have access to treatment, information and care. Every year, an estimated 4.6 million new cases are identified[iii]. With the shift towards an increasingly elderly population, it is predicted that the number of people affected by dementia will almost double every 20 years, and by the year 2050, 115 million people will have the condition[iv].

Alzheimer’s disease is the most common cause of dementia, accounting for 50—70% of cases[v].

The worldwide costs of dementia (USD 604 billion in 2010) amount to more than 1% of gross domestic product (GDP).

 

Edison and Dainippon Sumitomo sign a $545M Development Deal


 

Edison Pharmaceuticals, Inc. signs licensing agreement with Dainippon Sumitomo Pharma Co., Ltd. for development & commercialization of orphan mitochondrial and adult central nervous system disease drugsedison_logo
Edison Pharmaceuticals announced that it has entered into a research/development and commercialization agreement with Dainippon Sumitomo Pharma Co., Ltd. (DSP) for the development of EPI-743 and EPI-589 in Japan. Under the terms of the agreement, DSP will gain development and commercialization rights in Japan in exchange for Edison receiving $35 million in upfront and $15 million in R&D support. In addition, Edison will be eligible to receive $10-35 million in development milestones per indication and up to $460M in commercial milestone payments as well as royalties on commercial sales.
The initial scope of the transaction includes both pediatric orphan inherited mitochondrial and adult central nervous system diseases. Under the terms of the agreement, DSP will undertake activities required for development, approval, and commercialization of EPI-743 in Japan. The work will initially focus on orphan pediatric mitochondrial disease. Edison will retain 100% ownership and direct all research, clinical, and commercial development of EPI-743 and EPI-589 outside of Japan.
In addition, the parties will collaborate on the research and development of EPI-589 with a focus on adult central nervous system disease. This collaboration is based upon the emerging body of data implicating redox and mitochondrial dysfunction as a root cause of neurologic disorders.
Edison’s translational platform is based on redox biochemistry.  It bridges key learnings derived from genetically confirmed pediatric rare mitochondrial disease to adult central nervous system disorders where redox and mitochondrial dysfunction are likely to also play a critical role.
The Edison redox platform consists of proprietary laboratory and clinical tools that enable the discovery, optimization, and clinical validation of redox-directed drugs. Specifically, through employing both laboratory and clinically derived redox signatures of disease and drug action, Edison is able to develop drugs at a fraction of the time and cost of current drug development processes, thereby reducing risk and cost and increasing the likelihood of success.
Edison will use proceeds derived from the partnership to advance the late stage development and commercialization of EPI-743 for Leigh syndrome and Friedreich’s ataxia, as well as to advance EPI-743 in other exploratory phase 2 trials for rare pediatric diseases with shared mitochondrial mechanisms.
“Our partnership with Dainippon Sumitomo Pharma will allow Edison to accelerate the development and approval of the first drug for inherited respiratory chain diseases of the mitochondria,” stated Guy Miller, MD, PhD, Chairman and CEO of Edison. “Our shared vision of the role of redox control and the mitochondria in human disease will help us extend our learnings derived from rare pediatric diseases to poorly treated acute and chronic adult CNS diseases.”
EPI-743 & EPI-589
EPI-743 is an orally bioavailable small molecule being developed by Edison Pharmaceuticals for the treatment of inherited mitochondrial diseases. EPI-743 is a member of the para-benzoquinone class of drugs. It serves as a cofactor for the novel drug target– NADPH quinone oxidase 1 (NQO1). Through a redox-based mechanism, EPI-743 augments endogenous glutathione biosynthesis– essential for the control of oxidative stress. EPI-589 is a next-generation, reversible redox cofactor being developed for a variety of adult diseases.
The positive clinical results of a phase 2A trial of EPI-743 in children with Leigh syndrome were recently reported in Molecular Genetics and Metabolism (EPI-743 reverses the progression of the pediatric mitochondrial disease—Genetically defined Leigh Syndrome 107 (2012) 383-388). Separate manuscripts detailing EPI-743 treatment effect on CNS and systemic glutathione biomarker levels are also reported in Molecular Genetics and Metabolism (Brain uptake of Tc99m-HMPAO correlates with clinical response to the novel redox modulating agent EPI-743 in patients with mitochondrial disease 107 (2012) 690-699; Glutathione: A redox signature in monitoring EPI-743 therapy in children with mitochondrial encephalomyopathies (2013), in press).
Edison Pharmaceuticals
Edison Pharmaceuticals is a specialty pharmaceutical company dedicated to developing treatments for children and adults with orphan mitochondrial diseases. EPI-743 is in phase 2 clinical development for the treatment of inherited respiratory chain disorders. Double-blind placebo-controlled trials are ongoing for the following indications: Leigh syndrome, Friedreich’s ataxia, Cobalamin C defect, and Undiagnosed Disorders of Oxidation-Reduction.
Dainippon Sumitomo Pharma Co., Ltd.
Dainippon Sumitomo Pharma Co., Ltd. (DSP) is a multi-billion dollar, top-ten listed pharmaceutical company in Japan with a diverse portfolio of pharmaceutical products. DSP aims to produce innovative pharmaceutical products in the psychiatry and neurology, which is designated as a key therapeutic area, as well as oncology. DSP has more than 7,000 employees worldwide.

 

PolyActiva raises AUD$9.2M in Series B venture funding to boost clinical trials for intraocular implants to treat glaucoma.


PolyActiva announced today that it has raised AUD $9.2 Million in a Series B financing round from a consortium of investors including the Medical Research Commercialisation Fund (MRCF) and Brandon Biosciences Fund 1 (BBF1) (both managed by Brandon Capital), Yuuwa Capital and additional participation from angel investors.

PolyActiva said the funds will be used to further the preclinical and clinical development programs of its products under development, including an intra-ocular implant to treat glaucoma, an intra-ocular implant to treat severe infections of the eye and an intra-articular product to treat osteoarthritis.

PolyActiva’s proprietary drug-polymer conjugate technology enables sustained release, site-specific drug delivery from products with different physical forms, including rods, films, fibers and gels, substantially broadening its potential applications.  The drug-polymer conjugates are able to carry high drug loads, which allow therapeutic quantities of drug to be delivered over extended periods of time from a very small implant.  At the end of therapy, the polymer is designed to erode completely leaving no residue, which facilitates its chronic use and repeat administration and obviates the need for removal of the implant at the end of therapy. PolyActiva has proven the technology in validated animal models for delivery of drugs to the posterior region of the eye.

Polyactiva’s development portfolio includes both low risk products that deliver established drugs to a proven site of action, which abbreviates the product registration process, and also high value products that deliver novel drugs to treat clinically unmet needs.

This funding follows PolyActiva’s Series A round, which was completed in 2011.

About PolyActiva Pty Ltd
PolyActiva is a pioneering biotechnology company developing drug-polymer conjugates that allow for site specific drug delivery from medical device components such as ocular implants, intra-articular gel implants, and drug-eluting fibers. The Company has developed a novel and scalable manufacturing process that can easily be adapted to existing device component production processes, providing greater flexibility over the composition of the final material. Using this process, PolyActiva has built drug-polymer conjugates from a number of drug candidates with different chemical structures and linkage points and has also developed a number of functional co-monomers and polymer segments. The Company has completed proof of concept studies on these and is working towards developing first products. PolyActiva is interested in hearing from medical technology companies interested in incorporating PolyActiva’s drug eluting components in their devices. PolyActiva was founded in 2011 as a joint venture between CSIRO and the Bionic Ear Institute and is located in Melbourne, Australia.

Roche buys rights to Israeli Chiasma's PhIII rare disease drug in $595M deal


Roche and Chiasma announce collaboration to develop and commercialize Chiasma’s Octreolin® for acromegaly and neuroendocrine tumors

Facial aspect of a patient with acromegaly. The cheekbones are pronounced, the forehead bulges, the jaw is enlarged and facial lines prominent. Souce: Wikimedia Commons

Roche  and Chiasma privately held biopharma company, announced today that they have entered into an agreement to develop and commercialize Chiasma’s proprietary product Octreolin, initially for acromegaly and subsequently for neuroendocrine tumors. Octreolin is an investigational oral form of the peptide octreotide, a somatostatin analog that is commercially available only by injection.  Octreolin is currently in a pivotal phase 3 clinical trial for acromegaly.

Under the terms of the agreement, Roche received a worldwide exclusive license to Octreolin, and will assume responsibility for the commercialization of Octreolin. Genentech will market the product in the United States after US FDA approval. Chiasma will continue development through completion of the pivotal phase 3 clinical trial for acromegaly. The arrangement includes an upfront payment to Chiasma of $65 million, future considerations of up to $530 million in development and commercial milestones, as well as tiered, double-digit royalties on Octreolin net sales.

Commenting on the deal, Fredric D. Price, Chiasma’s Chairman and Chief Executive Officer said: “We are especially pleased to have entered into this agreement with Roche, an ideal collaboration partner that has the right development and commercial resources in the areas of endocrinology and oncology to support Octreolin.”

Hal Barron, M.D., Roche Global Head of Product Development and Chief Medical Officer added: “If approved, Octreolin would be an important alternative for patients with acromegaly, a disorder that develops when a person’s pituitary gland produces too much growth hormone. Octreolin is an investigational oral regimen that avoids the painful injections of current treatment options.”

About Chiasma

Chiasma is developing oral drugs that previously were only available by injection, thereby providing patients with pain-free medications that are self-administered. The Company’s lead candidate is an oral form of the peptide octreotide, initially being developed for patients with acromegaly that is in a phase 3 (pivotal) trial.  Chiasma is evaluating additional proteins, peptides and small molecules that can be applied to its proprietary Transient Permeability Enhancer (TPE) technology to enable oral delivery of drugs that previously were available by injection only.  Chiasma is a Delaware corporation with a 100% owned Israeli subsidiary.

Allergan buys migraine drug developer MAP Pharmaceuticals for $958 million


Acquisition Enhances Allergan Leadership Position in Neurology and Migraine Specialty

Through our dedicated employees at MAP Pharmaceuticals, we have made tremendous progress to date with our lead product candidate, LEVADEX®, enabling us to realize substantial value for our stockholders through this transaction," said Timothy S. Nelson, President and Chief Executive Officer, MAP Pharmaceuticals

Through our dedicated employees at MAP Pharmaceuticals, we have made tremendous progress to date with our lead product candidate, LEVADEX®, enabling us to realize substantial value for our stockholders through this transaction,” said Timothy S. Nelson, President and Chief Executive Officer, MAP Pharmaceuticals

Allergan, Inc. (NYSE:AGN) and MAP Pharmaceuticals, Inc. (Nasdaq: MAPP) today jointly announced that they have entered into a definitive merger agreement whereby Allergan will acquire 100% of the shares of MAP Pharmaceuticals for a price of $25.00 per share. MAP Pharmaceuticals is a biopharmaceutical company focused on developing and commercializing new therapies in Neurology, including LEVADEX®, an orally inhaled drug for the potential acute treatment of migraine in adults. LEVADEX® is currently under review with the U.S. Food and Drug Administration (FDA).

The transaction, which has been unanimously approved by the boards of directors of both companies, will be accomplished pursuant to a cash tender offer followed by a second step merger. The per share cash offer price represents a 60% premium over MAP’s closing stock price on the Nasdaq Stock Market of $15.58 on January 22, 2013, and represents a total equity value of approximately $958 million, on a fully-diluted basis. The acquisition is expected to close late in the first quarter or in the second quarter of 2013.

One of the key drivers of Allergan’s continued success is our focus on medical specialties where we have extensive knowledge of physician and patient needs, and can provide a broad portfolio of products,” said David E.I. Pyott, Chairman of the Board, President and Chief Executive Officer, Allergan.

“One of the key drivers of Allergan’s continued success is our focus on medical specialties where we have extensive knowledge of physician and patient needs, and can provide a broad portfolio of products,” said David E.I. Pyott, Chairman of the Board, President and Chief Executive Officer, Allergan. “Allergan has a record of leadership in the Neurosciences field and, according to a recent physician survey, is now perceived as the #1 company in prophylactic migraine management by physicians. During the past few years, Allergan has received regulatory approvals in 56 countries for BOTOX® for use in the treatment of chronic migraine. As a result, thousands of patients who suffer from chronic migraine have benefited from this important treatment option. We plan to capitalize on this depth of expertise in Neurology as we continue the global development of LEVADEX® as a potential acute treatment for migraine that is complementary to BOTOX® and use MAP’s proprietary drug particle and inhalation technologies to generate new pipeline opportunities.”

“Through our dedicated employees at MAP Pharmaceuticals, we have made tremendous progress to date with our lead product candidate, LEVADEX®, enabling us to realize substantial value for our stockholders through this transaction,” said Timothy S. Nelson, President and Chief Executive Officer, MAP Pharmaceuticals. “We are pleased that we and Allergan share similar values and a common vision in neuroscience that make for a strong cultural and scientific fit between our companies. We believe this acquisition by our partner Allergan will increase the potential for our product candidates to make a meaningful difference for patients we have worked so hard to serve.”

In January 2011, Allergan entered into a collaboration agreement with MAP to co-promote LEVADEX®, contingent upon potential regulatory authority approvals in the U.S. and Canada, to neurologists and pain specialists in these markets. In May 2011, MAP initially submitted a New Drug Application (NDA) for LEVADEX® to the FDA. In October 2012, MAP resubmitted its NDA, which included additional data and provided responses to FDA comments. In November 2012, MAP announced that its NDA resubmission for LEVADEX® was accepted for filing by the FDA and that the FDA has classified the resubmission as a complete Class 2 response and has set a goal date of April 15th, 2013 under the Prescription Drug User Fee Act (PDUFA).

Assuming this transaction closes as planned, and approval of LEVADEX® occurs on or before the PDUFA date of April 15th, 2013, Allergan anticipates that this transaction will be dilutive to 2013 earnings per share by approximately $0.07 and accretive to earnings per share by the second half of 2014. Allergan will provide 2013 guidance on its February 5, 2013 earnings call. Allergan currently anticipates that, excluding this transaction, 2013 earnings per share growth expectations will fall within our mid-teens growth aspiration.

Allergan expects to fund the transaction with a combination of cash on hand, cash equivalents and short-term borrowings under its commercial paper program. The transaction is not subject to any financing contingency.

 

Alexion buys Enobia: $610M in cash and $470 M in future milestones


Leonard Bell, Alexion CEO

Alexion Pharmaceuticals, Inc. and Enobia Pharma Corp. today announced that the companies have signed a definitive agreement under which Alexion will acquire 100% of the capital stock of Enobia. Enobia is a private biopharmaceutical company based in Montreal, Canada and Cambridge, Massachusetts, which is focused on the development of therapies to treat patients with ultra-rare and life-threatening genetic metabolicdisorders.

Enobia’s lead product candidate ENB-0040 (asfotase alfa), is a human recombinant targeted alkaline phosphatase enzyme-replacement therapy for patients suffering with hypophosphatasia (HPP), an ultra-rare, life-threatening, genetic metabolic disease for which there are no approved treatment options. Alexion will acquire full worldwide development and commercial rights to asfotase alfa. Asfotase alfa was awarded orphan drug designation in the U.S. and EU in 2008 and Fast Track status in the U.S. in 2009, and is currently in Phase II clinical development.

“Hypophosphatasia is an ultra-rare and life-threatening disease, and those patients who survive live with debilitating morbidities including skeletal deformity, severe muscle weakness, and progressive damage to vital organs,” said Leonard Bell, M.D., Chief Executive Officer of Alexion. “Asfotase alfa has shown very compelling Phase II clinical data in infants and juveniles with hypophosphatasia. The acquisition of Enobia is very well aligned with Alexion’s objective to develop and deliver life-transforming therapies for patients suffering with ultra-rare, severe, and life-threatening disorders.”

Alexion has proven expertise in developing and commercializing therapies to transform the lives of patients with severe and ultra-rare disorders, making them the ideal partner to advance the work of the Enobia team and bring asfotase alfa to HPP patients around the world.

Dr. Robert Heft, President and Chief Executive Officer of Enobia.

Dr. Robert Heft, President and Chief Executive Officer of Enobia.

“Enobia and our scientific collaborators have developed an elegant compound showing very promising clinical results to date,” said Dr. Robert Heft, President and Chief Executive Officer of Enobia. “Together with Alexion, we share a sharp focus on transforming the lives of patients with severe and ultra-rare disorders. The hypophosphatasia patient community will be well served by the experience and international scope of Alexion.”

The Transaction

Alexion will acquire Enobia in an all-cash transaction. Under the terms of the agreement, Alexion has agreed to pay $610 million in cash upon consummation of the transaction, and up to $470 million in cash to be paid upon achievement of various regulatory and sales milestones. Alexion is not issuing equity in connection with the acquisition. The transaction is subject to customary conditions, including the expiration or termination of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act. The Boards of both companies have approved the transaction and the companies currently anticipate that the transaction will be completed in the first quarter of 2012.

Alexion intends to finance the acquisition through cash on hand and $300 million of committed bank debt.

Goldman, Sachs & Co. is acting as financial advisor to Alexion. Ropes and Gray LLP is acting as legal counsel to Alexion. Bank of America Merrill Lynch is acting as financial advisor to Enobia. WilmerHale is acting as legal advisor to Enobia.

About Hypophosphatasia (HPP)

HPP is an ultra-rare, genetic, and life-threatening metabolic disease characterized by defective bone mineralization and impaired phosphate and calcium regulation leading to progressive damage to multiple vital organs including destruction and deformity of bones, profound muscle weakness, seizures, impaired renal function, and respiratory failure.(1,2,3,4) The severe manifestations of the genetic deficiency in HPP affect people of all ages, and approximately 50 percent of infants with the disease do not survive past one year of age.(1)

HPP is caused by a genetic deficiency of an enzyme known as tissue non-specific alkaline phosphatase (TNSALP), which causes life-long abnormalities in metabolism of the two vital minerals calcium and phosphate, leading directly to the debilitating morbidities and premature mortality of the disease.(1) There are currently no therapies approved for HPP.(1)

About Asfotase Alfa

Asfotase alfa is an investigational, highly innovative, first-in-class recombinant protein that addresses the underlying cause of HPP by targeting replacement of the missing enzyme to the necessary body tissues. Asfotase alfa is designed to normalize the genetically defective metabolic process and prevent or reverse the severe and life-threatening complications of life-long dysregulated mineral metabolism in patients with HPP.

2012 Initial Financial Outlook

Alexion will provide 2012 financial guidance in February, including one-time expenses related to the Enobia acquisition. 2012 non-GAAP research and development expenses are expected to transiently rise to approximately 20 to 21% of sales, due to activities associated with Enobia’s programs, and then to return to the Company’s target of approximately 17% to 18% of sales in 2013. Non-GAAP selling, general and administrative expenses associated with the proposed acquisition are expected to have limited impact in 2012.

Alexion is reiterating all areas of 2011 guidance provided in its third quarter 2011 earnings announcement in October.

.

About Enobia Pharma Corp.

Enobia Pharma Corp., based in Montreal, Canada, and Cambridge, Massachusetts, is a privately held clinical stage biotech company focused on developing novel therapeutics for serious metabolic bone disorders. The Company’s largest investors include OrbiMed, Fonds de Solidarite des Travailleurs du Quebec (F.T.Q.), Capital Regional et Cooperatif Desjardins, CTI Life Sciences Fund, L.P., and Lothian Partners 27 (Sarl) SICAR.

About Alexion

Alexion Pharmaceuticals, Inc. is a biopharmaceutical company focused on serving patients with severe and ultra-rare disorders through the innovation, development and commercialization of life-transforming therapeutic products. Alexion is the global leader in complement inhibition, and has developed and markets Soliris(R) (eculizumab) as a treatment for patients with PNH and aHUS, two debilitating, ultra-rare and life-threatening disorders caused by chronic uncontrolled complement activation. Soliris is currently approved in more than 35 countries for the treatment of PNH, and in the United States and the European Union for the treatment of aHUS. Alexion is evaluating other potential indications for Soliris and is pursuing development of other innovative biotechnology product candidates in early stages of development.

Gilead Sciences to Acquire Pharmasset, Inc. for $11 Billion


Gilead Sciences, Inc. and Pharmasset, Inc. announced today that the companies have signed a definitive agreement under which Gilead will acquire Pharmasset for $137 per share in cash. The transaction, which values Pharmasset at approximately $11 billion, was unanimously approved by Pharmasset’s Board of Directors. Gilead plans to finance the transaction with cash on hand, bank debt and senior unsecured notes. The company expects the transaction, when completed, to be dilutive to Gilead’s earnings through 2014 and accretive in 2015 and beyond. Further guidance will be provided when the transaction closes, which is expected to be in the first quarter of 2012.

Pharmasset currently has three clinical-stage product candidates for the treatment of chronic hepatitis C virus (HCV) advancing in trials in various populations.gilead

  • The company’s lead product candidate, PSI-7977, an unpartnered uracil nucleotide analog, has recently been advanced into two Phase 3 studies in genotype 2 and 3 patients. Both studies will utilize 12 weeks of treatment with PSI-7977 in combination with ribavirin. One study will compare this all-oral regimen against 24 weeks of the standard-of-care pegylated interferon/ribavirin in treatment-naïve patients, and the second study will compare the all-oral regimen to placebo in interferon-intolerant/ineligible patients. A third Phase 3 study in genotype 1 patients will be initiated in the second half of 2012, the design of which is dependent on the outcome of Phase 2 studies which are evaluating PSI-7977 in various combinations in genotype 1-infected patients. If successful, this strategy could lead to an initial U.S. regulatory approval of PSI-7977 in 2014.
  • PSI-938, an unpartnered guanosine nucleotide analog, is being tested in a Phase 2b interferon-free trial as monotherapy and in combination with PSI-7977 in subjects with HCV of all viral genotypes.
  •  Mericitabine (RG7128), a cytidine nucleoside analog, is partnered with Roche and is being evaluated in three Phase 2b trials. Roche is responsible for all aspects of the development of mericitabine.

“The acquisition of Pharmasset represents an important and exciting opportunity to accelerate Gilead’s effort to change the treatment paradigm for HCV-infected patients by developing all-oral regimens for the treatment of the disease regardless of viral genotype,” said John C. Martin, PhD, Chairman and Chief Executive Officer of Gilead. “

Pharmasset presented compelling Phase 2 data earlier this month further characterizing the strong efficacy and safety profile of PSI-7977. The compound, together with Pharmasset’s other pipeline candidates, represents a strong strategic fit with Gilead’s vision, pipeline and capabilities. This transaction will serve to drive the long-term growth of our business, and we look forward to working closely with the Pharmasset team to advance a broad clinical program in HCV to address the unmet needs of patients and the medical community.”

“We are excited to join together with Gilead, which shares our commitment to providing HCV patients with new, highly efficacious and safe oral therapies,” said Schaefer Price, President and Chief Executive Officer, Pharmasset.

“We are very encouraged by the data from our Phase 2 studies of PSI-7977 and believe strongly in the potential of this compound to be a component in the transformation of the treatment of chronic HCV. Gilead’s established expertise and leadership in the field of antiviral drug development and commercialization, coupled with the company’s existing portfolio of promising compounds for HCV, make this partnership an ideal step to fully realize the potential of our promising molecules as part of future all-oral combination therapies for millions of patients in need around the world.”

Gilead’s research and development portfolio includes seven unique molecules in various stages of clinical development for the treatment of HCV. Pegylated interferon in combination with ribavirin is currently part of the standard of care treatment for patients with chronic hepatitis C. Gilead is focused on advancing multiple compounds with different mechanisms of action and resistance profiles in combinations that will support delivery of an all-oral regimen that would eliminate the need for pegylated interferon. Three separate all-oral Phase 2 studies are currently ongoing, and Gilead expects clinical data from these studies to become available in 2012 and early 2013. Pharmasset’s compounds are complementary to Gilead’s existing HCV portfolio, and the transaction will help advance Gilead’s effort to develop an all-oral regimen for the treatment of HCV.

GlycoMimetics and Pfizer Enter into Licensing Agreement for Drug Candidate for $340 M


GlycoMimetics and Pfizer Enter into Licensing Agreement for Drug Candidate Currently in Development to Treat Patients Experiencing Vaso-occlusive Crisis Associated with Sickle Cell Disease

GlycoMimetics, Inc. announced  that it has entered into an exclusive worldwide licensing agreement with Pfizer Inc. Pfor the GlycoMimetics investigational compound GMI-1070. GMI-1070 is a pan-selectin antagonist currently in Phase 2 development for the treatment of vaso-occlusive crisis associated with sickle cell disease. GMI-1070 has received Orphan Drug and Fast Track status from the U.S. Food and Drug Administration (FDA).

Vaso-occlusive crisis, which can last five to six days on average, results in over 75,000 hospitalizations each year in the U.S. These crises cause pain and tissue damage leading to multiple organ damage, a requirement for life-long narcotic pain medications, and eventually to significantly shorter life spans. While the genetic and molecular cause of sickle cell disease has been known for more than 50 years, therapy for painful crises has not significantly advanced. GMI-1070 is thought to inhibit selectin interactions, a key early step in the inflammatory process leading to vaso-occlusive crisis. In preclinical studies, GMI-1070 restored blood flow to affected vessels of sickle cell animals experiencing vaso-occlusive crisis.

“We are very pleased to partner with Pfizer for the advancement of GlycoMimetics’ lead drug candidate, GMI-1070, which is initially being evaluated in patients with sickle cell disease experiencing vaso-occlusive crisis. This is a major unmet medical need,” said Rachel King, CEO of GlycoMimetics. “We value the resources and experience that Pfizer brings to the program, and recognize that the agreement is an important validation of GlycoMimetics’ unique chemistry expertise in discovery of proprietary drug candidates.”

Under the terms of the agreement, Pfizer will receive an exclusive worldwide license to GMI-1070 for vaso-occlusive crisis associated with sickle cell disease and for other diseases for which the drug candidate may be developed. GlycoMimetics will remain responsible for completion of the ongoing Phase 2 trial under Pfizer’s oversight, and Pfizer will then assume all further development and commercialization responsibilities. The potential value of the agreement for GlycoMimetics is approximately $340 million, including an upfront payment as well as development, regulatory and commercial milestones. GlycoMimetics is also eligible for royalties on any sales.

“Pfizer is committed to helping improve the lives of patients with rare diseases, and we see potential for GlycoMimetics’ GMI-1070 to be a significant advance in the treatment of vaso-occlusive crisis of sickle cell disease,” said Yvonne Greenstreet, senior vice president and head of the Medicines Development Group within Pfizer’s Specialty Care business unit. “This experimental compound and partnership are emblematic of our strategy in rare disease, targeting areas of high unmet need to deliver improved patient outcomes.”

“This partnership is an important milestone for GlycoMimetics as the company advances its clinical development program,” added Jim Barrett, Ph.D., Chairman of the Board of GlycoMimetics and General Partner, New Enterprise Associates. “It’s a testament to the progress made to date with GMI-1070, and will enhance continued development of this potential treatment for patients suffering from vaso-occlusive crisis.”

About GMI-1070

GMI-1070 is a rationally designed glycomimetic inhibitor of E-, P- and L-selectins that interferes in a key early step in the inflammatory process leading to leukocyte adhesion and recruitment to inflamed tissue. GMI-1070 has shown activity in several models of diseases in which leukocyte adhesion and activation play a key role.

GMI-1070 is initially being developed for the treatment of vaso-occlusive crisis associated with sickle cell disease. By inhibiting selectin interactions, GMI-1070 may be able to decrease the enhanced cell adhesion that results in vaso-occlusive crisis. In preclinical studies, GMI-1070 restored blood flow to affected vessels of sickle cell animals experiencing vaso-occlusive crisis. Two Phase 1 trials of GMI-1070 were successfully completed in the first quarter of 2009, with no serious adverse events reported. The program is currently in Phase 2 clinical testing. GMI-1070 is also being evaluated in preclinical studies for the treatment of other diseases, including hematologic malignancies, where selectin-mediated cell adhesion and migration is known to play a key role in the disease process.

Issued U.S. patents cover GMI-1070 with additional intellectual property issued and pending outside the U.S.

About Sickle Cell Disease and Vaso-Occlusive Crisis

Vaso-occlusive crisis is the main clinical feature of sickle cell disease, causing severe pain, often resulting in significant patient complications, and sometimes death. Currently, there are no mechanism-based therapies for treatment of vaso-occlusive crisis. Treatment consists primarily of supportive therapy in the form of hydration and pain control, typically requiring hospitalization for five to six days.

About GlycoMimetics, Inc.

GlycoMimetics is a privately held biotechnology company that capitalizes on advances in the field of glycobiology. The company uses rational design of small molecule drugs that mimic the functions of bioactive carbohydrates to develop new drug candidates. The company’s initial focus is on therapeutics to treat orphan conditions in which inflammation and cell adhesion may play a key role.

Arrowhead Research Corporation Acquires Roche RNA Assets and Site


Arrowhead Research Corporation, today announced that it has acquired RNA therapeutics assets from Roche (including the state-of-the-art research site in Madison, WI.

“This acquisition is transformational for us and important to the broader RNAi field,” said Dr. Christopher Anzalone, President and CEO of Arrowhead. “The combination of these assets and Arrowhead’s existing RNAi technologies results in what we believe to be the broadest RNAi therapeutics company in the world, with unparalleled delivery solutions and licenses granting broad freedom to operate within the three primary siRNA formats.”

The Roche assets and IP acquired by Arrowhead include:

— Roche Madison Inc. (formerly Mirus Bio Corporation,), providing an advanced proprietary RNAi delivery platform known as Dynamic PolyCunjugates(TM) (DPCs);

— License from Tekmira Pharmaceuticals Corp. for proprietary SNALP RNAi delivery;

— Proprietary Liposomal Nanoparticle (LNP) RNAi delivery system developed by Roche;

— License from Alnylam providing access to Alnylam’s RNAi IP and Canonical siRNA structures;

— License from City of Hope providing access to Dicer substrate siRNA structures;

— License from MDRNA (now Marina Biotech) providing access to Meroduplex siRNA structures;

— A team of over 40 leading scientists in the RNAi field and state-of-the-art facilities and infrastructure in Madison, WI.

As a result of the transaction, Arrowhead now has an array of additional delivery technologies that complement its existing delivery platforms, access to the three primary siRNA formats, and the infrastructure and team necessary to create new RNAi therapeutics and drive large industry partnerships.

Under the terms of the agreement, Roche transferred to Arrowhead all of its existing RNAi operations and research facilities in Madison, Wisconsin along with its employees, equipment, related technology licenses and intellectual property covering current and planned development programs. Roche obtained a minority stake in Arrowhead as well as rights to negotiate for certain future products, milestone payments and royalties on sales.

Dr. Anzalone continued; “Together with our technologies from Calando and Leonardo, we now have five RNAi delivery systems. We believe this transaction positions Arrowhead as the leader in delivery, which remains the limiting factor of therapeutic RNAi. We have the platforms to optimize delivery based on tissue type, disease state, target, and siRNA chemistry. In addition, we now have broad access to use the three primary siRNA structures: Canonical, Dicer, and Meroduplex. No other company has the ability to optimize efficiency by optimizing the type of siRNA format in this way, and this is extremely powerful.”

Arrowhead also closed on $4 million of new funding in addition to the $6 million financing that was recently announced, providing approximately $10 million of capital. In addition, the Company entered into an agreement with Lincoln Park Capital (LPC) to provide up to $15 million to support the new operations. Under the LPC agreement, Arrowhead may, subject to customary conditions, draw all or part of the $15 million commitment at its sole discretion over a three-year period. There are no warrants associated with the facility and pricing is based on closing market prices. “This provides Arrowhead with an efficient means to minimize dilution to shareholders by bringing in equity capital in a relatively inexpensive way and only if/when necessary,” said Dr. Anzalone.

“Ever since starting Calando, we have been committed to making gene silencing via RNAi a real and powerful new modality in medicine,” Dr. Anzalone continued. “Acquiring three new delivery technologies gives us even greater flexibility and substantially more power across multiple disease areas. For instance, the Madison team has developed multiple generations of the DPC technology and generated large amounts of small animal and non-human primate data. We have not seen any RNAi delivery technology with better efficiency or tolerability. The Madison team is second to none and we are thrilled to welcome them to Arrowhead. In addition, the new RNAi chemistry IP moves Arrowhead from being a force in delivery to being a complete RNAi drug developer and partner. Together, these factors put our business on stronger and broader footing than ever before. We have the ability and plan to develop our own pipeline of RNAi drugs and to become financially self-sufficient by entering into multiple partnerships. As large pharmaceutical companies are increasingly choosing to outsource RNAi development because of the delivery challenge, we are uniquely positioned to compete for partnerships that could bring substantial non-dilutive capital. Our model is to use this revenue to finance operations and the development of our own portfolio of RNAi drugs. These collaborations are also intended to drive longer-term value as partners’ drug candidates trigger milestone payments and royalties. This acquisition is truly transformational.”

Transaction Highlights:

— Strategic Acquisition. This establishes Arrowhead as a fully integrated RNAi therapeutics developer.

— Delivery Leadership. Arrowhead acquired three advanced siRNA delivery technologies with substantial animal data.

— Broad Access to RNAi IP. Arrowhead now has a comprehensive portfolio of RNAi IP, providing broad freedom to operate and, therefore, flexibility in designing therapeutics.

— World-Class Team and Facilities. Experienced team in Madison that works in state-of-the-art facilities.

— Partnership/Revenue Opportunities. The combination of technologies, IP, and capabilities enable earlier-stage and larger partnership opportunities with biotech and pharmaceutical companies, providing a path towards profitability.

— Integration into Arrowhead. This acquisition serves as the cornerstone of Arrowhead’s transition over the last year from a diversified nanotechnology company to a pure-play, fully enabled nanomedicine company.

Over the coming weeks and months, Arrowhead will be providing additional information on the new technologies. In addition, as the operations are integrated, Arrowhead will provide guidance on clinical timelines, partnering plans, and budgets.

About Arrowhead Research Corporation

Arrowhead Research Corporation  is a nanomedicine company developing innovative therapies at the interface of biology and nanoengineering to cure disease and improve human health. Arrowhead addresses its target markets through focused subsidiaries, which include: Calando Pharmaceuticals, a leader in delivering small RNAs for gene silencing; Ablaris Therapeutics, an anti-obesity therapeutics company; and Nanotope, a regenerative medicine company.

Cubist Pharmaceuticals to Acquire Adolor for up to $415 M


ACQUISITION ADDS FIRST-IN-CLASS HOSPITAL PRODUCT ENTEREG(R)AND PROMISING LATE-STAGE COMPOUND ADL5945 LEXINGTON, Mass. & EXTON, Pa.

Cubist Pharmaceuticals, Inc.  and Adolor Corporation today announced that they have signed a definitive agreement under which Cubist will acquire all of the outstanding shares of Adolor for $4.25 per share in cash, or approximately $190 million on a fully-diluted basis, net of Adolor’s third quarter 2011 cash balance. In addition to the upfront cash payment, each Adolor stockholder will receive one Contingent Payment Right (CPR), entitling the holder to receive additional cash payments of up to $4.50 for each share they own if certain regulatory approvals and/or commercialization milestones for ADL5945 are achieved. The total transaction is valued at up to $415 million, net of Adolor’s third quarter 2011 cash balance, and is expected to be accretive in 2012.

Under the agreement, Cubist will commence a tender offer to purchase all of the outstanding shares of Adolor for the upfront cash payment and a CPR. The transaction, which has been unanimously approved by the Boards of Directors of both companies, is expected to close in the fourth quarter of 2011.

Adolor markets ENTEREG(R) (alvimopan), the first and only FDA-approved therapy to accelerate the time to upper and lower gastrointestinal recovery following partial large or small bowel resection surgery with primary anastomosis. ENTEREG is an oral, peripherally-acting mu opioid receptor antagonist. Cubist, with its focus on addressing acute care and hospital needs, will leverage its existing commercial operations to promote ENTEREG. Launched in 2008, ENTEREG generated more than $25 million in U.S. sales in 2010 and $15.7 million through June 30, 2011. Cubist anticipates peak ENTEREG sales of over $100 million annually.

Adolor’s lead development program is ADL5945, an oral, peripherally-restricted mu opioid receptor antagonist. It is currently in development for the treatment of chronic opioid induced constipation (OIC), a growing, multi-billion dollar, currently underserved market. Adolor announced positive Phase 2 data for ADL5945 in August 2011 and Phase 3 trials are expected to be initiated in 2012. Cubist plans to retain certain U.S. and specialty rights while seeking a partner to assist with ex-U.S. and primary care commercialization.

“This transaction is an excellent strategic fit for Cubist and the latest milestone in what has been a transformational year for the company,” said Cubist President and Chief Executive Officer Michael Bonney. “ENTEREG is a first-in-class therapy with strong growth potential, and we believe our experienced sales force and strong commercial platform will realize the potential of this important hospital product. With the addition of ADL5945, Cubist will have a truly outstanding late-stage pipeline with three strong candidates addressing significant markets. We are excited about the acquisition of Adolor and believe it will deliver significant value to our shareholders, hospital customers, and patients.”

Michael Dougherty, Adolor’s President and Chief Executive Officer, stated, “This transaction delivers significant immediate value to Adolor stockholders, as well as potential future value through the CPRs. Cubist shares our commitment to patients and their health care providers, and we expect that ENTEREG and ADL5945 will benefit from Cubist’s proven track record and larger platform in development and commercialization.”

Terms of the CPR call for additional cash payments of up to $4.50 per CPR. The CPR will entitle each Adolor stockholder to receive up to $3.00 per share if ADL5945 receives regulatory approval in the U.S. and up to $1.50 per share if ADL5945 receives regulatory approval in the European Union, in both instances prior to July 1, 2019. In each case, the size of the payment would depend on the parameters of the approval. The CPR will not be publicly traded.

 

 

Bristol-Myers Squibb AcquireS Amira Pharmaceuticals for $325 M upfront and additional $150 M in milestones


Acquisition Marks Bristol-Myers Squibb’s Entrance into Fibrotic Diseases, an Area of High Unmet Need that is Complementary to Current Therapeutic Areas of Focus

Bristol-Myers Squibb Company  and Amira Pharmaceuticals, Inc., announced today that the companies have signed a definitive agreement under which Bristol-Myers Squibb will acquire privately held Amira Pharmaceuticals, a small-molecule pharmaceutical company focused on the discovery and early development of new drugs to treat inflammatory and fibrotic diseases.

Under the terms of the agreement, Bristol-Myers Squibb will acquire all of Amira Pharmaceuticals’ issued and outstanding shares of capital stock and stock equivalents in an all-cash transaction for a purchase price of $325 million upfront and potential additional milestone payments totaling $150 million. Bristol-Myers Squibb will secure Amira Pharmaceuticals’ fibrosis program, including the lead asset AM152, an orally available lysophosphatidic acid 1 (LPA1) receptor antagonist which has completed Phase I clinical studies and is now poised for Phase IIa proof-of-confidence studies for the treatment of idiopathic pulmonary fibrosis (IPF) and systemic sclerosis (SSc), or scleroderma. Bristol-Myers Squibb will also obtain Amira Pharmaceuticals’ preclinical autotaxin program, which may be useful in the treatment of neuropathic pain and cancer metastases. Bristol-Myers Squibb plans to retain Amira Pharmaceuticals’ scientists who work on both of these programs and they will remain located in San Diego.

“As part of the continued execution of our focused BioPharma strategy, Bristol-Myers Squibb has identified fibrotic diseases as an area of high unmet medical need that complements our research efforts in several of our therapeutic areas,” said Elliott Sigal, executive vice president, chief scientific officer and president, Research and Development, Bristol-Myers Squibb. “The acquisition of Amira Pharmaceuticals represents the latest example of our String of Pearls strategy, a highly targeted set of transactions designed to enrich our innovative pipeline with potential medicines to help patients in need.”

The closing of the transaction is subject to customary regulatory approvals.

“We are pleased to have Bristol-Myers Squibb acquire Amira Pharmaceuticals. Our LPA and autotaxin programs are world leading and will be in excellent hands,” stated Bob Baltera, chief executive officer, Amira Pharmaceuticals. “It has been a pleasure to work with Bristol-Myers Squibb throughout this highly competitive process.”

“Amira Pharmaceuticals’ scientists have been leaders in the research and development of lysophosphatidic acid receptor antagonists for fibrosis,” said Jeremy Levin, senior vice president, Strategy, Alliances and Transactions. “We compliment the professional approach of the investors and Amira Pharmaceuticals’ leadership and scientific team who, since 2005, have built a highly innovative company. We will now build on that history and commitment to innovation to discover and develop novel medicines in this important disease area.”

About Amira Pharmaceuticals

Founded in 2005 and headquartered in San Diego, Amira Pharmaceuticals is a small molecule pharmaceutical company focused on the discovery and early development of new drugs to treat inflammatory and fibrotic diseases. Amira combines the rigor of a big pharmaceutical company with the ingenuity and energy of a small company, creating an environment for efficient development of novel compounds and effective pre-clinical and clinical program decisions. Our team is building on unparalleled insights into bioactive lipid pathways and complex signaling processes controlling many conditions including asthma, chronic obstructive pulmonary disease, cardiovascular and various fibrotic diseases. Amira has a partnership with GlaxoSmithKline for the development of FLAP (5-lipoxygenase activating protein) inhibitors in respiratory and cardiovascular disease.

Merck buys Inspire Pharmaceuticals for $430 M


Merck will acquire Inspire, a specialty pharmaceutical company focused on developing and commercializing ophthalmic products.

Merck (NYSE:MRK), known as MSD outside the United States and Canada, and Inspire Pharmaceuticals, Inc. (NASDAQ: ISPH) today announced that they have entered into a definitive agreement under which Merck will acquire Inspire, a specialty pharmaceutical company focused on developing and commercializing ophthalmic products.

Under the terms of the agreement, Merck, through a subsidiary, will commence a tender offer for all outstanding common stock of Inspire at a price of $5.00 per share in cash, a 26 percent premium to the closing price of Inspire’s common stock on April 4, 2011. The transaction has a total cash value of approximately $430 million. The transaction has been unanimously approved by the boards of directors of both companies and Inspire’s board recommended that the company’s shareholders tender their shares pursuant to the tender offer. In addition, Warburg Pincus Private Equity IX, L.P., which owns approximately 28 percent of the outstanding shares of Inspire, has agreed to tender all of its shares into the offer.

Merck continues to build upon its long-term commitment to improving therapeutic options for the treatment of eye diseases, said Beverly Lybrand, senior vice president and general manager, neuroscience and ophthalmology, Merck

In March, 2011, Merck announced that the New Drug Application (NDA) for SAFLUTAN® (tafluprost), an investigational preservative-free prostaglandin analogue ophthalmic solution, had been accepted for standard review by the U.S. Food and Drug Administration (FDA). SAFLUTAN is the proposed trade name for tafluprost in the United States.

“As one of the world’s leading healthcare companies, Merck is the ideal partner to enhance the long-term potential of Inspire’s portfolio of ophthalmic assets. We are delighted that Merck recognized the strength of an integrated platform leveraging the growing AZASITE® (azithromycin ophthalmic solution) 1% product opportunity and the strong relationships within the ophthalmic community cultivated by our high quality, specialty eye care sales force in the U.S.,” said Adrian Adams, president and CEO of Inspire. “Based upon an extensive analysis of various strategic options, as I have outlined since we announced the results of the TIGER-2 Phase 3 clinical trial, we believe this combination provides a compelling and timely opportunity for our shareholders to realize the value of their investment in Inspire.”

The closing of the tender offer will be subject to certain conditions, including the tender of a number of Inspire shares that, together with shares owned by Merck, represent at least a majority of the total number of Inspire’s outstanding shares (assuming the exercise of all options and vesting of restricted stock units), the expiration of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act and other customary conditions. Upon the completion of the tender offer, Merck will acquire all remaining shares through a second-step merger.

Yale and Gilead Sciences Announce $100 M Cancer Research Collaboration


Gilead Sciences, Inc. (Nasdaq:GILD) and Yale School of Medicine today announced the formation of a multi-year research collaboration focused on the discovery of novel cancer therapies.

The research effort will initially span four years with an option to renew for up to ten years. Gilead will provide $40 million in research support and basic science infrastructure development during the initial four-year period, and will provide a total of up to $100 million over ten years should the collaboration be extended through that timeframe. Gilead will have the first option to license Yale inventions that result from the collaboration.

Yale and Gilead will develop a multi-disciplinary research program to search for the genetic basis and underlying molecular mechanisms of many forms of cancer. Scientists from both organizations will work together to identify new molecular targets that provide better understanding of the basis of disease and enable development of novel targeted therapies, including new therapies that overcome drug resistance that develops in some cancer patients treated with current targeted therapies.

“The collaboration brings together one of the world’s top research universities and a biopharmaceutical company dedicated to addressing unmet medical needs with the goal of finding new treatments for cancer,” Yale President Richard C. Levin said. “This truly is transformative support that leverages the Yale Cancer Center’s top scientists, our West Campus technology investments and the resources of the new Smilow Cancer Hospital. I can’t think of a better partner to have in this collaboration than Gilead.”

“Following Gilead’s recent acquisitions of cancer development programs, this partnership serves to strengthen our discovery capabilities in the area of oncology,” said Norbert W. Bischofberger, Ph.D., Gilead’s Executive Vice President, Research and Development and Chief Scientific Officer. “Based on the strong track-record of the Yale cancer research team, I am confident this collaboration will lead to important advances in the understanding of the genetic basis of cancer as we collectively seek to develop novel targeted therapies for patients in areas of unmet medical need.”

Research projects will be chosen by a joint steering committee to be chaired by Joseph Schlessinger, Ph.D., and chair of Yale’s Department of Pharmacology and director of the Cancer Biology Institute at West Campus.

“When we find cancer targets that are new, we will work with Gilead on designing drugs, which they can then test in the clinic,” Schlessinger said. “This is a tremendous opportunity for Yale and Gilead.”

The Yale science team will also include Dr. Thomas Lynch, Director, Yale Cancer Center, Physician-in-Chief, Smilow Cancer Hospital at Yale-New Haven Hospital and renowned for his work in personalized treatments for cancer patients.

The Yale Center for Genome Analysis at West Campus, headed by Richard Lifton, M.D., Ph.D., chair of the Department of Genetics, will analyze the DNA of a variety of tumor types to look for genetic mutations associated with cancers. Schlessinger’s team will use the data to understand effects of the gene mutations on cancer and to identify ways to intervene in the disease process, such as indentifying small molecules that will serve as the basis of new cancer therapies.

“Yale’s faculty in this partnership possess critical and complementary skills that comprise an optimal team for cancer drug development,” according to Robert Alpern, M.D., Dean of the Yale School of Medicine. “Tom Lynch brings experience in clinical cancer trials, Rick Lifton has been a leading innovator in genetics and genomics, and Yossi Schlessinger has unparalleled success in cancer drug development.”

About Yale School of Medicine

For more than fifty years, Yale School of Medicine has been at the forefront of the continuously evolving field of cancer research. The Yale Cancer Center is one of a select network of 41 comprehensive cancer centers in the nation designated by the National Cancer Institute and the only comprehensive center in southern New England, whose mission encompasses basic and clinical research, cancer prevention and control, patient care, community outreach and education.

About Gilead Sciences

Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company’s mission is to advance the care of patients suffering from life-threatening diseases worldwide. Headquartered in Foster City, California, Gilead has operations in North America, Europe and Asia Pacific.

Dainippon Sumitomo Pharma and Intercept Pharmaceuticals Announce Agreement worth $315 M to Develop and Commercialize Obeticholic Acid (INT-747) for Chronic Liver Disease


Dainippon Sumitomo Pharma Co, Ltd. (DSP) and Intercept Pharmaceuticals, Inc. (Intercept) today announced that they have entered into an exclusive licensing agreement for the development and commercialization of Intercept’s first-in-class FXR agonist obeticholic acid (OCA, also known as INT-747). DSP will advance OCA in Japan and China for the treatment of chronic liver diseases, with an initial focus on primary biliary cirrhosis (PBC) and nonalcoholic steatohepatitis (NASH). Intercept is currently preparing for the initiation of a Phase III PBC program in the US and Europe and, under the company’s cooperative research and development agreement (CRADA) with the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), a large placebo-controlled trial of OCA in NASH patients recently started enrolling in the US.
Under the terms of the licensing agreement, Intercept will receive an initial payment from DSP of $15 million and will be eligible to receive approximately $300 million in additional milestone payments associated with the successful development and commercialization of OCA. Upon launch of OCA, Intercept will be entitled to receive tiered double-digit royalties from DSP based on sales in its territory. DSP has the exclusive option to add several other Asian countries to its territory, including Korea and Taiwan, and to pursue additional indications. DSP will be responsible for the costs of developing and commercializing OCA in its territory.
“OCA is an important strategic addition to our growing pipeline of hepatology drugs and reflects DSP’s strong commitment to specialty therapeutic areas,” said Masayo Tada, President and CEO of DSP. “There is a very high unmet medical need in the hepatology area in Asia and DSP’s marketed products SUMIFERON®, a natural alpha interferon, and MIRIPLA®, a therapeutic agent for hepatocellular carcinoma, benefit many thousands of liver patients in Japan. We strongly believe that OCA has the potential to significantly add to the treatment options DSP can make available to these patients and are looking forward to working with Intercept to bring OCA to the market as an important new therapy for PBC and the first drug approved for NASH.”
“This agreement is an important milestone for our OCA program and provides additional confirmation of our drug’s potential,” said Mark Pruzanski, MD, President and CEO of Intercept. “We are excited to be partnering in Asia with DSP, given its proven track record in the development and commercialization of drugs in the hepatology area. This collaboration with DSP will provide important development support as we advance OCA in parallel for PBC, NASH and possibly other indications.”
About Obeticholic Acid (OCA or INT-747)
OCA is a potent, first-in-class farnesoid X receptor (FXR) agonist derived from the primary human bile acid chenodeoxycholic acid, the natural endogenous FXR agonist. Intercept has previously announced positive Phase II results from randomized clinical trials in patients with primary biliary cirrhosis (PBC) and in type 2 diabetics with nonalcoholic fatty liver disease. The clinical data and mechanism of action support OCA’s potential as a novel, hepatoprotective agent in a broad range of chronic liver diseases.
About Primary Biliary Cirrhosis (PBC)
PBC is the most common autoimmune chronic liver disease that primarily afflicts women over the age of 40. PBC causes substantial loss of intrahepatic bile ducts, resulting in impaired bile flow (cholestasis) and progressive fibrosis that leads eventually to cirrhosis. It is estimated that there are approximately 50,000 PBC patients in Japan and more than 400,000 in China. Given inadequate treatment options, up to 50% of such patients worldwide continue to be at significant risk of progression to liver transplant or death.
About Nonalcoholic Steatohepatitis (NASH)
NASH is a more serious form of nonalcoholic fatty liver disease (NAFLD) and occurs in patients who drink little or no alcohol. NASH occurs most commonly in obese and insulin resistant patients, but is also seen in lean individuals. In a report of a 5-10 year follow-up study, up to 25% of NASH patients progressed to cirrhosis of the liver. The prevalence of NASH in Japan is estimated to be at least 1% of the adult population and pediatric disease is also becoming more common, while in the US it is estimated that 3-5% of the population has the disease in association with higher obesity rates. There is currently no approved treatment for NASH.

About Intercept Pharmaceuticals, Inc.

Intercept is a biotechnology company focused on discovering and developing small molecule drugs for the treatment of chronic liver and metabolic diseases.  The company’s most advanced programs are focused on the development of modified bile acids that are selective for FXR, a nuclear receptor, and TGR5, a G protein-coupled receptor. Bile acid signaling through these receptors regulates key aspects of lipid, glucose and overall energy metabolism, while also serving to maintain the functional integrity of the liver, intestine and kidneys, organs that are exposed to bile acid flux.

About Dainippon Sumitomo Pharma Co., Ltd. (DSP)

DSP is a multi-billion dollar, top-ten listed pharmaceutical company in Japan with a diverse portfolio of pharmaceutical products. DSP aims to produce innovative pharmaceutical products in the central nervous system (CNS) field and other specialty areas. Today, DSP has more than 7,000 employees worldwide.

Kerentech and Suanfarma agreement at the Spanish Economic Press.


Please click on the picture to see it in full screen.
[issuu viewmode=presentation layout=http%3A%2F%2Fskin.issuu.com%2Fv%2Fcolor%2Flayout.xml backgroundcolor=FFFFFF documentid=110215135720-2240cb7b501d44619b0b33416d5a1810 docname=negocio_150211 username=EstherMoscatel loadinginfotext=Suanfarma%20y%20Keren%20Partners%20logran%20un%20acuerdo%20de%20inversion showhtmllink=false tag=suanfarma width=550 height=778 unit=px]

New pathway for antidepressants: Berkeley Lab new fluorescent assay reveals TREK1 mechanism


Ehud Isacoff, Professor of Neurobiology and Chair, Graduate Group in Biophysics at Berkeley

Using a unique and relatively simple cell-based fluorescent assay they developed, scientists with the U.S. Department of Energy (DOE)’s Lawrence Berkeley National Laboratory (Berkeley Lab) and the University of California (UC), Berkeley have identified a means by which fluoxetine, the active ingredient in Prozac, suppresses the activity of the TREK1 potassium channel. TREK1 activity has been implicated in mood regulation and could be an important target for fluoxetine and other antidepressant drugs.

“Whereas the inhibiting of serotonin re-uptake remains fluoxetine’s primary antidepression mechanism, many pharmacological agents have more than one target,” says Ehud Isacoff, a neurobiophysicist who holds joint appointments with Berkeley Lab’s Physical Biosciences Division and UC Berkeley’s Department of Molecular and Cell Biology. “Our study shows that the inhibition of TREK1 by fluoxetine, which was found in earlier studies, is accompanied by an unbinding of the protein’s C-terminal domain from the membrane. This is the first observation of the mechanism by which TREK1 might be regulated by antidepressant drugs.”

Isacoff is the corresponding author on a paper reporting the results of this study that appears in the Proceedings of the National Academy of Sciences (PNAS). The paper is titled “Optical probing of a dynamic membrane interaction that regulates the TREK1 channel.” Co-authoring this paper were Guillaume Sandoz, a TREK1 specialist with France’s National Center for Scientific Research at the Institute for Molecular and Cellular Physiology, and PhD student Sarah Bell, both of whom were with Isacoff’s research group at the time the work was done.

Neurons in the human brain are like high-speed transistors, controlling the flow of electrical current through channels in their membranes by the opening and closing of molecular “gates” that control the flow of ions through selective pores. TREK1 is one of the most ubiquitous of these transmembrane proteins, gating the passage of potassium ions through neural membranes, which sets the excitability of the neuron. Earlier studies had shown that when the TREK1 gene is “knocked out” of mice, the mice display a depression-resistant phenotype that mimics the behavior of mice treated with fluoxetine and that the antidepressant inhibits the activity of the TREK1 channel. While these results pointed to a possible role for the TREK1 ion channel in the beneficial response to fluoxetine, the mechanism behind this activity was unclear.

“Studying what the different protein parts of an ion channel do is a huge challenge,” Isacoff says. “Over the years, my group has developed techniques by which the domains of channel proteins can be labeled with site-specific fluorescent dyes. Structural rearrangements of the labeled sites in the channel can then be detected through changes in the fluorescence.”

Isacoff and his group separated the C-terminal domain from the rest of the protein and tagged it with a green fluorescent protein (GFP) – a fluorescent protein from jellyfish commonly used to paint cells green for biological studies. Whereas the pore of the TREK1 ion channel is embedded in the plasma membrane of a neuron, the C-terminal is a short tail that protrudes out into the surrounding cytoplasm.

Using voltage clamps to measure electrical currents through the channel and fluorescence to monitor the disposition of the C-terminal domain, Isacoff and his group found that when the C-terminal tail is fully bound to the plasma membrane, the TREK1 potassium channel opens more; when the tail is unbound from the plasma membrane, the ion channel tends to close.

“We found that fluoxetine causes the isolated C-terminal domain to unbind from the membrane and also causes an inhibition of current from the full TREK1 channel,” Isacoff says.

The next step will be to see how the C-terminal tail is affected by the presence of fluoxetine when the tail is still attached to the rest of the TREK1 protein. In the meantime, Isacoff and his team feel they now have a valuable assay that can be used to monitor the reversible plasma membrane association of protein domains without the need for scanning, optical slicing or imaging.

“Pharmaceutical companies screening for potential new drugs, such as improved antidepressants, prefer assays that are fast and simple,” Isacoff says. “Our technique can be used to follow changes in lipid composition that result from membrane signaling events, or to study the binding to membranes by cytoplasmic regulatory domains of ion channels. This could be very useful for pharmaceutical research.”

###

This research was primarily supported by the National Institutes of Health.

Lawrence Berkeley National Laboratory is a U.S. Department of Energy (DOE) national laboratory managed by the University of California for the DOE Office of Science. Berkeley Lab provides solutions to the world’s most urgent scientific challenges including sustainable energy, climate change, human health, and a better understanding of matter and force in the universe. It is a world leader in improving our lives through team science, advanced computing, and innovative technology. Visit our Website at www.lbl.gov

Mindfulness meditation training changes brain structure in 8 weeks


Mass. General-led study shows changes over time in areas associated with awareness, empathy, stress

Participating in an 8-week mindfulness meditation program appears to make measurable changes in brain regions associated with memory, sense of self, empathy and stress. In a study that will appear in the January 30 issue of Psychiatry Research: Neuroimaging, a team led by Massachusetts General Hospital (MGH) researchers report the results of their study, the first to document meditation-produced changes over time in the brain’s grey matter.

“Although the practice of meditation is associated with a sense of peacefulness and physical relaxation, practitioners have long claimed that meditation also provides cognitive and psychological benefits that persist throughout the day,” says Sara Lazar, PhD, of the MGH Psychiatric Neuroimaging Research Program, the study’s senior author. “This study demonstrates that changes in brain structure may underlie some of these reported improvements and that people are not just feeling better because they are spending time relaxing.”

Previous studies from Lazar’s group and others found structural differences between the brains of experienced mediation practitioners and individuals with no history of meditation, observing thickening of the cerebral cortex in areas associated with attention and emotional integration. But those investigations could not document that those differences were actually produced by meditation.

For the current study, MR images were take of the brain structure of 16 study participants two weeks before and after they took part in the 8-week Mindfulness-Based Stress Reduction (MBSR) Program at the University of Massachusetts Center for Mindfulness. In addition to weekly meetings that included practice of mindfulness meditation – which focuses on nonjudgmental awareness of sensations, feelings and state of mind – participants received audio recordings for guided meditation practice and were asked to keep track of how much time they practiced each day. A set of MR brain images were also taken of a control group of non-meditators over a similar time interval.

Meditation group participants reported spending an average of 27 minutes each day practicing mindfulness exercises, and their responses to a mindfulness questionnaire indicated significant improvements compared with pre-participation responses. The analysis of MR images, which focused on areas where meditation-associated differences were seen in earlier studies, found increased grey-matter density in the hippocampus, known to be important for learning and memory, and in structures associated with self-awareness, compassion and introspection. Participant-reported reductions in stress also were correlated with decreased grey-matter density in the amygdala, which is known to play an important role in anxiety and stress. Although no change was seen in a self-awareness-associated structure called the insula, which had been identified in earlier studies, the authors suggest that longer-term meditation practice might be needed to produce changes in that area. None of these changes were seen in the control group, indicating that they had not resulted merely from the passage of time.

“It is fascinating to see the brain’s plasticity and that, by practicing meditation, we can play an active role in changing the brain and can increase our well-being and quality of life.” says Britta Hölzel, PhD, first author of the paper and a research fellow at MGH and Giessen University in Germany. “Other studies in different patient populations have shown that meditation can make significant improvements in a variety of symptoms, and we are now investigating the underlying mechanisms in the brain that facilitate this change.”

Amishi Jha, PhD, a University of Miami neuroscientist who investigates mindfulness-training’s effects on individuals in high-stress situations, says, “These results shed light on the mechanisms of action of mindfulness-based training. They demonstrate that the first-person experience of stress can not only be reduced with an 8-week mindfulness training program but that this experiential change corresponds with structural changes in the amydala, a finding that opens doors to many possibilities for further research on MBSR’s potential to protect against stress-related disorders, such as post-traumatic stress disorder.” Jha was not one of the study investigators.

James Carmody, PhD, of the Center for Mindfulness at University of Massachusetts Medical School, is one of co-authors of the study, which was supported by the National Institutes of Health, the British Broadcasting Company, and the Mind and Life Institute.

Celebrating the 200th anniversary of its founding in 1811, Massachusetts General Hospital is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of nearly $700 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, systems biology, transplantation biology and photomedicine.

The brain eliminates childhood fear memories during adolescence


The brain is able to eliminate during adolescence memories linked to fear acquired years ago , according to a U.S. team discoveries ,published in PNAS . Authors suggest that, in adulthood, these memories can be recovered, when living a similar  situation.

Francis S. Lee, Associate Professor. Department of Psychiatry and Pharmacology of Weill Cornell Medical College,

Some of the fear memories  acquired in the first years of life are removed temporarily during adolescence, according to the findings of a study conducted by a team from Cornell University in New York. Francis S. Lee, of Weill Cornell Medical College is the lead author of the article  published today in Proceedings of the National Academy of Sciences.

In tests on mice, researchers have worked on the similarities of the neural circuitry between humans and animals in order to understand the molecular and behavioral processes related to emotional learning during adolescence. A number of studies in mice in pre-and post-adolescent age, revealed that the acquisition, storage and retrieval of memories related to fear varies with the stage of brain development.

When mice move into adolescence, these memories are deleted. But the authors have discovered that these memories can be recovered recover if a situation similar to that related to the creation of memory  is lived again, provided the animal is already in adulthood.

Amygdala and hippocampus
Specifically, Lee and his group have determined that the temporary suppression of fear during adolescence is directly related to two types of change in brain activity. On the one hand, there are alterations in synaptic activity in a region of the amygdala that is, in turn, linked to the processing of fear. In addition, the molecular signaling in the hippocampus, a region responsible for the recovery of these emotions, is damaged.

The cause of these processes are, in the case of the amygdala, synaptic changes, whereas in the case of the hippocampus are the routes of PI3K and MAPK signaling that act as emotional rearrangement trigger.

There are changes in synaptic activity in the amygdala and molecular changes in  the hippocampus signaling caused by PI3K and MAPK

Specific plasticity
The authors suggest that this line of research could provide a therapeutic approach to emotional disorders such as PTSD and specific phobias. Determine, as did the team of Lee, there is a unique form of brain plasticity when fear is part of learning, will facilitate the understanding of endogenous mechanisms used in the management of unwanted memories.

(PNAS 2010, DOI: 10. 1073.pnas.1012975108).

MicroRNA Prostate Cancer Stem Cells and Metastasis


UT MD Anderson preclinical research boosts case for new drug approach

Dean Tang, Ph.D., professor in MD Anderson’s Department of Molecular Carcinogenesis.

A small slice of RNA inhibits prostate cancer metastasis by suppressing a surface protein commonly found on prostate cancer stem cells. A research team led by scientists at The University of Texas MD Anderson Cancer Center reported today in an advance online publication at Nature Medicine.

“Our findings are the first to profile a microRNA expression pattern in prostate cancer stem cells and also establish a strong rationale for developing the microRNA miR-34a as a new treatment option for prostate cancer,” said senior author Dean Tang, Ph.D., professor in MD Anderson’s Department of Molecular Carcinogenesis.

MicroRNAs, or miRNAs, are short, single-stranded bits of RNA that regulate the messenger RNA expressed by genes to create a protein.

Cancer stem cells are capable of self-renewal, have enhanced tumor-initiating ability and are generally more resistant to treatment than other cancer cells. They are associated with tumor recurrence and metastasis, the lethal spreading of cancer to other organs.  These capacities are more prevalent in cancer cells that feature a specific cell surface protein called CD44, Tang said.

“CD44 has long been linked to promotion of tumor development and, especially, to cancer metastasis,” Tang said. “Many cancer stem cells overexpress this surface adhesion molecule. Another significant finding from our study is identifying CD44 itself as a direct and functional target of miR-34a.”

MicroRNA goes up, CD44 and cancer stem cells fall

In a series of lab experiments with cell lines, human xenograft tumors in mice and primary human prostate cancer samples, the researchers demonstrated that miR-34a inhibits prostate cancer stem cells by suppressing CD44.

  • miR-34a is greatly reduced in prostate cancer cells that express high levels of CD44 on the cell surface. In 18 human prostate tumors, the microRNA was expressed at 25 to 70 percent of the levels found in cells without CD44.
  • Prostate tumors in mice that also received miR-34a treatment were one third to half the average size of those in control group mice.
  • In CD44-positive prostate cancer cell lines, treatment with miR-34a resulted in greatly reduced tumor incidence. Most dramatically, in one cell line, tumor regeneration was blocked in all 10 treated animals, while tumors formed in all 10 animals treated with the control miRNAs.
  • Many characteristics of cancer stem cells – formation of self-renewing cells, clonal growth capacity and formation of spheres – were suppressed when miR-34a was overexpressed in prostate cancer cell lines.
  • Most significantly, intravenous treatment of tumor-bearing mice with synthetic miR-34a reduced tumor burden by half in one tumor type. It also steeply reduced lung metastases in another tumor type, resulting in increased animal survival.
  • Interestingly, the researchers observed a consistent, inverse relationship between miR-34a levels and CD44, the surface marker used to enrich prostate cancer stem cells. For example, the CD44 protein and CD44-expressing cancer cells were reduced in tumors treated with the microRNA.  Tumors with miR-34a blocked had higher levels of CD44 protein and messenger RNA.
  • Finally, knocking down CD44 with a short hairpin RNA produced the same results as treating cells with miR-34a did – reduced tumor development, tumor burden and metastases.

“There are many companies developing microRNA-based drugs,” Tang said. “Delivery of miRNAs is a challenge, but the field is moving fast through the preclinical stage.”

Scientists from Austin-based Mirna Therapeutics collaborated on the study.  Mirna has eight microRNAs in preclinical development, including miR-34a.

The project was funded in part by grants from the National Cancer Institute and the National Institute of Environmental Health Science, the U.S. Department of Defense and the Elsa Pardee Foundation.

Co-authors were first author Can Liu, Bigang Liu, M.D., Xin Chen, Tammy Calhoun-Davis, Hangwen Li, Ph.D., Hong Yan, Ph.D., Collene Jeter, Ph.D., and Sofia Honorio, Ph.D., all of MD Anderson’s Department of Molecular Carcinogenesis at the Science Park in Smithville, Texas; Can Liu and Xin Chen are also students in The University of Texas Graduate School of Biomedical Sciences at Houston, jointly operated by MD Anderson and The University of Texas Health Science Center at Houston;  Lubna Patrawala, Ph.D., Kevin Kelnar, Jason Wiggins, Andreas Bader, Ph.D., and David Brown, Ph.D., all of Mirna Therapeutics, Inc. and Randy Fagin, M.D., of The Hospital at Westlake, Austin, Texa

Being Poor Can Suppress Children’s Genetic Potentials, Texas Universty Study says.


Growing up poor can suppress a child’s genetic potential to excel cognitively even before the age of 2, according to research from psychologists at The University of Texas at Austin. The end of poverty

Half of the gains that wealthier children show on tests of mental ability between 10 months and 2 years of age can be attributed to their genes, the study finds.

But children from poorer families, who already lag behind their peers by that age, show almost no improvements that are driven by their genetic makeup.

The study of 750 sets of twins by Assistant Professor Elliot Tucker-Drob does not suggest that children from wealthier families are genetically superior or smarter. They simply have more opportunities to reach their potential. These findings go to the heart of the age-old debate about whether “nature” or “nurture” is more important to a child’s development.

They suggest the two work together and that the right environment can help children begin to reach their genetic potentials at a much earlier age than previously thought. “You can’t have environmental contributions to a child’s development without genetics. And you can’t have genetic contributions without environment,” says Tucker-Drob, who is also a research associate in the university’s Population Research Center.

“Socioeconomic disadvantages suppress children’s genetic potentials.” The study, published in the journal Psychological Science, was co-authored by K. Paige Harden of The University of Texas at Austin, Mijke Rhemtulla of The University of Texas at Austin and the University of British Columbia, and Eric Turkheimer and David Fask of the University of Virginia.

The researchers looked at test results from twins who had taken a version of the Bayley Scales of Infant Development at about 10 months and again at about 2 years of age. The test, which is widely used to measure early cognitive ability, asks children to perform such tasks as pulling a string to ring a bell, putting three cubes in a cup and matching pictures. At 10 months, there was no difference in how the children from different socioeconomic backgrounds performed. By 2 years, children from high socioeconomic background scored significantly higher than those from low socioeconomic backgrounds.

In general, the 2-year-olds from poorer families performed very similarly to one another. That was true among both fraternal and identical twins, suggesting that genetic similarity was unrelated to similarities in cognitive ability. Instead, their environments determine their cognitive success.

Among 2-year-olds from wealthier families, identical twins (who share identical genetic makeups) performed very similarly to one another. But fraternal twins were not as similar — suggesting their different genetic makeups and potentials were already driving their cognitive abilities. “Our findings suggest that socioeconomic disparities in cognitive development start early,” says Tucker-Drob.

“For children from poorer homes, genetic influences on changes in cognitive ability were close to zero. For children from wealthier homes, genes accounted for about half of the variation in cognitive changes.”

The study notes that wealthier parents are often able to provide better educational resources and spend more time with their children but does not examine what factors, in particular, help their children reach their genetic potentials. Tucker-Drob is planning follow-up studies to examine that question. For more information, contact: Gary Susswein, College of Liberal Arts, 512 471 4945; Elliot Tucker-Drob.

Israel Chief Scientist Office awards Oramed with a NIS 2.9M Grant


Oramed Pharmaceuticals Inc.(OTCBB: ORMP.OB) (www.oramed.com), a developer of oral delivery systems, today reported that its wholly owned Israeli subsidiary, Oramed Ltd., was awarded a government grant amounting to a total net amount of NIS 2.9 million ($807,000 USD), from the Office of the Chief Scientist (OCS) at the Ministry of Industry, Trade and Labor of Israel.

The OCS awards grants to industry in Israel in order to foster technological innovations. The funds will be designated and used by Oramed Ltd. to support further R&D and clinical study of its Oral Insulin capsule and Oral GLP1- Analog.

Nadav Kidron Esq., CEO of Oramed Pharmaceuticals, commented: “We are pleased to have received the support of the Office of the Chief Scientist for the second year in a row. This grant will allow for further development of our product pipeline.”

About the Office of the Chief Scientist and its Grant Application Criteria

The OCS selects its recipients on various criteria including the financial strength of a company, the exceptionality of a company’s innovative technology, and the potential of a company’s technology to significantly improve an existing product or process.

Gilead buys Arresto for $225 M


Gilead Sciences, Inc. (Nasdaq:GILD) and Arresto Biosciences, Inc., a privately-held, development-stage biotechnology company focused on arrestomedicines to treat fibrotic diseases and cancer, today announced the signing of a definitive agreement pursuant to which Gilead will acquire Arresto.

Under the terms of the agreement, Gilead will acquire Arresto for $225 million and potential future payments based on achievement of certain sales levels. Gilead anticipates that the deal would close in the first quarter of 2011, subject to satisfaction of certain closing conditions, and plans to finance the acquisition through available cash on hand. Arresto develops medicines that target enzymes involved in the synthesis of the extracellular matrix, which appear to play a role in the etiology of a variety of fibrotic diseases and cancer.gilead

The company’s lead product is AB0024, a humanized monoclonal antibody (mAb) targeting the human lysyl oxidase-like-2 (LOXL2) protein.

The company recently initiated a Phase I study evaluating AB0024 in patients with idiopathic pulmonary fibrosis (IPF).

A Phase I study of AB0024 in patients with advanced solid tumors is also ongoing.

“Arresto’s research and development expertise is well aligned with Gilead’s areas of focus, including our ongoing clinical program for ambrisentan in IPF,” said Norbert W. Bischofberger, PhD, Gilead’s Executive Vice President, Research and Development and Chief Scientific Officer. “We look forward to working with the team from Arresto to advance the development of novel therapies for serious fibrotic diseases and explore their potential for the treatment of tumors.” “Gilead shares Arresto’s vision of bringing innovative new therapeutic options to patients with unmet medical needs,” said Peter Van Vlasselaer, PhD, Arresto’s President and Chief Executive Officer. ”

Arresto was founded based on the promise of selective antibody therapies and I am confident the combined resources of our companies best position us to build upon our early scientific results.” “Under Peter’s direction, Arresto has accomplished a remarkable amount in three short years,” said Beth Seidenberg, MD, Arresto Chairman of the Board, and Partner at Kleiner Perkins Caufield & Byers. “Peter’s leadership is extraordinary and proven in several companies. The board is proud of the accomplishment of the Arresto team and enthusiastic about Gilead’s commitment to advancing the programs for the treatment of patients with fibrosis and cancer.”

Lundbeck enters into drug discovery collaboration with Zenobia and Vernalis


H. Lundbeck A/S (Lundbeck) today announced that it has signed agreements with Zenobia Therapeutics (Zenobia) and Vernalis plc (Vernalis) which will provide Lundbeck with access to know-how relevant for making inhibitors for Leucine-rich repeat kinases. A member of this family of kinases, the Leucine-rich repeat kinase 2 (LRRK2) is a high priority target for Lundbeck due to it’s relevance in several therapeutic indications, including Parkinson’s disease.

Lundbeck will collaborate with Zenobia and utilize Zenobia’s expertise in protein expression and x-ray crystallography for the LRRK2 target. Under the agreement, Zenobia will complete x-ray crystal structures of wild-type and a Parkinson’s disease associated mutant in complex with Lundbeck lead compounds. Zenobia retains all rights and ownership of the LRRK2 structure and to their internal LRRK2 chemistry program. The financial terms of this collaboration are not disclosed.

The Vernalis agreement will focus on a drug discovery collaboration utilising Vernalis’ fragment and structure-based drug discovery platform. Under the terms of the agreement, Lundbeck and Vernalis will collaborate in identifying candidate compounds that can inhibit LRRK2. Vernalis will receive fees and a potential share in the downstream success of the product in the form of milestones and royalties on sales. The financial terms of this collaboration are not disclosed.

These collaborations are important supplements to Lundbeck’s commitment to provide new innovative medicines in the CNS field in areas with high unmet needs. They represent another step in Lundbeck’s new R&D strategy to ensure we have the most efficient platform for the future discovery and development of drugs that will be able to help and treat biologically defined groups of patients with brain diseases. It is this type of drugs we expect will be in demand in the future“, says Peter Høngaard Andersen, Executive Vice President, Research Management at Lundbeck.

LRRK2, also known as dardarin, is an enzyme that is encoded by the LRRK2 gene[i]. Mutations in this gene represent one of the risk factors for the development of Parkinson’s disease[ii]. Four LRRK2 gene variants found are found in the familial Parkinson’s cases, but infrequent in the general population. LRRK2 inhibition potentially has neuroprotective

i] Neuron, Volume 44, Issue 4, 595-600, 18 November 2004

[ii] Nature Reviews Neuroscience, Volume 11, 791, December 2010

Evotec and MedImmune ink Metabolic disease alliance worth €254


·         Focus on innovative diabetes therapydiabetes-education-190x155

·         €5 million upfront payment, up to €254 million milestones and royalties

·         Evotec’s first commercial agreement in the field of beta cell regeneration

Evotec AG (Frankfurt Stock Exchange: EVT, TecDAX) today announced that via its subsidiary Develogen AG it has entered into a license and collaboration agreement with MedImmune (the global biologics unit of AstraZeneca), in the diabetes therapeutic area, with a particular focus on the regeneration of insulin producing beta cells.  The license gives MedImmune exclusive access to a portfolio of research programs and represents the first deal executed by Evotec on beta cell regeneration assets and capabilities.

The agreement triggers an upfront payment of € 5 million.  Further on, additional deferred payments including potential milestone payments of up to € 254 million as well as royalties are agreed.  The milestone payments will be due upon achievement of certain clinical as well as regulatory and commercial events.  Further milestone payments may be achieved with the approval of additional indications and programs.  Evotec will also receive research payments to support further in vivo and in vitro pharmacology efforts conducted in collaboration with MedImmune.

Dr Cord Dohrmann, Chief Scientific Officer of Evotec, commented: “The loss of insulin producing beta cells is tightly linked to the development of diabetes.  Using a unique screening approach for beta cell regeneration targets, we have identified and validated novel and highly relevant biological factors.  The most advanced factor has demonstrated efficacy in animal models of beta cell regeneration in particular increasing the functional beta cell mass and thereby improving and restoring glycemic control.”  Dr. Dohrmann continued: “MedImmune is a leader in biopharmaceutical research with cutting edge protein production and engineering capabilities and thus a perfect partner for Evotec.  Together we intend to generate a pipeline of biological factors that have the potential to prevent or reverse disease progression, and confer optimal glycemic control in patients. “

Merck to Acquire SmartCells, Inc. in a deal worth up to $500m.


Merck & Co., Inc., (NYSE:MRK) and SmartCells, Inc., today announced that they have entered into a definitive agreement under which Merck will acquire SmartCells, a private company developing a glucose responsive insulin formulation for the treatment of diabetes mellitus.Diabetes

Maintaining control of blood glucose levels represents a daily challenge for people living with diabetes,” said Nancy Thornberry, senior vice president and head, diabetes and obesity franchise, Merck Research Laboratories.

“Through the acquisition of SmartCells we have obtained innovative technology that may enable us to develop glucose-responsive insulins. If this investigational technology is ultimately approved for use with patients, it could provide an important new therapy for the treatment of diabetes. This holds the potential to significantly impact the treatment of this disease.”

Under the terms of the agreement, Merck will acquire all outstanding stock of SmartCells, Inc. In return SmartCells shareholders will receive an upfront cash payment and be eligible to receive clinical development and regulatory milestones for products resulting from the transaction for potential aggregate payments in excess of $500 million. Sales-based payments for products resulting from the transaction will also be payable. SmartCells’ board of directors has unanimously approved the transaction.

Teva to Acquire Theramex, Merck KGaA’s European Based Women’s Health Business


Acquisition Will Provide Teva with a Strong Platform to Expand its Global Women’s Health Business

theramexTeva Pharmaceutical Industries Ltd. (Nasdaq: TEVA) and Merck Serono, a division of Merck KGaA (FRA: MRK) announced today that they have entered into a definitive agreement under which Teva will acquire Theramex and related companies from Merck Serono.

Theramex offers a wide variety of women’s health products sold in 50 countries worldwide and had revenues of approximately 100 million euros in 2009, including sales in the countries in which Teva will acquire distribution rights. A significant portion of its revenues are derived from direct sales in France and Italy, where Theramex has developed strong brand recognition and a reputation for quality among women’s health specialists. As part of the agreement, Teva will also have distribution rights for Theramex’s products in certain countries including Spain and Brazil. The company’s tevapipeline includes a new oral contraceptive based on natural estrogens, NOMAC/E2, which has successfully completed phase III studies and submitted for approval in Europe. Theramex’s operations are supported by an accomplished R&D team and a cost-effective API facility, which produces most of the company’s API needs.

Commenting on today’s transaction, Shlomo Yanai, Teva’s President and Chief Executive Officer, said: “This is an important acquisition for Teva’s women’s health franchise. Theramex’s diversified product portfolio, its seasoned sales force and promising pipeline will be combined with the strong R&D capabilities and product portfolio of our U.S. women’s health business. Together the global team will accelerate the expansion of our women’s health franchise into key growth markets in Europe and around the world and provide an excellent springboard for future sales. We very much look forward to working together with Theramex’s experienced management team and having its work force join the Teva family.”

“Theramex has built a solid reputation in France and Italy as a company dedicated to women’s health and gynecology. As Theramex is entering the contraceptive market, we firmly believe that a combination with Teva will not only contribute to growing its position in the gynecological market but also to building a major player in the area of contraceptives.” said Elmar Schnee, Member of the Executive Board of Merck KGaA and President of the Merck Serono division.

Under the terms of the agreement, Teva will make a payment of 265 million euros at Closing. In addition, Merck Serono will be eligible to receive certain performance-based milestone payments. Teva will fund the acquisition from its internal resources. The transaction is subject to certain regulatory approval and is expected to close towards the end of this year or in early 2011.

McMaster University scientists turn skin into blood


Mick Bhatia

Mick Bhatia, scientific director of McMaster’s Stem Cell and Cancer Research Institute in the Michael G. DeGroote School of Medicine, and his team of researchers have discovered how to make human blood from adult human skin.

The discovery, published in the prestigious science journal Nature on Nov. 7, could mean that in the foreseeable future people needing blood for surgery, cancer treatment or treatment of other blood conditions like anemia will be able to have blood created from a patch of their own skin to provide transfusions. Clinical trials could begin as soon as 2012.

Mick Bhatia, scientific director of McMaster’s Stem Cell and Cancer Research Institute in the Michael G. DeGroote School of Medicine, and his team of researchers have also shown that the conversion is direct. Making blood from skin does not require the middle step of changing a skin stem cell into a pluripotent stem cell that could make many other types of human cells, then turning it into a blood stem cell.

“We have shown this works using human skin. We know how it works and believe we can even improve on the process,” said Bhatia. “We’ll now go on to work on developing other types of human cell types from skin, as we already have encouraging evidence.”

The discovery was replicated several times over two years using human skin from both the young and the elderly to prove it works for any age of person.

The research was funded by the Canadian Institutes of Health Research, the Canadian Cancer Society Research Institute, the Stem Cell Network and the Ontario Ministry of Research and Innovation.

Response to the discovery of the ability to turn human skin into human blood has been enthusiastic.

“CIHR is proud to invest in the excellent research that is being undertaken by Mick Bhatia’s laboratory at the Stem Cell and Cancer Research Institute at McMaster University,” said Alain Beaudet, president of the Canadian Institutes for Health Research.

“The Bhatia research effort is building on significant findings in recent years, which have shown that human skin cells can be reprogrammed into pluripotent cells that have the potential to become all cell types.

“The pioneering findings published today are the first to demonstrate that human skin cells can be directly converted into blood cells, via a programming process that bypasses the pluripotent stage. Producing blood from a patient’s own skin cells has the potential of making bone marrow transplant HLA matching and paucity of donors a thing of the past.”

Glen Murray, Ontario minister of research and innovation, said: “Future generations will benefit tremendously from the world-class research that Dr. Bhatia and Ontario stem cell scientists are making here today. Ontario is the place where stem cells were discovered. We will continue to lead the world with breakthrough discoveries that improve lives and create good jobs and a strong, innovative economy.”

Christine Williams, director of research for the Canadian Cancer Society Research Institute, saw the potential for cancer treatment.

“We are happy to be able to fund this important stem cell research which holds enormous promise for improved treatment of many types of cancer, including solid tumours and leukemias,” she said.

Cynthia Dunbar, head of the molecular hematopoiesis section of the U.S. National Institutes of Health’s National Heart, Lung and Blood Institute said: “Bhatia’s convincing demonstration that skin cells can be directly converted to hematopoietic progenitor cells is exciting and will immediately change the paradigms regarding the best way forward for production of hematopoietic cells to be used in regenerative medicine and in the study of human blood diseases.

“Bhatia’s approach detours around the pluripotent stem cell stage and thus avoids many safety issues, increases efficiency, and also has the major benefit of producing adult-type l blood cells instead of fetal blood cells, a major advantage compared to the thus far disappointing attempts to produce blood cells from human embryonic stem cells or induced pluripotent stem cells.”

Michael Rudnicki, director of the Stem Cell Network added: “This finding will no doubt be met with excitement in the research and medical communities.

“It’s been nearly 50 years since blood stem cells were first identified here in Canada and it’s fitting that this incredible new discovery should have happened here as well.”

Sam Weiss, professor and director of the Hotchkiss Brain Institute at the University of Calgary, said: “This groundbreaking work from Mick Bhatia’s lab is both fascinating and important. It heralds a new age by discovering a role for ‘directed differentiation’ in the treatment of cancers and other disorders of the blood and immune system.”

John Kelton, hematologist and dean and vice-president of health sciences for McMaster University said: “I find this discovery personally gratifying for professional reasons. During my 30 years as a practicing blood specialist, my colleagues and I have been pleased to help care for cancer patients whose lives were saved by bone marrow transplants. For all physicians, but especially for the patients and their families, the illness became more frustrating when we were prevented from giving a bone marrow transplant because we could not find a perfect donor match in the family or the community.

“Dr. Bhatia’s discovery could permit us to help this important group of patients.”

Amgen to Provide Testimony at FDA Hearing on Biosimilars


Joe Miletich, M.D., Ph.D., Amgen (Nasdaq: AMGN) Senior Vice President of Research and Development

Company Urges FDA to Put Patients First As Regulators Implement Biosimilar Pathway

Amgen (Nasdaq: AMGN) Senior Vice President of Research and Development Joe Miletich, M.D., Ph.D., will urge members of a U.S. Food and Drug Administration (FDA) panel charged with implementing a pathway for biosimilars to establish approval standards that ensure patient safety and follow a science-based approach.

“Put patients first and sound policy will follow,” Dr. Miletich said.  “Amgen believes biosimilars have a meaningful role to play in the health care system.  However, biosimilars—unlike generic drugs—are not identical to the innovative biological products.”  Getting the biosimilar pathway ‘right’ could benefit the future of biopharmaceuticals, whereas “imprudent policy” could simultaneously put patients unacceptably at risk, undermine the policy goals and set back the promise of new biologic treatments for patients.

Noting the complexities of biological products and the likely differences in products created from different living cells, Dr. Miletich will outline three key recommendations that the FDA should consider as it moves forward:

  1. Use well-designed clinical trials to establish biosimilarity;
  2. Ensure the product manufacturer and lot number is known for all administered biological; and
  3. Set scientific and practical criteria for interchangeability.

“The question before the agency is how we can minimize patient risk and uncertainty associated with the approval of biosimilars,” Dr. Miletich said.  “The challenge with biosimilars is knowing which structural variations matter clinically and which do not.  Many differences probably do not matter, while some differences are important.  Other differences remain open questions.  Clinical evaluations and experience are necessary to address these questions.”

Dr. Miletich added, “Minor changes in structure, formulation or impurities can have a significant impact on patients that cannot always be anticipated with analytical studies.”

Underscoring the need for clinical trials, Dr. Miletich stated, “In our 30 year history of making biologicals, we have achieved remarkable breakthroughs, developed complex proteins and supplied them to millions of patients in need.  However, in the process we have been humbled by unexpected clinical outcomes after analytical and preclinical studies predicted success.”

Dr. Miletich also noted that experience with biosimilar applications in Europe demonstrates the need for clinical trials.  Approximately half of the biosimilars developed in Europe have had unexpected clinical outcomes at some point in their development.  Clinical trials are an essential step in evaluating differences between medicines that analytical and pre-clinical studies indicate are similar.  Equally important, we must ensure accountability through accurate tracking and tracing of all biological products.

During his remarks, Dr. Miletich will express the need to continue evaluating products approved as biosimilars after they reach the market to ensure that subtle differences between biologics are well understood.  In his testimony, Dr. Miletich indicated that this would be particularly important prior to any biosimilar being approved as interchangeable, since such a determination may result in patients being repeatedly switched between products.

Dr. Miletich went on to say, “An interchangeability determination, if possible, would be very difficult to make and will require significant time and experience.  Interchangeability presents both scientific and public health challenges that would need to be addressed before such a determination could be made.”

Amgen believes that the agency should ensure that measures are in place to detect and limit the scope of harm from unexpected adverse events associated with use of any biological product.  These measures should include development and implementation of a pharmacovigilance system that provides accurate and comprehensive association and reporting of adverse events with the implicated product, as well as specific labeling to differentiate products that are biosimilar from those that are interchangeable to enable physicians to make informed treatment decisions.

In his concluding comments, Dr. Miletich urged the FDA to outline approval standards through a transparent and public process.  “Not all classes of biological products have the same level of complexity or risk, thus class-specific approval standards must be developed,” Dr. Miletich stated.  “Case-by-case approaches generate uncertainty leading to delays and increased cost.  Class-by-class standards are consistent with good review practices.  A public process for approval standards creates confidence among patients and physicians.”

On March 23, 2010, President Obama signed into law the Patient Protection and Affordable Care Act [1] which contained a provision authorizing the FDA to create an abbreviated approval pathway for biological products shown to be biosimilar to with an already FDA-approved biological medicine.  Several countries around the globe have already implemented approval pathways for biosimilars.  The European Union and Japan are among those that have successfully devised a set of science-based criteria to permit biosimilars in their jurisdictions.  With the FDA’s hearing on November 2-3, the United States is beginning the implementation process.

Dr. Miletich’s testimony was submitted in response to FDA’s notice [2] for public comments on an “Approval Pathway for Biosimilar and Interchangeable Biological Product.”  The deadline for submitted written comments is Dec. 31, 2010.

Protalix BioTherapeutics Announces Preliminary Top-Line Positive Data from taliglucerase alfa Switchover Trial


Protalix BioTherapeutics, Inc. (NYSE-AMEX: PLX, TASE: PLX), announced today positive preliminary data from the first 15 patients that completed the Company’s nine month, worldwide, multi-center, open-label, switchover trial of taliglucerase alfa for the treatment of Gaucher disease under a protocol cleared by the U.S. Food and Drug Administration (FDA).Protalix

The data indicate that patients can safely be switched to taliglucerase alfa from imiglucerase (Cerezyme(R)). Patients enrolled in the trial were switched from imiglucerase (doses ranging from 10-60 U/kg every other week) to an equivalent dose using the same number of units of taliglucerase alfa.

The data from the first 15 patients demonstrate that maintenance of efficacy was achieved over a nine month period with no increased safety concerns. Patients’ hemoglobin and platelet counts remained stable demonstrating hematological stability. As measured by MRI, mean spleen volume and liver volume also remained stable. There was no evidence of increased safety concerns in patients switched from Cerezyme(R) to taliglucerase alfa and there were no drug related serious adverse events. Hypersensitivity reactions were not reported in this patient group. One patient developed non-neutralizing IgG antibodies to taliglucerase at the end of the study. Detailed data will be presented at an upcoming medical meeting. The switchover trial was originally designed and cleared by FDA to enroll 15 patients, however, it was expanded to recruit a total of 30 patients as a result of the shortage of enzyme replacement therapy for Gaucher patients. Adult enrollment in the study has closed; pediatric enrollment remains open. “We are pleased with the interim results of the switchover trial to taliglucerase alfa,” said Dr. David Aviezer, the Company’s President and Chief Executive Officer. “Through our Phase III pivotal and extension trial, pediatric study in naïve patients, switch-over trial, expanded access and named patient programs, ATU program in France and supply agreement in Brazil, we are generating a robust clinical database for taliglucerase alfa.” Taliglucerase alfa is under review by the U.S. Food and Drug Administration with a Prescription Drug User Fee Action (PDUFA) date scheduled for February 25, 2011.

Immune Design closes $212M adjuvant pact with MedImmune


Immune Design Corp. (IDC), a privately held biotechnology company developing novel vaccines and immunotherapies for infectious disease and cancer, announced today that it has entered into a license and development agreement with MedImmune for the use and commercialization of IDC’s proprietary Glucopyranosyl Lipid Adjuvant (GLA) as a component in vaccines for select infectious diseases.Immune Design

“We are pleased to enter into this license with MedImmune as one of the world’s leading vaccine research-based pharmaceutical and healthcare companies,” commented IDC Executive Chairman Dr. Bruce Carter.  “This relationship fits very well with IDC’s business model to advance the development of GLA and enable innovative vaccine products that we believe will provide significant benefit in areas of unmet need while maintaining our commitment to global access.”Medimmune

Under the terms of the license agreement, IDC grants MedImmune exclusive worldwide rights to research, develop, use, and commercialize the GLA adjuvant in vaccines for specific indications.  In return, IDC will receive an upfront licensing fee and potential development, regulatory and commercial milestones totaling $212M, in addition to royalty payments on sales of marketed products.

GLA is a toll-like receptor 4 (TLR-4) agonist which IDC has advanced into early clinical stage development.  The small molecule adjuvant has several important features including a pure synthetic composition with straightforward manufacturing and long term stability, a rational design for optimal activation of human dendritic cells, compatibility with antigens in multiple formulations, and a well established safety profile.

Macrogenics-Boehringer Ingelheim pact worth $2.16B


Boehringer Ingelheim and MacroGenics today jointly announced that they have entered into a global alliance to discover, develop and commercialize antibody-based Boehringer Ingelheimtherapeutics which may span multiple therapeutic areas, including immunology, oncology, respiratory, cardiometabolic and infectious diseases.  These developmental drug candidates will be based on MacroGenics’ Dual-Affinity Re-Targeting (DART™) platform and will be directed against up to ten combinations of molecular targets.

“This alliance represents the largest external commitment to our DART platform to date and the latest validation of our ongoing efforts,” said Dr. Scott Koenig, MacroGenics’ President and Chief Executive Officer.  “We are very pleased to be collaborating with the global pharmaceutical research-driven company Boehringer Ingelheim toward the goal of developing next-generation, antibody-based therapeutics.”

“Combining MacroGenics’ innovative DART-based antibody platform with our experience and capabilities in drug discovery and development has the potential to generate breakthrough medicines that will help patients with a range of diseases which cannot be adequately treated at present,” said Prof Wolfgang Rettig, Senior Vice President Corporate Research of Boehringer Ingelheim.

Both companies will share responsibility for discovery and certain preclinical activities.  In addition, Boehringer Ingelheim will have sole responsibility for all subsequent preclinical, clinical, regulatory, commercial and manufacturing activities for any DART-based product resulting from the collaboration.

During the first three years of the collaboration, MacroGenics expects to receive payments of about $60 million, which includes an upfront cash payment, annual maintenance fees, R&D funding, and near-term research-based milestones. Boehringer Ingelheim also expects to make a future equity investment in MacroGenics.  In addition, MacroGenics may be eligible to receive development, regulatory and commercial milestone payments that can reach up to $210 million for each of the ten DART programs in case of full commercial success of multiple DART products.  MacroGenics may also receive tiered royalties on net product sales. MacroGenics has the option to co-promote certain DART products in the United States. Further financial details were not disclosed.

DART Background

The DART platform is a bispecific antibody technology that enables the generation of highly stable antibody-based therapeutic molecules that can simultaneously target two different antigens. DART therapeutics can accommodate virtually any variable region sequence in a “plug-and-play” fashion and have very favorable manufacturing properties. DART proteins are available in both bacterial and mammalian expression systems. DARTs have also been engineered with an Fc domain, which confers them with additional properties, such as Fc receptor binding and extended half-life.

About MacroGenics

MacroGenics is a private, venture-backed biotechnology company that focuses on the discovery, development and delivery to patients of novel biologics for autoimmune disorders, cancer and infectious diseases.  Since its founding in 2000, the company has built a fully-integrated set of capabilities in antibody-based product development.  The company has generated a proprietary pipeline of innovative product candidates by leveraging its three core technology platforms. These proprietary platforms include: (1) cancer stem-like cells; (2) DART technology, which allows the company to incorporate multiple specificities within a single molecule; and (3) Fc optimization, which enhances antibody-dependent effector functions.  The company’s lead program, teplizumab, is an anti-CD3 antibody.  Teplizumab is being investigated in Phase 3 trials for the treatment of autoimmune diseases in collaboration with Eli Lilly and Company.

Body clock "drugs" could ease psychiatric disorders and jet lag


Professor Andrew Loudon from the University of Manchester

Researchers funded by the Biotechnology and Biological Sciences Research Council (BBSRC) and the Medical Research Council (MRC) have successfully used a drug to reset and restart the natural 24 hour body clock of mice in the lab.

The ability to do this in a mammal opens up the possibility of dealing with a range of human difficulties including some psychiatric disorders, jet lag and the health impacts of shift work, like obesity.

Research was led by Professor Andrew Loudon from the University of Manchester and Dr Mick Hastings of the MRC Laboratory of Molecular Biology in Cambridge, working with a multi-disciplinary team of scientists from Pfizer led by Dr Travis Wager, and was published in PNAS.

Professor Loudon said “It can be really devastating to our brains and bodies when something happens to disrupt the natural rhythm of our body clocks. This can be as a result of disease or as a consequence of jet lag or frequent changing between day and night shifts at work.

Professor Janet Allen, BBSRC Director of Research

Most living creatures and plants have an internal body timing system – called the circadian clock. This is a complex system of molecules in every cell that drives the rhythmicity of everything from sleep in mammals to flowering in plants.

Light and the day and night cycle are very important for resetting the clock and the fine adjustments are made through the action of several enzymes, including one called casein kinase 1, which has been the centre of this research

Professor Loudon continued “The circadian clock is linked to the 24 hour day-night cycle and the major part of the clock mechanism ‘ticks’ once per day. If you imagine each ‘tick’ as represented by the rise and fall of a wave over a 24 hour period, as you go up there is an increase in the amount of proteins in the cell that are part of the clock mechanism, and as you go down, these substances are degraded and reduce again. What casein kinase 1 does is to facilitate the degradation part.

“So you can imagine that the faster casein kinase 1 works, the steeper the downward part of the wave and the faster the clock ticks – any change in casein kinase 1 activity, faster or slower, would adjust the ‘ticking’ from 24 hours to some other time period. Consider that if your body suddenly starts working on a 23 hour or 25 hour clock, many of your natural processes, such as sleeping and waking could soon become out of step with day and night.”

Dr Michel Goedert, Head of the Neurobiology Division at Medical Research Council Laboratory of Molecular Biology

The team found a drug that slows casein kinase 1 down and used it in mice where the circadian rhythm has ceased i.e. the clock has stopped ticking all together. In live mice and also in cells and tissue samples from mice, they were able to re-establish the ticking of the clock by using the drug to inhibit the activity of casein kinase 1.

Professor Loudon concluded “We’ve shown that it’s possible to use drugs to synchronise the body clock of a mouse and so it may also be possible to use similar drugs to treat a whole range of health problems associated with disruptions of circadian rhythms. This might include some psychiatric diseases and certain circadian sleep disorders. It could also help people cope with jet lag and the impact of shift work.”

Professor Janet Allen, BBSRC Director of Research said “The most effective way to develop drugs to treat a health problem is to understand the basic biology that underpins what is going on in our bodies. In this case, by understanding the basic biology of the enzyme controlling biological clocks the research team have been able to identify potential drug-based solutions to a range of issues that affect many people’s health and quality of life.”

Dr Michel Goedert, Head of the Neurobiology Division at Medical Research Council Laboratory of Molecular Biology said “We’re all familiar with jet-lag and that sense of being disoriented in time. What is probably less widely understood is how this effect can impact on those with certain mental illnesses. It is crucial to find out what can go wrong at the molecular and cellular level in the brain if we are to determine what treatments will work for patients. If further studies in humans confirm what this study has shown in mice, this could eventually lead to an entirely new approach to treating mental illnesses such as bipolar disorder.”

Dr. Wager, Associate Research Fellow, Pfizer said “It is amazing what can be accomplished when first-rate academic groups and pharmaceutical discovery units team up. Leveraging each other’s talents we now have a deeper understanding of the role casein kinase plays within biological systems. Having the ability to entrain or re-entrain an arrhythmic system opens the door to new treatment option for circadian rhythm disorders. Targeting the inhibition of casein kinase with small molecules may lead to the discovery of novel drugs for the treatment of bipolar depression and other circadian rhythm disorders. The burden of these disorders is enormous and new treatment options are needed.”

Kamada reaches rights agreement with Baxter


Kamada will receive $20 million upfront for the exclusive commercial rights to its emphysema treatment.

Kamada Ltd. today announced a definitive agreement with Baxter International Inc. ,  which will have exclusive commercial rights to Glassia (Alpha 1-Proteinase Inhibitor in the US, Australia, New Zealand and Canada.

Emphysema Image

Glassia, which was approved by the FDA on July 1, 2010, is provides chronic augmentation and maintenance therapy in individuals with emphysema due to congenital deficiency of alpha1-proteinase inhibitor, also known as alpha1-antitrypsin (AAT) deficiency. AAT deficiency is an under-diagnosed hereditary condition that may result in early onset emphysema. Baxter expects to introduce Glassia in the US during the fourth quarter of 2010, and will pursue distribution licenses for Glassia in the other countries for which it has obtained rights.

Baxter BioScience Global BioPharmaceuticals president Larry Guiheen said, “The agreement with Kamada underscores Baxter’s commitment to expanding the diagnosis of alpha1-antitrypsin deficiency by bringing new and innovative therapeutic options to Alpha-1 patients and their treating physicians.”

The distribution agreement includes an upfront cash payment by Baxter of $20 million. The agreement also includes a provision under which Kamada has agreed, for a limited period of time, not to initiate or enter any discussions or agreements relating to the commercialization of Glassia in certain other countries and for Kamada’s investigational next-generation inhaled therapy.

Under a separate license agreement, Baxter has been granted the right to process Glassia and will seek necessary regulatory approvals to enable it to do so. Under this agreement, Baxter may make additional payments of up to $25 million related to milestone achievements and the implementation of technology transfer related to the production of the therapy by Baxter, as well as royalties on product sales.

Roche and Aileron Alliance to Develop Stapled Peptide Drugs for Multiple Therapeutic Areas


$ 1.1 B Agreement  beetwen Roche and Aileron

Aileron Therapeutics and Roche  announced today that they have entered into a collaboration to discover, de

velop and commercialise a new class of drugs called Stapled Peptide Therapeutics. As part of this agreement, Roche will work with Aileron to develop drug candidates against up to five undisclosed targets selected from Roche’s key therapeutic areas,
Stapled Peptide Therapeutics are a result of Aileron’s breakthrough peptide stabilization technology, and are a potential solution to drug as-yet intractable disease targets, including those originating from long sought-after intracellular protein-protein interactions.which include oncology, virology, inflammation, metabolism and CNS.

Under the terms of the agreement, Roche will provide Aileron guaranteed funding of at least $25 million in technology access fees and R&D support. Aileron is eligible to receive up to $1.1 billion in payments upon the achievement of discovery, development, 

Rocheregulatory and commercialisation milestones, if drug candidates are developed against all five targets. In addition, Aileron will receive royalties on future sales for any marketed products that result from the collaboration. Aileron will have substantial responsibility in collaboration with Roche to develop drug candidates against the selected targets up to clinical development.

“Roche is dedicated to advancing innovative therapies, and Stapled Peptides represent a potentially transformative new technology to create drugs for important disease targets that are intractable to currently available modalities,” said Jean-Jacques Garaud, Global Head of Roche Pharma Research and Early Development. “This collaboration with Aileron is a strategically important endeavour for advancing a novel approach to developing new medicines and will accelerate our progress toward our ultimate goal of bringing important new treatments to patients with unmet medical needs.”

“This alliance with Roche validates the broad potential for our Stapled Peptide platform across multiple therapeutic areas and classes of targets and also provides Aileron with capital to advance our platform and internal drug development pipeline,” said Joseph A. Yanchik, III, President and CEO of Aileron. “We took our time to carefully consider several opportunities for our first industry collaboration, and believe that Roche is an ideal partner for Aileron because of its history with peptide therapeutics and its commitment to tackling difficult disease targets.”

About Stapled Peptides

Aileron’s proprietary Stapled Peptide technology platform “locks” peptides into their biologically active shape, mimicking the structures found in nature. This process captures the best features of both small molecules and therapeutic proteins, ultimately endowing the peptide with unique and beneficial drug-like properties, including efficient cell penetration, improved pharmacokinetics, high-affinity binding to large target protein surfaces and excellent stability within the body. This unique combination of features could greatly expand the number of “druggable” therapeutic targets, by providing a unique opportunity to address the thousands of intracellular protein-protein interactions that remain a challenge for functional modulation by current therapeutics. In preclinical studies, Aileron’s Stapled Peptide Therapeutics have been shown to possess remarkable potency, in vivo stability and cell permeability.

About Aileron

Headquartered in Cambridge, Massachusetts, Aileron Therapeutics is a biopharmaceutical company leading the development of a new class of drugs called Stapled Peptide Therapeutics. Stapled Peptides are a breakthrough solution to address thousands of therapeutically important yet currently undruggable targets. Stapled Peptides have demonstrated their unique ability to penetrate cells throughout the body and modulate protein-protein interactions, critical control points for most human diseases. Founded in 2005 and supported by funding from a leading syndicate of investors, Aileron is building a robust pipeline of therapeutics for the treatment of cancer, infectious disease, metabolic disease and immune/inflammatory diseases.

About Roche

Headquartered in Basel, Switzerland, Roche is a leader in research-focused healthcare with combined strengths in pharmaceuticals and diagnostics. Roche is the world’s largest biotech company with truly differentiated medicines in oncology, virology, inflammation, metabolism and CNS. Roche is also the world leader in in-vitro diagnostics, tissue-based cancer diagnostics and a pioneer in diabetes management. Roche’s personalised healthcare strategy aims at providing medicines and diagnostic tools that enable tangible improvements in the health, quality of life and survival of patients. In 2009, Roche had over 80,000 employees worldwide and invested almost 10 billion Swiss francs in R&D. The Group posted sales of 49.1 billion Swiss francs. Genentech, United States, is a wholly owned member of the Roche Group. Roche has a majority stake in Chugai Pharmaceutical, Japan.

Galapagos and University of Bristol enter drug discovery collaboration in chronic pain.Total contract value: €3.3 million


diabetic-neuropathyGalapagos NV (Euronext: GLPG) and the University of Bristol today announced a new drug discovery collaboration aimed at developing treatments for chronic pain associated with diabetes (diabetic neuropathic pain). Galapagos’ service division BioFocus will provide hit-to-lead and lead optimization services for a Wellcome Trust funded program at the University of Bristol. Total contract value for Galapagos could exceed €3.3 million in research fees over two years.

This work is supported by a Seeding Drug Discovery Award from the Wellcome Trust, to a team of researchers led by David Wynick, Professor of Molecular Medicine at the University of Bristol. The project aims to develop a new analgesic drug based on the protein galanin, a small protein that has been shown to reduce neuropathic pain in a number of models of diseases, including diabetes. In earlier studies, several compounds from the BioFocus screening collection were shown to amplify the therapeutic effect of galanin in vitro. In the two-year collaboration announced today, BioFocus will provide medicinal chemistry, biology and ADME/PK for this research project, with the goal to optimize these molecules for the treatment of diabetic neuropathic pain.

“This latest collaboration with the University of Bristol is a prime example of BioFocus’ ability to deliver results and thereby retain partners. Once again we see the BioFocus screening libraries deliver promising hits that are of interest to the academic and pharmaceutical communities,” said Onno van de Stolpe, CEO of Galapagos. “We are pleased that the University of Bristol has expanded and extended this successful relationship into other strong areas of BioFocus expertise.”

“Molecules from the BioFocus collection have shown promise in amplifying the therapeutic properties of galanin in models of neuropathic pain,” said Prof. David Wynick from the University of Bristol. “In this new collaboration with BioFocus, we aim to further optimize these molecules into potential clinical candidates for the treatment of chronic pain associated with diseases such as diabetes.”

Rick Davis, Business Development Manager at the Wellcome Trust, commented “Existing painkillers can prove largely ineffective against neuropathic pain so we are pleased to support this project, which addresses an area of huge unmet clinical need.”

About diabetic neuropathic pain

Diabetes is the most common cause of neuropathic pain, which is often experienced as a burning or electrical pain. Existing painkillers have proven largely ineffective in treating diabetic neuropathic pain, which is believed to be caused by damaged nerves as a result of exposure to toxins or inadequate blood supply. The World Diabetes Foundation predicts that the population of diabetes sufferers will increase from 285 million in 2010 to 438 million by 2030, given the increasing levels of obesity.

About the University of Bristol

The University of Bristol is one of the leading research universities in the UK, having an excellent national and international reputation in research, teaching and global discovery. The University is committed to combining its excellence in research and innovation with a vibrant enterprise culture and is working with government, industry and other partner organisations to encourage the growth of knowledge-based business in South West England. More info at: www.bris.ac.uk [1]

About Galapagos

Galapagos (Euronext: GLPG; OTC: GLPYY) is a mid-size biotechnology company specialized in the discovery and development of small molecule and antibody therapies with novel modes-of-action. The Company is progressing one of the largest pipelines in biotech, with four clinical and over 50 small molecule discovery/pre-clinical programs. Through risk/reward-sharing alliances with GlaxoSmithKline, Eli Lilly, Janssen Pharmaceutica, Merck & Co., Roche and Servier, Galapagos is eligible to receive €3.3 billion in downstream milestones, plus royalties. Together with its BioFocus and Argenta service operations, Galapagos has over 670 employees and operates facilities in six countries, with global headquarters in Mechelen, Belgium. More info at: www.glpg.com

AVI BioPharma Closes New Contract With U.S. Government for Development of Therapeutic Candidates for Ebola and Marburg Hemorrhagic Fever Viruses


AVI BioPharma Discloses New Contract With U.S. Government for Potential Funding of up to $291 Million to Advance Development of Therapeutic Candidates for Ebola and Marburg Hemorrhagic Fever Viruses09-05-who-ebola

AVI BioPharma, a developer of RNA-based therapeutics, yesterday filed a current report on Form 8-K with the U.S. Securities and Exchange Commission providing the following disclosure:

On July 14, 2010, AVI BioPharma, Inc. was awarded a new contract with the U.S. Department of Defense Chemical and Biological Defense Program through the U.S. Army Space and Missile Defense Command for the advanced development of the Company’s hemorrhagic fever virus therapeutic candidates, AVI-6002 and AVI-6003, for Ebola and Marburg viruses, respectively. The contract is funded as part of the Transformational Medical Technologies (TMT) program, which was pioneered to develop innovative platform-based solutions countering biological threats.

The contract is structured into four segments with potential funding of up to approximately $291 million. Activity under the first segment is to begin immediately and provides for funding to the Company of up to approximately $80 million. After completion of the first segment, and each successive segment, TMT has the option to proceed to the next segment for either or both AVI-6002 and AVI-6003. If TMT exercises its options for all four segments, contract activities would include all clinical and licensure activities necessary to obtain FDA regulatory approval of each therapeutic candidate and would provide for a total funding award to the Company of up to approximately $291 million.

The contract was granted in response to proposals the Company submitted to a Request for Proposal (RFP) issued in November 2009 and initially submitted by the Company in February 2010. Under an earlier contract the Company completed development activities that culminated in the opening of Investigational New Drug (IND) applications for both AVI-6002 and AVI-6003.

AVI-6002 and AVI-6003 are RNA-based therapeutic candidates from the Company’s anti-infective portfolio and use AVI’s proprietary PMOplus(TM) chemistry.

About the Transformational Medical Technologies (TMT) Program

The TMT program was created by the DoD to protect the Warfighter from emerging and genetically altered biological threats by discovering and developing a wide range of medical countermeasures through enhanced medical research, development, test and evaluation programs. The TMT Program Office is matrixed from the Joint Science and Technology Office — DTRA and Joint Program Executive Office — Chemical and Biological Defense, with oversight from the Office of the Secretary of Defense. For more information on TMT, visit http://www.tmti-cbdefense.org.

About AVI BioPharma

AVI BioPharma is focused on the discovery and development of novel RNA-based therapeutics for rare and infectious diseases, as well as other select disease targets. Applying pioneering technologies developed and optimized by AVI, we are able to target a broad range of diseases and disorders through distinct RNA-based mechanisms of action. Unlike other RNA-based approaches, our technologies can be used to directly target both messenger RNA (mRNA) and precursor messenger RNA (pre-mRNA) to either down-regulate (inhibit) or up-regulate (promote) the expression of targeted genes or proteins. By leveraging our highly differentiated RNA antisense-based technology platform, we have built a pipeline of potentially transformative therapeutic agents, including a clinical stage Duchenne muscular dystrophy candidate and anti-infective candidates for influenza and hemorrhagic fever viruses.

Watson and Itero Enter Worldwide License Agreement on Biologic Development Candidate For Female Infertility


Recombinant Follicle Stimulating Hormone (rFSH) Would Expand Watson’s Global Presence in Women’s Health
Will Capitalize on Watson’s Eden Biodesign Biologics CapabilitiesWatson Pharmaceuticals, Inc.

Watson Pharmaceuticals, Inc. (NYSE: WPI) today announced an exclusive, worldwide licensing agreement with Itero Biopharmaceuticals, Inc., a venture-backed specialty biopharmaceutical company, to develop and commercialize Itero’s Recombinant Follicle Stimulating Hormone (rFSH).  The product is currently in preclinical development as a biosimilar molecule for the treatment of female infertility.

Under the terms of the agreement, Watson will pay Itero an undisclosed licensing fee and make additional payments based on the achievement of certain development and regulatory performance milestones. Upon successful commercialization, Watson will also pay Itero a percentage of net sales or net profits in various regions of the world.  Watson will assume responsibility for all future development, manufacturing, and commercial expenses related to Itero’s rFSH product.Itero Biopharmaceuticals, Inc.,

“Acquiring the rights to Itero’s rFSH product represents our first in-licensing of a biosimilar development project, and demonstrates the execution of our plan to build a pipeline of biosimilar products, through both internal development and external partnering with high quality biopharmaceutical companies such as Itero,” said Paul Bisaro, Watson’s President and CEO.  “This project will capitalize on the world-class biologics capabilities of our Eden Biodesign group and represents a substantial step in Watson’s goal to build a significant position in the global biopharmaceutical marketplace.”

“Our agreement with Itero also represents continued delivery on our commitment to expand our brand product pipeline with distinctive product opportunities in the growing women’s health market,” said Watson’s Fred Wilkinson, Watson’s Executive Vice President, Global Brands.  “The Eden and Brand research and development teams will manage the development activities, and if we are successful, the Brand commercial organization will add another major product to our portfolio.”

“We are excited to partner with an industry leader in women’s health to complete the development and commercialization of our first biologic asset.  Watson has a strategic focus on growing its women’s health business and this product targets the expanding $1.2 billion infertility segment of this market,” said V. Bryan Lawlis, Ph.D., President and CEO of Itero Biopharmaceuticals. “Itero has created significant value in our rFSH program in just two years, and this collaboration validates our business strategy and capabilities for the cost efficient development of protein therapeutics.  Moreover, it gives Itero the resources to further pursue the development of additional biopharmaceutical products and partnering activities.”

Development of the product will be managed by Watson’s Eden Biodesign biologics unit in collaboration with the Brand research and development team.  Founded in 2000, Eden Biodesign is an integrated biopharmaceutical development and manufacturing organization that provides strategic consultancy, world-class process development, cGMP manufacturing and analytical development services for every significant biopharmaceutical product technology. Eden’s state-of-the-art facility, located in Liverpool, UK, is custom designed for multi-product operation and supports the development of biopharmaceuticals from proof-of-concept through to cGMP manufacture for clinical trials, market launch and commercial supply.

About Itero Biopharmaceuticals, Inc.

Itero Biopharmaceuticals, Inc. is a San Mateo, California-based specialty biopharmaceutical developer focused on clinically and commercially differentiated protein therapeutics. Itero leverages strategic collaborations to provide capital efficient process and manufacturing development as well as global clinical development and commercialization. The company’s management team consists of accomplished executives with extensive development, manufacturing and commercialization experience relating to therapeutic proteins, including monoclonal antibodies.

About Watson Pharmaceuticals, Inc.

Watson Pharmaceuticals, Inc. is a leading global specialty pharmaceutical company. The Company is engaged in the development and distribution of generic pharmaceuticals and specialized branded pharmaceutical products focused on urology and women’s health. Watson has operations in many of the world’s established and growing international markets.

In the U.S., the Watson brand portfolio includes RAPAFLO®, GELNIQUE®, Oxytrol®, TRELSTAR® and INFeD®.  In addition, Watson markets the following brands under co-promotion agreements: AndroGel®, with Solvay Pharmaceuticals, Inc., and Femring®, with Warner Chilcott Limited.  The Watson brand pipeline portfolio includes a number of products, including URACYST®, under development for cystitis; and four novel new contraceptives.  All other trademarks are property of their respective owners.

Aricept long acting formulation benefits patients with advanced Alzheimer


A study found that Alzheimer’s disease patients that used the new long-acting version of Aricept were more likely to maintain or improve brain function than those who continued using  the older formulation.Aricept

Improvement benefited the most to people with more advanced Alzheimer’s. Comparison between the experimental  23-milligram tablet taken once daily with the immediate-release, 10-milligram pill now used,  was favorable to the new formulation,  according to the results released today at the International Conference on Alzheimer’s Disease in Honolulu. No new side effects were seen, the study said.

Tokyo-based Eisai is counting on long-acting and patch versions of Aricept, the world’s best-selling drug for Alzheimer’s, to buffer a potential sales decline when the medicine loses patent protection in the U.S. in November. The company, which generates 60 percent of Aricept’s global sales in the U.S., expects the drug’s revenue in that market to fall about 50 percent in the year ending March 2012, it said in March.

The new formulation is being reviewed by the U.S. Food and Drug Administration, which will make a decision by July 24. It plans to submit data this quarter for regulatory approval to sell the patch version. Eisai aims for the long-acting version of Aricept to reach more than $600 million in peak sales.

The study involved 1,467 people who had moderate to severe Alzheimer’s disease and underwent treatment with the immediate- release Aricept pill for more than three months. Patients then took placebo and either the immediate-release or extended- release pill for six months.

Aricept sales for Eisai rose 6.3 percent to 322.8 billion yen ($3.64 billion) in the year ended March 31, accounting for 40 percent of revenue. The Japanese company pays New York-based Pfizer a fee for co-promotion of Aricept in the U.S. and parts of Europe.

Calithera Biosciences Closes $40 Million in Series A Financing for the treatment of cancer


Calithera Biosciences, a company developing novel oncology therapeutics, today announced the completion of a Series A financing totaling $40 million. The capital will be used to support the company’s pioneering efforts to develop activators of caspases, the proteases that promote apoptotic cell death, for the treatment of cancer and other proliferative diseases.apoptosis

“Promoting apoptosis in cancer cells is a validated approach to the treatment of cancer, as many oncology drugs on the market today are known to kill tumor cells by activating apoptotic pathways, albeit through indirect means,” said Susan Molineaux, Ph.D., co-founder and Chief Executive Officer of Calithera.  “By targeting caspases directly, we hope to develop agents that have broad utility across many types of cancer, with greater specificity than current treatments and the potential to overcome chemoresistance.”

Calithera’s technology was developed by and licensed from the laboratory of co-founder James Wells, Ph.D., chair of the Department of Pharmaceutical Chemistry in the University of California, San Francisco School of Pharmacy.  Dr. Wells’s laboratory has successfully identified several novel compounds that selectively activate procaspases and trigger apoptosis in cancer cells.  Proceeds from the financing will be used to advance one or more caspase activators through preclinical development and into Phase 1 clinical trials in cancer patients.  In parallel, the company will expand its technology for targeting allosteric activating sites to other enzymes with therapeutic potential in cancer.

“Most drug discovery efforts are focused on identifying drugs that inhibit enzyme function,” said Dr. Wells.  “But, interestingly, many cellular enzymes remain dormant until activated.  In the case of caspases, they can be activated on demand by mimicking the natural process with small molecules.”

Expert Leadership Team in Place

The management team of Calithera brings to the company both deep scientific expertise and extensive experience in drug development.

Susan Molineaux, Ph.D., was most recently a founder and Chief Executive Officer of Proteolix, a company that developed proteasome inhibitors.  Proteolix was in late-stage clinical trials with carfilzomib in multiple myeloma when Onyx Pharmaceuticals acquired the company in 2009 for $851 million.  Prior to forming Proteolix, Dr. Molineaux held leadership positions at Rigel Pharmaceuticals and Praecis Pharmaceuticals.  Dr. Molineaux began her career as a scientist in the Immunology group at Merck.

Mark Bennett, Ph.D., Senior Vice President of Research at Calithera, was Vice President of Research at Proteolix.  Previously, he was Director of Cell Biology at Rigel Pharmaceuticals.  Prior to that, Dr. Bennett served as an Assistant Professor in the Department of Molecular and Cell Biology at University of California, Berkeley.

Eric Sjogren, Ph.D., Senior Vice President of Drug Discovery at Calithera, was most recently the Vice President and Head of Medicinal Chemistry at Roche, Palo Alto.  He held a series of positions during his 15-year tenure at Roche.  Prior to that, Dr. Sjogren was at Syntex for eight years.

About Caspases in Cancer

The direct activation and targeting of caspases represents a novel approach to inducing apoptosis in cancer cells and may have utility across a broad range of cancer types while avoiding chemoresistance.  Caspases are the proteases responsible for initiating apoptosis, or programmed cell death, in cancer cells.  Cancer cells grow in an uncontrolled manner in part through their ability to develop mechanisms to resist apoptosis.  Many classic cancer therapies (cytotoxic drugs and radiation therapy) work by inducing upstream pro-apoptotic pathways that then activate caspases to overcome this resistance.

About Calithera Biosciences

Calithera Biosciences was founded in 2010, with core technologies licensed from the University of California, San Francisco, to develop novel therapeutic approaches to the treatment of cancer.  The company is developing small molecules that directly activate caspases, the proteases responsible for initiating programmed cell death, or apoptosis, in cancer cells.  Calithera plans to develop activators of additional enzymes as therapeutic agents for the treatment of cancer and other proliferative diseases.  Located in South San Francisco, CA, Calithera Biosciences is privately held.

Infinity and Intellikine sign $488M pact on Intellikine’s PI3K portfolio in cancer and inflammatory diseases


Infinity Pharmaceuticals, Inc. and Intellikine, Inc., a leader in the development of small molecule drugs targeting the PI3K/mTOR pathway, today announced an agreement under which Infinity obtained global development and commercialization rights to Intellikine’s portfolio of inhibitors of the delta and gamma isoforms of phosphoinositide-3-kinase (PI3K). Among these inhibitors is INK1197, an orally available dual delta/gamma-specific inhibitor of PI3K for which clinical development in inflammatory diseases is expected to commence in 2011.

Under the terms of the agreement, Intellikine will receive $13.5 million in initial license payments, committed research funding over the first two years of the relationship to identify additional novel delta, gamma and dual delta/gamma-specific inhibitors of PI3K for future development, up to $25 million in success-based milestones for the development of two distinct product candidates, and up to $450 million in success-based milestones for the approval and commercialization of two distinct products. In addition, Intellikine will be entitled to receive royalties upInfinity-Pharmaceuticalson successful commercialization of products licensed to Infinity. For products directed primarily to oncology indications, Intellikine will have the option, at the end of Phase 2 clinical development and upon payment of an option fee, to convert its royalty interest in U.S. sales into the right to share in 50% of profits and losses on U.S. development and commercialization, and to participate in up to 30% of the detailing effort for these products in the United States.

The PI3Kdelta/gamma program licensed from Intellikine will be a part of Infinity’s existing strategic alliance with Mundipharma International Corporation Ltd. and will be governed by the same terms as Infinity’s internally-discovered programs. Such terms include Mundipharma’s funding of Infinity’s research and development expenses for the PI3K program through the later to occur of December 31, 2013 and the commencement of Phase 3 development, subject to aggregate funding caps across the partnered portfolio under a three-year rolling plan, and reimbursement of 50% of research and development expenses thereafter. In addition, Mundipharma will have commercialization rights outside of the United States to any successfully developed products, subject to the payment of royalties of up to 20% on net sales.

“This agreement is emblematic of Infinity’s strategy to use our scientific expertise and financial strength to expand our portfolio of high-quality development programs in areas where there is a significant unmet medical need and for which Infinity is well positioned to reveal — and then realize — the potential of such programs. We expect to seek additional opportunities to broaden our portfolio of innovative product candidates in the future,” said Adelene Q. Perkins, president and chief executive officer of Infinity. “We are excited to develop INK1197 in inflammation and to work closely with the Intellikine team to identify additional differentiated PI3Kdelta/gamma inhibitors for both inflammation and oncology,” said Julian Adams, Ph.D., president of research and development at Infinity. “Targets such as PI3Kdelta and PI3Kgamma have broad applicability across inflammatory and oncology indications, creating many opportunities to make a meaningful impact for patients.”

Intellikine has rapidly assembled a leading pipeline of drug candidates against the PI3K/mTOR pathway,” said Troy Wilson, Ph.D., J.D., president and chief executive officer of Intellikine. “We are excited to work with our colleagues at Infinity, who share our strong scientific culture and sense of urgency to advance this program forward. Additionally, this collaboration provides us with significant resources to advance our own TORC1/2 and PI3Kalpha drug candidates. The opportunity to co-develop and co-detail PI3Kdelta/gamma drug candidates in oncology with Infinity is a key component of our strategy to build an oncology business.”

By virtue of the expansion of Infinity’s portfolio to include the PI3Kdelta/gamma program, Infinity expects to exceed the $65 million cap for 2010 set forth in the research plan under the Mundipharma/Purdue Pharma alliance. As a result, Infinity now projects a 2010 cash burn of between $35 and $45 million and a year-end cash balance of between $85 and $95 million, not including amounts that may be drawn by Infinity under the $50 million line of credit available from Purdue. Infinity continues to expect that its current cash and investments, together with research and development funding from Mundipharma and Purdue and proceeds from the line of credit, are sufficient to fund the company’s operations into 2013 and enable the company to reach key development milestones and evaluate additional external opportunities to strategically enhance its pipeline.

About PI3K and INK1197

The phosphoinositide-3-kinases (PI3Ks) are a family of enzymes involved in cellular functions, including cell proliferation and survival, cell differentiation, intracellular trafficking and immunity. The delta and gamma isoforms of PI3K are strongly implicated in immune-mediated inflammatory and allergic disorders. Restricted primarily to cells of the immune system, these two isoforms regulate diverse cellular functions of the immune system. INK1197 is an orally-available, small molecule, dual-selective inhibitor of PI3Kdelta and PI3Kgamma. INK1197 has demonstrated activity in preclinical models of rheumatoid arthritis, allergy and inflammation. Infinity intends to develop INK1197 in immune-mediated inflammatory diseases. Beyond INK1197, Intellikine will contribute its collection of novel PI3Kdelta-selective and PI3Kdelta/gamma dual-selective compounds, providing multiple opportunities for Infinity to develop differentiated therapies against inflammatory and autoimmune diseases as well as hematologic cancers.

About Infinity Pharmaceuticals, Inc.

Infinity is an innovative drug discovery and development company seeking to discover, develop, and deliver to patients best-in-class medicines for difficult-to-treat diseases. Infinity combines proven scientific expertise with a passion for developing novel small molecule drugs that target emerging disease pathways. Infinity’s programs in the inhibition of the Hsp90 chaperone system, the Hedgehog pathway and fatty acid amide hydrolase are evidence of its innovative approach to drug discovery and development.

About Intellikine, Inc.

Intellikine is a private, clinical-stage company focused on the discovery and development of innovative small molecule drugs targeting the PI3K/mTOR pathway. Intellikine’s most advanced program, INK128, a selective TORC1/2 inhibitor for the treatment of cancer, is currently in a Phase 1 clinical trial in patients with advanced solid tumors. In addition, Intellikine was recently awarded a $1 million grant from the Multiple Myeloma Research Foundation to advance INK128 as a potential treatment for patients with multiple myeloma. Intellikine is also advancing a first-in-class PI3Kalpha-selective inhibitor, INK1117, which is currently being prepared for human clinical trials in cancer. Beyond INK128 and INK1117, Intellikine has generated one of the leading pipelines of drug candidates against important therapeutic targets in this pathway.

Merck announced plans to phase out operations at eight research sites and eight manufacturing sites


Richard T. Clark, chairman and chief executive officer of Merck

Merck & Co., Inc. (NYSE: MRK), known outside the U.S. and Canada as MSD, today provided further detail on integration plans for the company’s research and development, manufacturing and other business operations as part of a global restructuring program announced following the November 2009 merger of Merck and Schering-Plough. The consolidation plans support Merck’s strategic direction  to invest in key areas for future growth, including emerging markets, biologics, vaccines and consumer care.

Merck today announced plans to phase out operations at eight research sites and eight manufacturing sites, as well as to continue to consolidate office facilities worldwide, as part of the global merger restructuring program that began last December. The goal of the restructuring is to create a flexible R&D organization that cultivates scientific innovation, facilitates external collaboration and drives pipeline progress and a reliable, more fully utilized and cost efficient worldwide manufacturing supply chain to support Merck’s broader product portfolio.

Merck continues to expect its total workforce to be reduced by approximately 15 percent across all areas of the combined company worldwide as part of the initial phases of its merger restructuring program. The company said it will continue to hire new employees in strategic growth areas of the business as necessary.

“Today’s announcement is another important step as we successfully integrate our global operations on schedule and move forward with Merck’s strategic priorities,” said Richard T. Clark, chairman and chief executive officer of Merck. “These changes are crucial to drive future growth and realize the promise of being a global health care leader for the long term. While we believe these actions are necessary to support Merck’s competitive advantage, they required difficult decisions that will impact some of our colleagues, their families and local communities. We will implement our restructuring plans with the utmost care and respect for the hard-working and talented employees of Merck,” he said.

Merck said it remains committed to achieving its previously announced synergy target of $3.5 billion in ongoing annual savings in 2012. With the plans announced today, Merck expects the initial phases of the merger restructuring program to result in savings of approximately $2.7 to $3.1 billion in 2012 toward the $3.5 billion target. The company said synergy target savings will also come from non-restructuring-related activities, such as its ongoing procurement savings initiative. The company estimates that cumulative pretax costs for the initial phases of the merger restructuring program will now range from $3.5 billion to $4.3 billion. Merck expects that a charge for certain portions of these costs will be recorded in the second quarter of 2010. Merck said that approximately two-thirds of the cumulative pretax costs will relate to cash outlays, primarily due to employee separation expense. About one-third of the cumulative pretax costs are expected to be non-cash, relating primarily to the accelerated depreciation of facilities to be closed or divested.

Merck is taking a careful and thoughtful approach to these actions, including exploring appropriate local partnerships, business development initiatives and, in some cases, site sales to help minimize the potential impact on communities and employees. The company said its evaluation of these opportunities as well as the company’s global network continues. Merck will comply with all local laws and regulations, including where applicable, any requirements to inform or consult with works councils, trade unions or other employee representative bodies.

Merck Research Laboratories

The Merck Research Laboratories network is being restructured to ensure efficient and successful delivery of Merck’s pipeline of promising candidates. The new network will be comprised of 16 major research and development facilities worldwide. Merck will retain clinical development and regulatory affairs expertise in major regions around the world including the U.S., Europe, Asia and Japan.

At the core of Merck’s research network are several large multidisciplinary sites that will support multiple research franchises. These sites provide the capabilities and resources to advance research priorities and respond quickly to change. The new network structure positions Merck to deliver important products that span biologics, small molecules and vaccines.

As part of today’s announcement, Merck plans to phase out operations at eight research sites over the next two years. These sites include: Montreal, Canada; Boxmeer (Nobilon facility only), Oss, and Schaijk, Netherlands; Odense, Denmark; Waltrop, Germany; Newhouse, Scotland; and Cambridge (Kendall Square), Massachusetts, U.S.

The company’s research division will retain its focus on seven key therapeutic franchise areas: Cardiovascular Disease; Diabetes and Obesity; Infectious Disease; Oncology; Neuroscience and Ophthalmology; Respiratory and Immunology; and Women’s Health and Endocrine. Merck’s women’s health research, currently centered in Oss, the Netherlands, will be relocated primarily to the U.S. The company remains committed to discovering and developing treatments and products for women’s health and will pursue global research collaborations. The continued focus on core franchise areas is aligned with the company’s global scientific strategy of retaining deep internal therapeutic area and functional expertise in core areas while strategically collaborating with partners to access external innovation.

Merck Manufacturing Division

Merck is realigning its global manufacturing network to create a focused, more fully-utilized and cost-efficient worldwide supply chain in support of the company’s broader product portfolio. The company’s core manufacturing activity will be focused on areas where it has unique expertise and capabilities, while leveraging a virtual global network of suppliers. Plans announced today as well as other actions taken since the merger would reduce Merck’s manufacturing network from 91 facilities at the close of the merger to 77 facilities. This includes 29 animal health facilities that are the subject of the planned joint venture of Intervet Schering-Plough with sanofi-aventis’s Merial, which are not included in this restructuring program. The company will continue to pursue productivity efficiencies and evaluate its manufacturing supply chain capabilities on an ongoing basis.

Beginning in the second half of 2010, the company will phase out operations at eight manufacturing facilities and these sites will exit the global network as activities are transferred to other locations. Specifically, the company intends to cease manufacturing activities at its facilities in Comazzo, Italy; Cacem, Portugal; Azcapotzalco, Mexico; Coyoacan, Mexico, and Santo Amaro, Brazil, and intends to sell the Mirador, Argentina and Miami Lakes, Florida, facilities. In Singapore, chemical manufacturing will be phased out at the legacy Merck site, but it will continue at the legacy Schering-Plough site. The company’s extensive pharmaceutical manufacturing operations will continue at these two Singapore facilities.

Merck will continue to make new strategic investments to support its worldwide product supply needs, particularly in emerging markets. In Latin America, for example, new investments are being made by Merck at its Xochimilco, Mexico and Campinas, Brazil facilities to increase capacity.

Sanofi creates 300 new jobs and invests $65M in Boston HQ expansion


One of the world’s largest drug makers, Sanofi-Aventis SA, is planning a $65 million expansion in Cambridge that will create about 300 jobs, making it the latest foreign pharmaceutical giant to invest in Massachusetts.

The Paris-based drug maker is in the process of leasing space in Cambridgeport, where it will establish a joint headquarters for a new cancer division.

We believe that Cambridge is really the heart of oncology today,’’ Hanspeter Spek, president of Sanofi-Aventis’s global operations, told financial analysts and investors in a conference call earlier this year. “We intend to benefit from this environment as a neighbor.’’

Sanofi-Aventis is the latest foreign drug maker expanding its operations in Massachusetts. Industry executives say the companies are drawn to the intense concentration of medical and life sciences activities in the area, including top-flight research universities, respected hospitals, and a cluster of biotechnology companies.

The company’s investment is particularly important because it comes at a time when many other businesses are reluctant to expand because of the weak economy. And pharmaceutical research, manufacturing, and management jobs tend to pay well and pump new money into the economy, benefiting ancillary businesses such as suppliers, law firms, and nearby hotels and restaurants. Sanofi-Aventis predicted the new jobs would pay an average of more than $100,000 per year.

Governor Deval Patrick has also been counting on growth in the industry to help lift the state’s economy. Two years ago, Patrick launched a $1 billion, 10-year initiative that includes tax incentives for life sciences companies to expand, research grants for scientists, and money to build university labs and other public infrastructure to support the industry.

Just last week, 56 life sciences companies, including Sanofi-Aventis, applied for $25 million in tax credits. The tax credits will be awarded in December. Last year, 26 firms received $24.5 million.

More than a half dozen other major European and Asian pharmaceutical companies have major operations in the Boston area, including Swiss drug maker Novartis AG, Merck KGaA of Germany, Japanese drug makers Takeda Pharmaceutical Co. and Dainippon Sumitomo Pharma Co., and British pharma giants GlaxoSmithKline PLC, AstraZeneca PLC, and Shire PLC.

And despite the downturn, several life science firms are adding employees in Massachusetts, either through internal expansion or by acquisitions of other companies.

Two years ago, Shire launched a $394 million expansion in Lexington, including building a new manufacturing plant and headquarters for its Human Genetic Therapies unit, which develops drugs to treat rare medical disorders, such as Fabry disease. The company, which received $48 million in incentives to expand in Massachusetts instead of in another state vying for the project, has 1,300 employees and expects to add as many as 300 more by 2015. Shire recently inked a $165 million deal to buy several of the buildings it was leasing in Lexington.

Merck is completing a $65 million research-and-development center in Billerica for its EMD Serono unit and recently agreed to buy Millipore Corp., a Billerica company that provides equipment and services to the life sciences industry, for $6 billion. Dainippon Sumitomo Pharma Co. acquired Sepracor Inc,. the Marlborough company behind the Lunesta sleep medicine, for $2.6 billion in April.

We are continuing to see investment growth here even in places where they might be shrinking in other parts of the world,’’ said Susan Windham-Bannister, the Life Sciences Center’s president.

Overall, the Massachusetts biotechnology and pharmaceutical industry had more than 45,900 workers in 2008, the latest estimate available, up 43 percent from 2001, according to the biotechnology council.

Sanofi-Aventis has nearly 400 workers in Massachusetts, including 160 in Cambridge, largely through its 2008 acquisition of Acambis, a vaccine maker based in England. It also owns a small manufacturing facility in Canton.

The new cancer operation in Cambridgeport will boost those numbers considerably. Sanofi-Aventis has posted dozens of jobs related to the new division headquarters on its website, including for laboratory research, clinical trials, and marketing. It has sublet 30,000 square feet of space elsewhere in Cambridge, but is now close to leasing 112,000 square feet at 640 Memorial Drive, an MIT-owned building aimed at life sciences companies, for the new division headquarters. The Cambridge location will share control of the cancer division with a Sanofi-Aventis office in Vitry, France.

Company spokesman Jack Cox said the firm hopes to finalize a lease in the next few weeks.

To help support the expansion, Sanofi-Aventis also applied this month for $2.45 million in state tax credits from the Life Sciences Center and plans to request another $6.5 million in aid over the next four years, according to the center.

Like other major pharmaceutical companies, Sanofi-Aventis is making a big bet on cancer drugs. Last month it announced plans to buy San Diego biotechnology firm TargeGen Inc., which is developing a treatment for certain types of leukemia, lymphoma, and other blood disorders, for $75 million, plus up to $485 million in additional incentives. Last year it agreed to pay up to $500 million for BiPar Sciences, which is developing a new class of “tumor-selective drugs’’ to treat multiple types of cancer. BiPar is based outside San Francisco.

Sanofi-Aventis, which also has major operations in Pennsylvania, New Jersey, and elsewhere in the United States, already has two blockbuster cancer drugs. Taxotere, a chemotherapy drug used to treat breast cancer, prostate cancer, and other types of cancers, generated $2.8 billion in sales last year. Eloxatin, used to treat colorectal cancer, reaped more than $1.2 billion for Sanofi-Aventis last year.

Last month, the US Food and Drug Administration approved Sanofi-Aventis’s Jevtana to be used in combination with another drug to treat metastatic hormone-refractory prostate cancer, and the company has an array of additional cancer drugs in its pipeline.

It has also been working with Massachusetts biotechnology firms to develop new drugs, including deals related to cancer research with Dyax Corp. in Cambridge, ImmunoGen Inc. in Waltham, and Merrimack Pharmaceuticals Inc. in Cambridge.

Debasish Roychowdhury, who runs Sanofi-Aventis’s new oncology unit, praised Cambridge yesterday in a statement as a natural choice for the joint headquarters “given the city’s role as one of the world’s most important centers for biotech research and talented oncology minds.’’

University of Maryland School of Medicine Scientists Develop New Strategy That May Improve Cognition


University of Maryland, Davidge Hall

For the first time, scientists have linked a brain compound called kynurenic acid to cognition, possibly opening doors for new ways to enhance memory function and treat catastrophic brain diseases, according to a new study from the University of Maryland School of Medicine. When researchers decreased the levels of kynurenic acid in the brains of mice, their cognition was shown to improve markedly, according to the study, which was published in the July issue of the journal Neuropsychopharmacology. The study is the result of decades of pioneering research in the lab of Robert Schwarcz, Ph.D., a professor of psychiatry, pediatrics and pharmacology and experimental therapeutics at the University of Maryland School of Medicine.
We believe that interventions aimed specifically at reducing the level of kynurenic acid in the brain are a promising strategy for cognitive improvement in both healthy individuals and in those suffering from a variety of brain diseases ranging from schizophrenia to Alzheimer’s disease,” says Dr. Schwarcz.
Kynurenic acid is a substance with unique biological properties and is produced when the brain metabolizes the amino acid L-tryptophan. The compound is related to another breakdown product of tryptophan known as quinolinic acid. In 1983, Dr. Schwarcz published a paper in the journal Science identifying the critical role excessive quinolinic acid plays in the neurodegenerative disorder Huntington’s disease. He has since designed a therapeutic strategy targeting quinolinic acid for the treatment of Huntington’s disease. Dr. Schwarcz also is involved in a company called VistaGen, which pursues the development of neuroprotective drugs based on this concept.
In the study published this month, Dr. Schwarcz and his colleagues at the Maryland Psychiatric Research Center – a world-renowned clinical and basic science research center at the University of Maryland School of Medicine – examined mice that had been genetically engineered to have more than 70 percent lower kynurenic acid levels than ordinary mice. These mice were found to perform significantly better than their normal peers on several widely used tests that specifically measure function in the hippocampus. The hippocampus is a critical area of the brain for memory and spatial navigation. The mice were clearly superior in their ability to explore and recognize objects, to remember unpleasant experiences and to navigate a maze. The engineered animals also showed increased hippocampal plasticity, meaning they had a greatly improved ability to convert electrical stimuli into long-lasting memories.
These results are very exciting, because they open up an entirely new way of thinking about the formation and retrieval of memories,” says Dr. Schwarcz. “Kynurenic acid has been known for more than 150 years, but only now do we recognize it as a major player in one of the fundamental functions of the brain. Our most recent work, still unpublished, shows that new chemicals that specifically influence the production of kynurenic acid in the brain predictably affect cognition. We are now in the process of developing such compounds for cognitive enhancement in humans.”
I feel confident Dr. Schwarcz’s determined pursuit of answers for the desperate patients suffering from devastating neurodegenerative disorders such as Alzheimer’s disease and Huntington’s disease, and psychotic disorders such as schizophrenia, will pay off,” says E. Albert Reece, M.D., Ph.D., M.B.A., vice president for medical affairs, University of Maryland, and John Z. and Akiko K. Bowers Distinguished Professor and dean, University of Maryland School of Medicine. “His work creates hope for these patients and their families, and his findings are making a significant impact on the field of neuroscience and psychiatric medicine

Compugen Discovered Protein Shown to Abolish Recurring Relapses in Multiple Sclerosis Animal Model


  • Compugen Discovered Protein Shown to Abolish Recurring Relapses in Multiple Sclerosis Animal Model
  • CGEN-15001 also demonstrates pronounced delay of disease onset and significant decrease in disease symptoms

Existence of B7/CD28 family member initially predicted by Compugen’s LEADS Platform and proprietary algorithm for predicting novel protein family members

Compugen Ltd. (CGEN 3.38, -0.05, -1.46%) announced today that administration of CGEN-15001 in an animal model of multiple sclerosis (MS) has been shown to completely abolish spontaneous relapses. In addition, administration of this novel molecule prior to disease onset demonstrated a pronounced delay of disease onset and a significant decrease in disease symptoms. These results, together with complementary results from earlier studies, strongly support a significant potential therapeutic utility for CGEN-15001 in the treatment of multiple sclerosis and other autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, and type 1 diabetes.

CGEN-15001 is a soluble recombinant fusion protein comprised of the extracellular region of a Compugen discovered B7/CD28 family member, designated CGEN-15001T. CGEN-15001T, which itself has potential medical utilities – such as serving as a target for antibody therapeutics – was discovered by Compugen through the use of its LEADS platform and a proprietary algorithm designed to predict novel members of known protein families. Patents have been filed for both CGEN-15001 and CGEN-15001T.

The recently completed study of CGEN-15001 utilized the relapsing-remitting autoimmune encephalomyelitis mouse model. This well-recognized animal model of multiple sclerosis manifests an autoimmune CNS demyelinating disease with clinical and pathologic similarity to human relapsing-remitting multiple sclerosis. Relapsing-remitting multiple sclerosis is the most common form of MS affecting approximately 85% of the 2.5 million people worldwide diagnosed with MS. Relapses in multiple sclerosis patients result in recurring attacks of clinical symptoms which lead to a worsening of existing symptoms or to the appearance of new symptoms. Thus, prevention of relapses is a major goal in the development of treatments for multiple sclerosis, and the demonstrated therapeutic effect of CGEN-15001 in the presence of this established disease, as demonstrated in this animal model, is highly relevant for its potential use in human therapy.

Professor Stephen Miller from Northwestern University, a leading scientist in this field who supervised the studies, stated, “The capacity of CGEN-15001 to prevent the development of disease in this well-recognized animal model for multiple sclerosis, and more significantly to ameliorate its progression when administered in the presence of pre-existing disease is quite dramatic. Furthermore, these beneficial effects were shown to be long lasting and persisted through the study, indicating that CGEN-15001 may prevent disease progression as efficiently as immune tolerance induction, a process whereby the immune system no longer attacks the self antigens that cause the disease. These findings, together with those demonstrated in our earlier studies, are unique among the molecules targeting the B7 family of co-stimulatory molecules that have been published to date.”

Compugen’s VP R&D, Dr. Zurit Levine stated, “In addition to being an extremely exciting discovery, this is a good example of how our extensive infrastructure of predictive capabilities can be utilized for ‘discovery on demand’ purposes. In this case, we were interested in finding a new member of the B7 protein family, a family of proteins that are widely believed to have substantial therapeutic potential. However, it was our belief that relying only on commonly used discovery approaches, such as sequence and functional homology, which underlie most such efforts by others, would be unlikely to yield all unknown members for this family.”

Dr. Levine continued, “We utilized, therefore, a different predictive discovery approach combining certain components of our LEADS infrastructure platform with a proprietary algorithm that had been developed to predict in silico novel members of a known protein family based on genomic information, protein structure and additional characteristics. This led to the prediction and selection of a number of novel proteins, including CGEN-15001T, and the discovery of CGEN-15001T led to the identification of the CGEN- 15001 protein.”

About the B7/CD28 protein family

Members of the B7/CD28 family have been intensively studied over the past decade and have brought much excitement to the field of immune regulation. The activation and development of an adaptive immune response is initiated by the engagement of a T-cell antigen receptor with an antigenic peptide-MHC complex. The outcome of this engagement is determined by both positive and negative co-stimulatory signals, generated mainly by the interaction between the B7 family and their receptor CD28 family. A growing body of evidence indicates that the dysfunction of immune regulation contributes to the development of autoimmune diseases.

Positive and negative co-stimulatory pathways play critical roles in immune regulation and are considered potential targets for modulating chronic inflammation in autoimmune diseases. To date, one soluble recombinant fusion protein, that selectively blocks the co-stimulatory signal mediated by the B7/CD28 pathway, has been cleared for marketing in the U.S. for the treatment of moderate to severe rheumatoid arthritis, and is in clinical trials for other autoimmune indications. In addition, a number of clinical and preclinical studies of this protein family are underway at various companies.

About LEADS

The LEADS platform provides a comprehensive predictive view of the human transcriptome, proteome and peptidome, and serves as a rich infrastructure for the discovery of novel genes, transcripts and proteins. It includes extensive gene information and annotation, such as splice variants, antisense genes, SNPs, novel genes and RNA editing. At the protein level, LEADS provides full protein annotation, including homologies, domain information, subcellular localization, peptide prediction and novelty status.

About Compugen

Compugen is a leading drug and diagnostic product candidate discovery company. Unlike traditional high throughput trial and error experimental based discovery, Compugen’s discovery efforts are based on in silico (by computer) prediction and selection utilizing a growing number of field focused proprietary discovery platforms accurately modeling biological processes at the molecular level. Compugen’s growing number of collaborations with major pharmaceutical and diagnostic companies cover both (i) the licensing of product candidates discovered by Compugen during the validation of its discovery platforms and in its internal research, and (ii) “discovery on demand” agreements where existing or new Compugen discovery platforms are utilized to predict and select product candidates as required by our partner. In 2002, Compugen established an affiliate, Evogene Ltd. (www.evogene.com) (TASE:EVGN.TA), to utilize certain of the Company’s in silico predictive discovery capabilities in agricultural biotechnology

Kamada wins FDA approval for Glassia – a new liquid, ready- to-use treatment for Alpha-1 Antitrypsin Deficiency


Alpha 1-antitrypsine deficiency lung CT scan.JPEG Computed tomography of the lung with thin slices (1 mm) showing emphysema and bullae in the lower lung lobes of a subject with type ZZ alpha-1-antitrypsin deficiency. There is also increased lung density in areas with compression of lung tissue by the bullae. Source: Wikipedia

Kamada (TASE:KMDA), today announced that the United States Food and Drug Administration (FDA) has approved Glassia™ (Alpha 1 Proteinase inhibitor, also known as Alpha-1-Antitrypsin (AAT) for the treatment of Alpha 1 deficiency (AATD). Glassia™ is now the first and only liquid Alpha- 1-Proteinase Inhibitor worldwide available liquid, ready to use, Alpha- 1-Proteinase Inhibitor on the market.

The FDA approved GlassiaTM following review of Kamada’s Biological License Application (BLA) submitted in May 2009. The FDA’s review included Kamada’s clinical development as well as auditing and approving Kamada’s manufacturing facility, quality assurance and controls.

David Tsur, Chief Executive Officer of Kamada said, “We are very proud with this achievement. This success belongs to each one of the company’s employees. With this unique product, Kamada is able to offer the US Alpha-1 patients a new liquid, ready- to- use drug that may ease their therapy routine and provide an additional high quality product in the US market for the benefit of this community.
We are committed to the Alpha-1 patient community and take great pride in further developments of our second generation product, an inhaled Alpha- 1-Proteinase Inhibitor currently in stage 2-3 clinical development “.

John Walsh, President of the US Alpha-1 Foundation congratulated Kamada, “we are delighted to welcome Kamada to the US market. Glassia™ offers a new and an innovative therapeutic alternative for our patients and we look forward to the company’s entry into our patient community”.

About Glassia
Glassia™ is a unique, high purity, liquid, ready-to-use liquid Alpha- 1-Proteinase Inhibitor that is indicated for chronic augmentation and maintenance therapy in adults with emphysema due to congenital deficiency of alpha1-proteinase inhibitor, also known as Alpha1-Antitrypsin Deficiency. The product is produced using a patented proprietary chromatographic purification method.

About Kamada
Kamada is a public biopharmaceutical company (TASE: KMDA) developing, producing and marketing a line of specialty life-saving biopharmaceuticals. Licensed and marketed worldwide, several of these specialty therapeutics are currently undergoing advanced clinical trials.
Kamada is currently in the process of conducting a clinical trial with its second generation AAT product- an inhaled formula which is currently in a phase 2-3 for the indication of Alpha1-Antitrypsin Deficiency.

Celgene and Abraxis BioScience deal worth $2.9B


ABRAXANE® Approved for Second-Line Use in Metastatic Breast Cancer, Establishes Celgene in Solid Tumors Complementing Its Leadership Position in Blood Cancers Abraxane

Recent Clinical Data Presented at ASCO and AACR for ABRAXANE in First-Line Non-small Cell Lung Cancer and First-Line Pancreatic Cancer Highlights Significant Growth Opportunities

Celgene Reaffirms 2010 Non-GAAP Financial Outlook; Expects Acquisition to be Modestly Dilutive to Non-GAAP Earnings in 2011 and Accretive in 2012 and Beyond; Acquisition Expects to Add Approximately $1 Billion in Revenue in 2015

Celgene Corporation (NASDAQ: CELG) and Abraxis BioScience Inc. (Nasdaq: ABII) jointly announced the signing of a definitive merger agreement in which Celgene has agreed to acquire Abraxis BioScience. Under the terms of the merger agreement, each share of Abraxis BioScience common stock will be converted into the right to receive an upfront payment of $58.00 in cash and 0.2617 shares of Celgene common stock. The upfront payment values Abraxis BioScience at approximately $2.9 billion, net of cash. Each share will also receive one tradeable Contingent Value Right (CVR), which entitles its holder to receive payments for future regulatory milestones and commercial royalties. The transaction is expected to be modestly dilutive to non-GAAP earnings in 2011 and accretive in 2012 and beyond.

The acquisition of Abraxis BioScience accelerates Celgene’s strategy to become a global leader in oncology. The transaction adds ABRAXANE for Injectable Suspension (paclitaxel protein-bound particles for injectable suspension) (albumin-bound) to the Company’s existing portfolio of leading cancer products.  ABRAXANE was approved in January 2005 by the U.S. Food and Drug Administration (FDA) for the treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within six months of adjuvant chemotherapy.  Prior therapy should have included an anthracycline unless clinically contraindicated. ABRAXANE was approved by the European Medicines Agency in January 2008 for a similar indication. Additionally, ABRAXANE® has received orphan drug designation for stage IIB-IV melanoma and pancreatic cancer.

“The acquisition of Abraxis BioScience is an exceptional strategic fit that will accelerate our strategy of becoming a global leader in oncology,” said Bob Hugin, Chief Executive Officer of Celgene Corporation. “We are excited by the opportunity to leverage our clinical, regulatory and commercial capabilities to provide metastatic breast cancer patients with an innovative treatment in ABRAXANE. We are also excited by the potential of ABRAXANE to treat additional solid tumor malignancies such as non-small cell lung and pancreatic cancer.  Finally, the potential of nab®-based therapeutics developed by Abraxis coupled with Celgene’s innovative science offers the potential to deliver long-term value to patients, doctors and all of our stakeholders.”

“Our nab technology platform is changing the treatment paradigm for difficult-to-treat cancers,” said Patrick Soon-Shiong, M.D., Executive Chairman of Abraxis BioScience. “In Celgene we have found the ideal partner to further expand the reach of ABRAXANE and our other treatments, in order to improve the lives of patients worldwide.”

About nab®-Driven Chemotherapy
Abraxis BioScience has developed a proprietary nanoparticle albumin bound (nab) technology which leverages albumin nanoparticles for the active and targeted delivery of chemotherapeutics to the tumor. This nab-driven chemotherapy provides a new paradigm for penetrating the blood-stroma barrier to reach the tumor cell. The proposed mechanism of delivery of this nab-driven chemotherapy is thought to be by targeting a previously unrecognized tumor-activated, albumin-specific biologic pathway with a nanoshell of the human blood protein albumin. This nano-shuttle system is believed to activate an albumin-specific (Gp60) receptor-mediated transcytosis path through the cell wall of proliferating tumor cells, using caveolin-1 activated caveolar transport. Once in the stromal micro-environment, the albumin-bound drug may be preferentially localized by a second albumin-specific binding protein, SPARC, a protein secreted into the stroma by tumor cells. The resulting collapse of stroma surrounding the tumor cell may thus enhance the delivery of the nab-chemotherapeutic to the intracellular core of the tumor cell itself.

Recent ABRAXANE Clinical Data: First-line Non-small Cell Lung Cancer
At the 46th Annual Meeting of the American Society of Clinical Oncology (ASCO) held earlier this month in Chicago, 34 scientific abstracts evaluating the use of ABRAXANE were presented.  Data presented from a randomized phase III trial evaluating ABRAXANE plus carboplatin showed a statistically significant (p=0.005) 31 percent improvement in overall response rate (ORR) when compared with paclitaxel plus carboplatin in the first-line treatment of patients with non-small cell lung cancer (NSCLC). These data achieved the primary end point agreed to with the FDA in a Special Protocol Assessment. In addition, a retrospective analysis of the highly difficult-to-treat subset of squamous cell carcinoma, showed a 67 percent improvement in ORR (p<0.001) in those who received the ABRAXANE combination versus those who received the paclitaxel combination.

Recent ABRAXANE Clinical Data: Advanced Pancreatic Cancer
Data was also presented at the recent ASCO meeting from a phase II clinical study evaluating ABRAXANE in advanced pancreatic cancer patients who have progressed on gemcitabine-based therapy. Treatment resulted in 58 percent of patients achieving six-month overall survival (OS), with a median survival of 7.3 months and a median progression-free survival (PFS) of 1.6 months. Five patients remain alive at a median follow-up of 12.7 months, including one patient with stable disease (SD) on cycle 15 of therapy. These results follow data presented at the 101st Annual Meeting of the American Association for Cancer Research (AACR) in April 2010 from a phase 1/2 study of ABRAXANE in combination with gemcitabine, which demonstrated increased survival in first-line treatment of patients with advanced pancreatic cancer. Median OS for 44 patients treated at the recommended dose of 125 mg/m2 nab-paclitaxel (ABRAXANE) plus gemcitabine (1000 mg/m2) was 12.2 months, a doubling of survival compared to historical control of gemcitabine alone. Enrollment is ongoing for a phase III trial program evaluating nab-paclitaxel plus gemcitabine versus gemcitabine alone as a first-line therapy for advanced metastatic pancreatic cancer.

Eli Lilly buys Alnara Pharma; Enzymatic treatment for cystic fibrosis, a life threatening genetic disorder.


alnaraEli Lilly and Company (NYSE: LLY) and Alnara Pharmaceuticals, Inc. today announced they have signed a definitive merger agreement whereby Lilly will acquire Alnara, a privately held biotechnology company developing protein therapeutics for the treatment of metabolic diseases.

Alnara’s lead product in development is liprotamase, a non-porcine pancreatic enzyme replacement therapy (PERT). Liprotamase is under review by the U.S. Food and Drug Administration for the treatment of exocrine pancreatic insufficiency (EPI). Causes of EPI include cystic fibrosis, chronic pancreatitis, pancreatectomy and other conditions.Lilly

Patients with pancreatic insufficiency cannot properly digest and absorb fat, protein, and carbohydrates — preventing adequate nutrient absorption. PERT is a treatment involving the administration of three pancreatic enzymes. EPI often is associated with cystic fibrosis, a lifethreatening genetic disorder.

Cystic fibrosis affects approximately 30,000 children and adults in the United States and nearly 100,000 people worldwide. Approximately 90 percent of cystic fibrosis patients receive
pancreatic enzyme replacement therapy to improve nutritional status and bowel-related
symptoms related to pancreatic insufficiency.

Financial terms of the agreement are not being disclosed.

“The acquisition of Alnara provides Lilly with a promising entry into enzyme replacement therapy — an area with unmet medical needs as well as opportunities for novel compounds that
give patients additional treatment options,” said Bryce Carmine, executive vice president of Lilly and president of Lilly BioMedicines. “Alnara has been very successful in the development of liprotamase — as indicated by its recent submission to the FDA — and we look forward to partnering with Alnara’s experts during the regulatory review process.”

Alexey Margolin, Ph.D., chief executive officer of Alnara, said: “Our agreement with Lilly is an important development as we move liprotamase through FDA regulatory review. Lilly’s deep
expertise in the U.S. pharmaceutical business, including regulatory affairs and the development of innovative compounds that address unmet medical needs, created a natural fit and could allow
for opportunities in markets beyond cystic fibrosis. We look forward to finalizing the transaction and working together on next steps to bring liprotamase to patients.”

If approved, liprotamase will allow many patients to use significantly fewer pills compared to current treatment options. Treatments in the PERT class reduce malabsorption and enhance
nutrition in patients with EPI. Because it is not derived from a porcine source, liprotamase could provide the added benefit for patients of reduction in the risk of viral exposure. A pediatric
formulation of liprotamase also is in development.

About Liprotamase & Pancreatic Enzyme Replacement Therapy (PERT)

Liprotamase is an oral, non-porcine pancreatic enzyme replacement therapy designed to treat maldigestion, malabsorption and malnutrition as a result of exocrine pancreatic insufficiency associated with cystic fibrosis, chronic pancreatitis, pancreatic cancer, pancreatectomy and other pancreatic diseases. Patients with pancreatic insufficiency cannot properly digest and absorb fat, protein, and carbohydrates preventing adequate nutrient absorption. PERT is a treatment involving the administration of pancreatic enzymes, which in the case of liprotamase includes protease, amylase and lipase.

Results from an international, Phase 3 open-label, long-term safety study presented at the North American Cystic Fibrosis Conference in October, 2009 demonstrated the safety and nutritional benefits of liprotamase. The nutritional parameters measured during the study showed nutritional maintenance relative to the U.S. population, as well as a significantly reduced pill burden.

Eisai, Arena sign $1.37 B agreement for antiobesity drug LORCASERIN marketing


Companies Sign Marketing and Supply Agreement; Arena Eligible to Receive Over 30% of Eisai’s Net Sales and $1.37 Billion in Other Payments

Arena Pharmaceuticals, Inc. (Nasdaq: ARNA) today announced that Eisai Inc. will market lorcaserin for obesity and weight management in the United States following U.S. Food and Drug Administration (FDA) approval under the terms of a marketing and supply agreement between Arena Pharmaceuticals GmbH, a wholly owned subsidiary of Arena Pharmaceuticals, Inc., and Eisai. Lorcaserin, which Arena discovered and has developed for weight management, is intended for obese patients as well as overweight patients who have at least one weight-related co-morbid condition.

As part of the marketing and supply agreement, Arena has granted Eisai exclusive U.S. rights to commercialize lorcaserin. Arena will manufacture lorcaserin at its facility in Switzerland and sell finished product to Eisai for marketing and distribution in the United States.

“Through this agreement, we believe Eisai has an opportunity to bring a new option to market to address the significant and growing need for obesity treatments,” said Lonnel Coats, President and Chief Executive Officer of Eisai Inc. “Additionally, by building on our expertise and success in the primary care and specialty areas, with strong synergy in our gastrointestinal franchise, this arrangement for the marketing of lorcaserin will enable Eisai to establish a strong presence in the United States for the medical management of obesity.”

Under the terms of the agreement, Arena will receive an upfront payment of $50 million from Eisai and, upon regulatory approval and the delivery of product supply for launch, up to an additional $90 million in milestone payments. Arena will sell lorcaserin to Eisai for a purchase price starting at 31.5% of Eisai’s annual net product sales, and the purchase price will increase on a tiered basis to as high as 36.5% on the portion of annual net product sales exceeding $750 million. Arena is also eligible to receive $1.16 billion in one-time purchase price adjustment payments based on annual sales levels of lorcaserin and up to an additional $70 million in regulatory and development milestone payments.

“Execution of this commercial agreement is a major milestone in our plans for lorcaserin,” said Jack Lief, Arena’s President and Chief Executive Officer. “We believe in Eisai’s human health care mission to satisfy unmet medical needs and increase benefits to patients and their families. With Eisai, we have the right company to market lorcaserin in the United States, the right type of agreement to optimize lorcaserin’s medical and commercial potential and the shared recognition that it is the right time to enter into this agreement to prepare for launch following FDA approval.”

About Lorcaserin

Lorcaserin is a novel single agent that represents the first in a new class of selective serotonin 2C receptor agonists. The serotonin 2C receptor is expressed in the brain, including the hypothalamus, an area involved in the control of appetite and metabolism. Stimulation of this receptor is strongly associated with feeding behavior and satiety. Arena has patents that cover lorcaserin in the United States and other jurisdictions, which in most cases are capable of continuing into 2023 without taking into account any patent term extensions or other exclusivity Arena might obtain.

Phase 3 Program Overview

The pivotal Phase 3 clinical trial program, BLOOM (Behavioral modification and Lorcaserin for Overweight and Obesity Management) and BLOSSOM (Behavioral modification and Lorcaserin Second Study for Obesity Management), evaluated nearly 7,200 patients treated for up to two years. In both trials, lorcaserin was well tolerated and produced statistically significant weight loss. These double-blind, randomized, placebo-controlled trials evaluated obese patients, BMI 30 to 45, with or without co-morbid conditions and overweight patients, BMI 27 to 29.9, with at least one co-morbid condition, such as hypertension, cardiovascular diseases or glucose intolerance.

In addition to the pivotal program, Arena is evaluating lorcaserin for weight management in obese and overweight patients with type 2 diabetes in its BLOOM-DM (Behavioral modification and Lorcaserin for Overweight and Obesity Management in Diabetes Mellitus) trial. Results of BLOOM-DM are expected late this year, and Arena plans to file the results as a supplement to the New Drug Application (NDA).

Chiasma’s acromegaly drug gets FDA orphan drug status


The company plans a Phase III trial by the end of the year.acromegaly-214_21

by Shiri Habib-Valdhorn

Biopharma company Chiasma Inc. has been granted orphan drug status by the US Food and Drug Administration (FDA) for its investigational drug, Octreolin, an oral form of octreotide acetate for the oral treatment of acromegaly. Acromegaly is a hormonal disorder that results from an excess of growth hormone.

If a New Drug Application (NDA) is approved, Octreolin should qualify for seven years of market exclusivity, potential tax credits, and a waiver of the prescription drug user fee for the marketing application.

Chiasma has successfully completed a Phase I clinical study and plans initiating a Phase III trial by the end of the year.

Chiasma will submit an application for Orphan Medicinal Product Designation to the European Medicines Agency (EMA) shortly.

The pool of patients eligible for Octreolin treatment for acromegaly is estimated to be between 10,000 and 15,000 in the US and a similar number in Europe.

The company is also developing a drug for treating chronically high blood pressure via the liver.

Published by Globes [online], Israel business news – www.globes-online.com – on June 28, 2010

© Copyright of Globes Publisher Itonut (1983) Ltd. 2010

Stopping schizophrenia before it starts


  • New Israeli research suggests that schitzophrenia could be prevented if caught early enough.
  • If administered in the early-onset stages of the disorder, drugs used to treat schizophrenia may have the power to prevent it, according to Israeli researchers.

New research from Israel suggests that it may be possible to prevent schizophrenia if it can be caught before it fully manifests itself. The study, from Tel Aviv University (TAU), shows that early intervention could prevent the mind-altering disorder.

Prof. Ina Weiner of the department of psychology at TAU says: “The big question asked in recent years is if schizophrenia can be prevented.” Her response is that drugs like clozapine that are used to treat schizophrenia might, if administered during a subject’s adolescence, prevent the development of the disease in those predisposed to it. “Pharmacological treatments for schizophrenia remain unsatisfactory, so clinicians and researchers like myself have started to dig in another direction,” she says. Their results provide hope.

The onset of schizophrenia, which affects about 1.1 percent of the US population, is not easy to predict. Although it is associated with as many as 14 genes in the human genome, the prior presence of schizophrenia in the family is not enough to determine whether one will succumb to the mind-altering condition. The disease also has a significant environmental link.

Searching for biological cues prior to onset

Weiner explains that the developmental disorder, which usually manifests in early adulthood, can be triggered in the womb by an infection. But unlike developmental disorders such as autism, it takes many years for the symptoms of schizophrenia to develop.

In their study, recently reported in Biological Psychiatry, Weiner and her colleagues Dr. Yael Piontkewiz and Dr. Yaniv Assaf sought to discover biological cues that would help to trace the progression of the disease before symptoms manifested. “If progressive brain changes occur as schizophrenia is emerging, it is possible that these changes could be prevented by early intervention,” she says. “That would revolutionize the treatment of the disorder.

“We wondered if we could use neuro-imaging to track any early-onset changes in the brains of laboratory animals,” Weiner relates. Then she says, the scientists asked: “If so, could these changes and their accompanying schizophrenia-like symptoms be prevented, if caught early enough?”

Weiner and her team gave pregnant rats a viral mimic known to induce a schizophrenia-like behavioral disorder in offspring. This method simulates maternal infection in pregnancy, which is a well-known risk factor for schizophrenia. Weiner demonstrated that the rat offspring were normal at birth and during adolescence. But in early adulthood, the animals, like their human counterparts, began to show schizophrenia-like symptoms.

Arresting brain deterioration

As she examined brain scans and behavior, Weiner found abnormal development of the lateral ventricles and the hippocampus in those rats with “schizophrenia.” Those that were at high risk for the condition could be given drugs to treat their brains, she determined.

Following treatment with risperidone and clozapine, two commonly used drugs to treat schizophrenia, brain scans performed at the Center for Computational Neuro-Imaging at TAU showed that the lateral ventricles and the hippocampus regained a healthy size.

“Clinicians have suspected that these drugs can be used to prevent the onset of schizophrenia, but this is the first demonstration that such a treatment can arrest the development of brain deterioration,” Weiner says, adding that the drugs work best when delivered during the rats’ “adolescent” period, several months before they reach full maturity.

Currently, anti-psychotics are prescribed only when symptoms are present. Weiner and her colleagues believe that an effective non-invasive prediction method (following the developmental trajectory of specific changes in the brain), coupled with a low dose drug taken during adolescence, could stave off schizophrenia in those most at risk.

Weiner has already begun research to determine the point at which changes in the brain can be detected.

Estrogen as ammo against schizophrenia

In a related development, Weiner has also discovered that the female hormone estrogen may work as a protective agent in menopausal women vulnerable to schizophrenia.

While estrogen replacement therapy has long been a controversial treatment for the symptoms of menopause, a TAU study shows that it may have a positive effect in women who are at risk for schizophrenia.

“Antipsychotic drugs are less effective during low periods of estrogen in the body, after birth and in menopause. Now our pre-clinical findings show why this might be happening,” says Weiner. “Our research links schizophrenia and its treatment to estrogen levels.”

Weiner and her doctoral student Michal Arad have reported findings suggesting that restoring normal levels of estrogen may work as a protective agent in menopausal women vulnerable to schizophrenia.

Their work, based on an animal model of menopausal psychosis, was recently reported in the journal Psychopharmacology. In their study, Weiner and Arad removed the ovaries of female rats to induce menopause-like low levels of estrogen and showed that this led to schizophrenia-like behavior. The researchers then tried to eliminate this abnormal behavior with an estrogen replacement treatment or with the antipsychotic drug haloperidol.

Estrogen replacement therapy effectively alleviated schizophrenia-like behavior but haloperidol had no effect on its own. Haloperidol regained its effect in these rats when supplemented by estrogen.

BIND Biosciences raises a new round for its nanotechnology drug-delivery anti-cancer platform


Scott Minick, CEO of BIND Biosciences

BIND Biosciences, Inc. (BIND), a privately held biopharmaceutical company developing best in class therapeutics based on its proprietary targeted nanotechnology platform, announced today that it has secured a $12.4 Million Series C-1 financing.

This financing included all of BIND’s current investors as well as a new venture investor, and private investors. BIND’s Medicinal NanoengineeringTM approach enables the development of targeted polymeric nanoparticle-based therapeutics that deliver high drug concentrations to diseased cells and tissues, resulting in increased efficacy and reduced toxicity of existing and new drug compounds. The proceeds of this financing will be used to conduct initial clinical trials on BIND’s lead product candidate, BIND-014, a nanoparticle cancer therapeutic targeted to a clinically-validated solid tumor antigen, and to advance a second product candidate toward the clinic.

“The support from new and existing investors to take our lead product, BIND-014, into the clinic this year and move our second product towards the clinic next year is a significant step forward for BIND,” said Scott Minick, President and Chief Executive Officer of BIND. “We are pleased that investors recognize BIND’s achievements and the value of our platform and products. We look forward to translating this investment into therapeutics that will benefit patients, with a particular focus on nanoparticle-based cancer drugs in the near term.”

About BIND Biosciences

BIND Biosciences, Inc., is a biopharmaceutical company leveraging its proprietary Medicinal Nanoengineering platform to produce best in class drugs to provide significant improvement in the treatment of patients with serious diseases. BIND’s platform enables the design, engineering and manufacturing of therapeutic targeted nanoparticles with unprecedented control over drug pharmacokinetics, biodistribution and cell- or tissue-specific targeting. Medicinal Nanoengineering complements medicinal chemistry to enable predictable, cost effective and rapid development of breakthrough products with superior efficacy and safety profiles. Product opportunities include enabling or expediting the development of pipeline molecules as well as improving performance, expanding indications or life cycle extension for mid- and late-stage products. BIND’s initial product development efforts are in the areas of oncology, cardiovascular disorders, inflammatory disease and RNAi therapeutics. BIND’s lead program, BIND-014, targets a surface protein upregulated in solid tumors and is planned to enter clinical development in 2H 2010.

BIND was founded in 2006 by two pioneers in the field of therapeutic targeted nanoparticles, Dr. Robert Langer, MIT David H. Koch Institute Professor, and Dr. Omid Farokhzad, Harvard Medical School Associate Professor.

Sanofi Aventis Recruiting more than 4000 individuals for a Phase II Dengue Clinical Trial


An advisory the Centers for Disease Control and Prevention issued in late May announced that dengue has returned the continental United States, for the first time in more than 65 years.dengue

The upsurge is not unexpected. Experts say more than half the world’s population will be at risk by 2085 because of greater urbanization, global travel and climate change. Over the past 30 years, a global outcry against using the pesticide dichlorodiphenyltrichloroethane, or DDT, has led to the resurgence of the mosquito, a voracious consumer of human blood and carrier of infectious disease.

Epidemics have become routine in Latin America, a continent on the verge of becoming highly endemic. Outbreaks are today raging in Brazil, Guatemala and other nations. Thailand, within a week of its annual dengue season this year, has already reported 18,000 cases and 20 deaths, according to the Ministry of Public Health.

As the virus spreads in the tropics, experts are continuing to push toward an ultimate solution for the mosquito-borne illnesses: an effective and affordable vaccine. There are no drugs for the disease.

Jean Lang, a doctor who heads the vaccine division of the deep-pocketed pharmaceuticals company Sanofi Pasteur Inc., last month presented the world’s most advanced effort to vaccinate against dengue to a room full of industry insiders in Chicago. The market for a vaccine is huge, with experts pegging sales at between $700 million and $1 billion per yearIn comparison, the company’s top-selling drug right now, an insulin injection called Lantus, nets $3.7 billion per year.

“If everything goes well, we will have phase 3 trials on an industrial scale by the end of the year,” Lang remarked. He spoke of nearly 100 million people worldwide getting the disease and 25,000 people dying in tropical countries per year.

But the virus was closer than that. In April, a 41-year-old man in Key West, Fla., was admitted to a hospital, complaining of fever and blood in his urine, according to CDC. Tests revealed that he had antibodies to the dengue virus, which is mild in its most prevalent form. In more severe versions of the illness, called dengue hemorrhagic fever and the dengue shock syndrome, the virus can kill by significant internal bleeding.

Since August 2009, U.S. doctors have diagnosed 28 people with dengue, according to CDC. They had all caught it in Florida.

‘Very optimistic’ about new vaccine

Sanofi’s is the most advanced vaccine against the life-threatening disease carried by the tiger mosquito, Aedes aegypti. The company has recruited 4,000 children ages 4 to 11 in Thailand who will receive three shots of a vaccine that should protect them, if all goes well. Final trials will be conducted in an even larger group. Since vaccine development is a minefield with most attempts dying in the clinical trial phase, success is not guaranteed.

Dengue is a difficult candidate to design a vaccine for, Lang explained. It belongs to the flavivirus category of microbes, so named after the virus that causes yellow fever. And there are actually four different viruses, and each can activate a separate immune response in the body. A person who is vaccinated needs to be able to ward off all the virus types.If the vaccine acts against only one virus, an infection by a different variety can result in the more severe dengue hemorrhagic fever or shock syndrome.

“I’m very optimistic that Sanofi’s product is going to work,” said Lt. Col. Stephen Thomas, a U.S. Army physician at the Armed Forces Research Institute of Medical Sciences in Thailand, which is working with drugmaker GlaxoSmithKline (GSK) on a different vaccine.

“They’ve given the vaccine to thousands of people so far and very carefully assessed safety, and there’s been no major safety signal so far,” Thomas said. Other experts in the field agree.

The United States’ investment in dengue started after World War II when it saw children dying of a mysterious hemorrhagic fever in Thailand. Army men and women were also contracting the disease abroad. It soon handed over research to its infectious disease unit, and the Army has been collaborating with various universities and pharmaceutical groups since then.

The latest partnership is with GSK, which is examining results from a phase 2 clinical trial to be concluded in December, according to Thomas.

“There are over 110 countries where transmission can occur,” Thomas said. “Lots of countries and governments would be very interested in purchasing a dengue vaccine.”

Risky research

For most of the time during the history of research into the disease, there has been no animal model for testing. While monkeys can get infected by the virus, they do not fall sick from it like humans do. This means that any advances in science would have to be tested in people. The pitfalls of an unsafe vaccine would be huge, and larger leaps in science would have to be ignored for smaller but safer attempts.

Despite the risks, a few efforts have advanced. Sanofi’s is a novel attempt at engineering a cure in a field that has been around for half a century.

The vaccine is genetically modified, a mishmash of the genes of dengue pasted into the backbone of the yellow fever virus. The viruses so formed are mutated and weak.

Where injecting the normal viruses into a human can trigger a full-blown case of dengue, the weakened viruses are overtaken by the immune system. The body learns from the attack and makes antibodies that ward off future infections by naturally occurring viruses. The company expects the vaccine to be launched in 2015.

In comparison, GSK’s vaccine is not man-made, but a weakened version of the naturally occurring virus.

Other initiatives include one by the National Institutes of Health, which is entering phase 1 trials, according to Anna Durbin at the department of international health at the Johns Hopkins Bloomberg School of Public Health.

Studies flourish with disease

Developing vaccines for infectious diseases that primarily afflict low- and middle-income countries has traditionally been a low priority. But with the re-emergence of the disease in the Western Hemisphere, a $55 million increase in funding by the Bill and Melinda Gates Foundation in 2003, and interest from major pharmaceutical companies, research has flourished, said Lt. Col. Thomas.

The recent upsurge in disease in the Americas has been caused by a number of factors, including careless vector control since the eradication of the mosquito in the 1970s, according to Knowlton. A report she did for the Natural Resources Defense Council found that since 1995, rates of dengue fever have increased by more than 100 percent in Bolivia, Costa Rica, El Salvador, the Caribbean and Puerto Rico.

“The mosquitoes love to live in close proximity to people and like clean water that people need,” Knowlton said.

The insect’s preferred habitat — flower pot liners, stagnant but clean water stored in parched cities, rubber tires and the like — have exploded in recent years as people flock to cities. And new infections have tended to result in more severe fevers as waves of adults catch the disease the second time around. The World Health Organization is contemplating revising its definitions of dengue hemorrhagic fever since even primary fevers can sometimes be quite severe, according to Durbin of Johns Hopkins.

Viral development is faster at warmer temperatures and mosquitoes survive for longer, according to Paul Epstein, associate director of the center for health and the global environment at Harvard Medical School.

“As things continue to warm, there’ll be more breaches of our shores by tropical illnesses,” Epstein said.

University of Maryland Baltimore plans $675M biotech park expansion


University of Maryland BioparkUniversity of Maryland Baltimore leaders are asking the city’s architecture review board to approve a $675 million expansion of the UMB BioPark–a move that would triple the size of the planned project. At the moment the site has two research buildings with 470,000 square feet of space, and a third building will open its doors later this year. The BioPark already counts Alba Therapeutics, Gliknik, FASgen, Biomere, and Fyodor Biotechnologies among its tenants, according to the Baltimore Business Journal.

Two years ago, Maryland Governor Martin O’Malley announced plans to invest $1.3 billion in the state’s bioscience industry by the year 2020. The state’s biotech leaders hope the massive expansion will help it compete with biotech powerhouses like San Francisco and Boston for tenants.

Construction of yet another multi-tenant building is expected to begin later this year, and BioPark planners are on the hunt for tenants for the new space. “If I said we were putting every ounce of energy into finding tenants for that building, it would be an understatement,” Jane Shaab, the biopark’s senior vice president, told the Journal. “That is the focus right now.” The BioPark expansion will boast 11 research buildings upon completion in 2020.

Gilead Sciences Acquires CGI Pharmaceuticals for up to $120 Million


Norbert W. Bischofberger

Norbert W. Bischofberger, PhD, Gilead’s Executive Vice President, Research and Development and Chief Scientific Officer.

 

Gilead Sciences, Inc. (Nasdaq:GILD) and CGI Pharmaceuticals, Inc., a privately-held, development-stage pharmaceutical company focused on small molecule chemistry and kinase biology, today announced the signing of a definitive agreement pursuant to which Gilead will acquire CGI.

Under the terms of the agreement, Gilead will acquire CGI for up to $120 million, the majority as an upfront payment and the remaining based on clinical development progress, all of which will be financed through available cash on hand. Gilead anticipates that the deal would close in the third quarter of 2010, subject to satisfaction of certain closing conditions. After closing, CGI will continue operations in Branford as a wholly-owned subsidiary of Gilead.

CGI has generated a library of proprietary small molecule kinase inhibitors. The lead preclinical compound from this library targets spleen tyrosine kinase (Syk) and could have unique applications for the treatment of serious inflammatory diseases, including rheumatoid arthritis.

“The acquisition of CGI represents a unique opportunity to expand our research efforts in an interesting and promising area of drug discovery,” said , PhD, Gilead’s Executive Vice President, Research and Development and Chief Scientific Officer. “CGI has established itself in the area of protein kinase biology and small molecule discovery, and the company’s scientific leadership and expertise represents a strong strategic fit with Gilead’s existing research organization. We look forward to advancing compounds in CGI’s portfolio toward clinical development.”

“We are pleased to join the Gilead organization and look forward to partnering with the company to deliver on the promise of selective kinase inhibitors in our proprietary library of compounds,” said Mark Velleca, MD, PhD, Founder and Senior Vice President of CGI. “We are confident that Gilead’s knowledge and experience developing small molecule candidates for a range of clinical indications will be instrumental in helping to progress our compounds toward clinical development for diseases where tremendous unmet medical need exists.”

About CGI Pharmaceuticals, Inc.

CGI Pharmaceuticals, Inc. is a private, development-stage pharmaceutical company that has leveraged its small molecule chemistry and kinase biology expertise to discover and develop an innovative pipeline of small molecule therapeutics for multiple oncology and immunology-based indications. CGI’s investors include: MPM Capital, Flagship Ventures, Vector Fund Management, Coastview Capital, Vantage Point Venture Partners, Lilly BioVentures, RiverVest Venture Partners, CHL Medical Partners, Connecticut Innovations, Oxford Bioscience Partners, and Emerging Technology Partners. CGI’s corporate headquarters and research laboratories are located in Branford, Connecticut. For additional information about the company, please visit: www.cgipharma.com.

About Gilead Sciences

Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company’s mission is to advance the care of patients suffering from life-threatening diseases worldwide. Headquartered in Foster City, California, Gilead has operations in North America, Europe and Australia.

Sanofi signs $375M deal with Metabolex for diabetes target


DiabetesHayward, CA-based Metabolex is on a roll, inking its second deal this week. The developer has secured an undisclosed upfront payment and up to $375 million from Sanofi-Aventis for rights to an experimental diabetes treatment. The two companies will collaborate on MBX-2982, a potent selective orally active GPR119 agonist which has completed three Phase I clinical studies and is currently a Phase II clinical study in patients with Type 2 diabetes. The drug helps boost both insulin and a hormone called GLP-1, according to BusinessWeek. It may also promote weight loss.

Metabolex and Sanofi-Aventis announced today that they have entered into a global license and development agreement for the research, development, manufacture and commercialization of small molecules that modulate the G-protein coupled receptor 119 (GPR119), a receptor in the gut and pancreas that interacts with bioactive lipids to stimulate glucose-dependent incretin and insulin secretion.  Agonists of GPR119 represent a first-in-class oral treatment for type 2 diabetes that function through a unique dual mechanism of action.  First, they act directly on the pancreatic beta cell to increase insulin secretion.  In addition, they stimulate release of the incretin GLP-1 from the intestines. This unique dual action may offer improved glucose homeostasis over existing diabetes therapies, with the potential for weight loss and improved islet health.

The agreement includes MBX-2982, a potent selective orally active GPR119 agonist discovered by Metabolex.  MBX-2982 has completed three Phase 1 clinical studies and has consistently shown clinically meaningful glucose reductions in healthy volunteers and subjects with impaired glucose tolerance.  In all of these studies, MBX-2982 was found to be safe and well tolerated.  MBX-2982 is currently in a multi-national 28-day Phase 2 clinical study in patients with type 2 diabetes.

Under this agreement, Metabolex will receive an upfront payment and will be eligible to receive development, regulatory, and specified commercial milestones that total as much as $375 Million.  Metabolex is also eligible to receive royalties on worldwide sales of marketed products.

“We are excited about working with Sanofi-Aventis on this exciting new therapy for type 2 diabetes,” said Harold Van Wart, president and CEO of Metabolex.  “Sanofi’s clear strategic commitment to the field of diabetes makes them the ideal partner to maximize the significant potential of this compound and provide an exciting new therapeutic option for diabetes patients.”

The license agreement is subject to antitrust clearance under the Hart-Scott-Rodino Antitrust Improvements Act.

About Metabolex

Metabolex is a privately-held biopharmaceutical company focused on the discovery and development of proprietary new medicines for the treatment of metabolic diseases, with an emphasis on type 2 diabetes.  The company has four clinical-stage compounds:  MBX-2982, which has completed three Phase 1 trials and is currently enrolling patients in a Phase 2 study; MBX-102, which has completed four Phase 2 trials; MBX-2044, which has completed a Phase 2a trial; and MBX-8025, which has completed a Phase 2 trial in patients with dyslipidemia.

Protalix Initiates A Phase I Clinical Trial Of Acetylcholinesterase For Biodefense Indications


Protalix BioTherapeutics, Inc. (NYSE-Amex: PLX) announced that it has initiated a phase I clinical trial of PRX-105, the Company’s plant cell expressed pegylated recombinant human acetylcholinesterase product candidate in development for biodefense indications. The trial is designed to study the safety of PRX-105 by administering a bolus intravenous injection of PRX-105 in healthy volunteers. The U.S. Food and Drug Administration (FDA) and the Israeli Ministry of Health have each accepted the Company’s exploratory Investigational New Drug application to commence the phase I clinical trial of PRX-105. Pre-clinical studies have previously indicated that PRX-105 successfully protects animals exposed to organophosphate nerve gas agent analogs, in both the prophylactic and post-exposure settings. In addition, the safety of PRX-105 has been demonstrated in a well-controlled study in rodents performed under good laboratory practices.

Before applying for marketing approval from the FDA and comparable foreign regulatory authorities, the Company will be required to perform additional safety studies in healthy volunteers, as well as additional studies in animals. Efficacy trials of PRX-105 in humans (phase II and phase III) are not required given the nature of the indication for which PRX-105 is being developed.

Nerve gas agents, such as organophosphates, bind to, and inhibit, the action of acetylcholinesterase, an endogenous enzyme that breaks down the neurotransmitter, acetylcholine, in humans. The loss of the acetylcholinesterase function results in an accumulation of toxic levels of acetylcholine, which has deleterious effects on major organ systems, including the heart, lung and central nervous system. PRX-105 acts as a bioscavenger of the organophosphates that affect the acetylcholinesterase, thereby causing a re-balancing of acetylcholine levels.

“We are excited that a second product candidate produced through our ProCellEx™ protein expression system has advanced to the clinical stage,” said Dr. David Aviezer, President and Chief Executive Officer of Protalix. “The treatment options currently available to victims of nerve gas attacks are limited and current rescue therapies have significant, life threatening side effects which give rise to the urgent need for an alternative biological solution, as recently indicated by U.S. government agencies.”

The PRX-105 program is being conducted in collaboration with Professor Hermona Soreq, from the Hebrew University in Jerusalem, Israel, a world leader in the field of acetylcholinesterase research, and based on patents that were licensed to Protalix Ltd. by Yissum, the Technology Transfer Company of the Hebrew University. “The acetylcholinesterase project is important project to me, both as an inventor and as a scientist, as Protalix is developing the acetylcholinesterase in its facility in Carmiel, Israel, and the protein appears to be available for use for multiple clinical needs, especially in the neurological degenerative disease area,” said Professor Soreq.

The Company is in discussions with both civil and military agencies in the United States and Israel with respect to this project.

BiolineRX deal with Cypress Bioscience for its Schizophrenia drug candidate worth up to $365m


Source: BioJerusalem

BiolineRX Ltd. (TASE:BLRX) has granted an out-license to Cypress Bioscience Inc. (Nasdaq: CYBP) for the company’s BL-1020 drug for the treatment of schizophrenia in the US, Canada, and Mexico.

Cypress has exclusive rights to complete clinical trials and regulatory procedures of BL-1020, and will bear the full costs in these clinical trials and regulatory procedures, as well as production and marketing of the drug in the territory. The company says that these costs will, by their nature, cost hundreds of millions dollars.Biolinerx

BiolineRX anticipates up to $365 million in payments from Cypress under the licensing agreement, not including royalties on sales. BiolineRX will receive $30 million upfront payment when the contract is closed; up to $250 million in milestone payments related to the development and approval of the drug, including use of the drug for other illnesses, and positive results of the clinical trials; and up to $85 million in milestone payment relating to the sale of the drug.

In addition to these payments, BiolineRX expects net royalties on sales of BL-1020 in Cypress’s territory of 12-18% of annual sales.

BiolineRX will pay the BL-1020 license-holder part of the proceeds from the out-license.

Closing of the deal is subject to approval by the Office of the Chief Scientist, which has supported development of BL-1020.

BiolineRX’s share price rose 12.8% in morning trading on the TASE to NIS 4.72, giving a market cap of NIS 580 million.

GW Pharmaceuticals has finally won UK approval for Sativex


sativexAfter a long and complex R&D odyssey, GW Pharmaceuticals (GWP) has finally won UK approval for Sativex, a drug derived from cannabis that can now be used to treat spasticity in MS patients.

GW had hoped to get an approval in Britain back in 2003 but faced a long series of regulatory hurdles in its quest. Up until now GW has had to content itself with a 2005 approval in Canada. But Europe appears to be opening up. GW says that Spain appears ready to hand out an approval soon and other European nations are likely to follow suit. GW and Bayer–which now owes GW a $15 million milestone payment–will market the drug in the UK with Almirall taking the reins in Spain. The approval helped buoy GW’s shares by about eight percent, according to Reuters, which broke the news.

An even bigger market could be opened up if GW wins an approval to use Sativex to treat cancer pain. Analysts say that a European approval for MS on top of the Canadian market would generate about 121 million pounds in annual sales while a cancer approval on the continent would be worth close to $500 million a year in sales.

GW has focused on the cancer pain indication for its application to the FDA. In March the developer announced positive Phase IIb cancer pain data  with its U.S. partner Otsuka. Researchers are planning a Phase III trial for cancer pain.

Roche diabetes drug taspoglutide delayed up to 18 month


insulineRoche has delayed development of its potential blockbuster type 2 diabetes drug taspoglutide for up to 18 months due to hypersensitivity problems observed in trial subjects, including skin reactions and digestive symptoms. Heart and respiratory events were also observed in some patients.

Roche will use the additional time to identify patients who are sensitive to the treatment and remove them from clinical trials. The Swiss drugmaker, which is developing the once-weekly injection in conjunction with French company Ipsen, had originally planned on filing for approval in 2011. A Jefferies industry analyst told Reuters that an approval may not come until 2014.

“A delay of 12 to 18 months is not good,” Andrew Weiss, an analyst at Bank Vontobel, told BusinessWeek. “It’s an important drug for Roche and they need it on the market to balance out the oncology franchise, which is starting to slow down.” Cancer blockbusters Rituxan, Herceptin and Avastin make up 50 percent of the drugmaker’s sales.

When positive results from a large Phase III trial were revealed earlier this year, analysts projected the drug could reach $2.8 billion a year in sales. But tolerability problems unveiled at a recent diabetes conference, in conjunction with this delay, have cause industry experts to adjust taspoglutide’s market potential to just $490 million in 2014. If approved taspoglutide will compete with Novo Nordisk’s Victoza, which is already on the market, and Amylin’s Bydureon.

Bayer and OncoMed Announce Strategic Alliance to Develop Anti-Cancer Stem Cell Therapeutics


Collaboration Focuses on the Discovery and Development of Multiple Antibody, Protein and Small Molecule Agents Targeting the Wnt Pathway

Cancer stem cell

Bayer Schering Pharma AG and OncoMed Pharmaceuticals, Inc., today announced a global strategic alliance to discover, develop and commercialize novel anti-cancer stem cell therapeutics targeting the Wnt signaling pathway.  Cancer stem cells are a subset of tumor cells believed to play a significant role in the establishment, metastasis and recurrence of cancer and agents targeting the Wnt pathway have the potential to be developed as pan-tumor drugs.  The strategic alliance provides Bayer with the option to exclusively license antibody and protein therapeutic product candidates at any point up to the completion of Phase I testing.  In addition, Bayer and OncoMed will share technology and know-how to discover and develop small molecule inhibitors of the pathway.

At Bayer, we recognize the high unmet medical need for cancer treatments.  This collaboration with OncoMed demonstrates our commitment to developing new and innovative treatment options,” said Prof. Andreas Busch, Head of Global Drug Discovery and Member of the Board of Management at Bayer. “The development of anti-cancer stem cell therapeutics together with OncoMed is a highly innovative approach with the potential to perfectly complement our oncology portfolio.  Anti-cancer stem cell research could turn out as one of the missing pieces in today’s cancer therapy.”

“Our alliance with Bayer represents a major opportunity to discover and develop an entirely new class of anti-cancer stem cell therapeutics with one of the leading pharmaceutical companies in the world.  Bayer shares our vision for the potential of anti-cancer stem cell therapeutics, and we look forward to working closely with them,” said Paul J. Hastings, President and CEO of OncoMed.  “OncoMed has established a rich pipeline of product candidates targeting a number of critical cancer stem cell pathways.  Through this collaboration, we will gain significant additional funding to support the discovery and development of therapeutics targeting the Wnt pathway, as we continue, with our already strong cash position, and our other sources of collaborative revenue to fully finance and advance all of our programs for years to come.”

Under the terms of the agreement, Bayer and OncoMed will develop antibodies, protein therapeutics, and small molecules as potential novel anti-cancer stem cell therapeutics targeting the Wnt signaling pathway.  In addition to an upfront payment of $40 million, OncoMed is eligible to receive cash payments for product candidates that Bayer options and possible additional payments upon achievement of certain development and commercialization milestones.  The collaboration could potentially include up to five compounds.  The agreement includes potential significant near-term milestone payments from Bayer.  For each biotherapeutic or small molecule drug candidate successfully developed through Phase III clinical trials and regulatory approval, OncoMed’s payments could total up to $387.5 million (biotherapeutic drug) and $112 million (small molecule drug) per program, already including net sales milestones.

OncoMed will utilize its proprietary human cancer stem cell models to discover and advance three potential first-in-class antibody and protein therapeutics into clinical testing and through Phase I studies.  Bayer receives an option to exclusively license antibody and protein therapeutic product candidates at any point up to the completion of Phase I testing.  Following option exercise, Bayer will lead development and commercialization of licensed product candidates and will have rights to commercialize approved products in all markets.  OncoMed will be eligible to receive double-digit royalties on net product sales.  The agreement contains provisions under which OncoMed may co-develop biologic therapeutics with Bayer.  The collaboration includes for example OncoMed’s lead Wnt pathway antibody, [OMP-18R5], which is intended to enter clinical testing in 2011.

In addition to the biologics approach, Bayer will use its in-house expertise and lead the discovery and development of small molecule compounds as therapeutic candidates modulating Wnt signaling.  OncoMed will assist Bayer in the evaluation and advancement of such candidates by providing its proprietary assay technology and in vitro/in vivo profiling of the compounds.  OncoMed will be eligible to receive single-digit royalties on net product sales.

About Cancer Stem Cells and the Wnt Signaling Pathway

Cancer stem cells, a small, resilient subset of cells found in tumors, have the capacity to self-renew and differentiate, leading to tumor initiation and driving tumor growth, recurrence and metastasis.  Also referred to as “tumor-initiating cells,” these cells were first discovered by OncoMed’s scientific founders in breast cancer and have subsequently been identified in many other types of solid tumors, including cancer of the head and neck, lung, prostate, pancreas, and glioblastoma.  Cancer stem cells appear to be preferentially resistant to both standard chemotherapy and radiotherapy.  OncoMed’s strategy is to improve cancer treatment by specifically targeting the key biologic pathways which are thought to be critical to the activity and survival of cancer stem cells.  OncoMed’s antibody therapeutics target cancer stem cell proteins and have the potential to be developed against a range of solid tumor types.

The Wnt signaling pathway is one of several identified by OncoMed as an important therapeutic target in halting cancer stem cell activity.  In preclinical studies of monoclonal antibody drug candidates that target Wnt signaling, OncoMed scientists have observed broad-spectrum anti-tumor and anti-cancer stem cell activity in a number of solid tumor types.

Pfizer running for first biological approved biologic for pain.


Pfizer ran the table in a late-stage study of tanezumab, a protein inhibitor that the pharma giant is touting as a leading contender to go on to become the world’s first approved biologic for pain.

The pharma giant recruited 690 patients for the trial who suffered from chronic knee pain from osteoarthritis but were either unable to take an NSAID pain therapy or its Cox-2 inhibitor Celebrex or didn’t benefit sufficiently from the meds. Patients in all three dose groups–2.5 mg, 5 mg and 10 mg–reported a statistically significant reduction in pain compared with a placebo, according to Reuters. And the patients also demonstrated a significant improvement in physical function as well as higher scores for feeling better than before therapy. The Phase III study results are being presented at the European League Against Rheumatism meeting in Rome.

“What we’ve seen so far in terms of Phase II trials and this first Phase III trial has impressed upon us that this drug has some extraordinary efficacy benefits,” study leader Mark Brown tells Reuters.

Pfizer has high hopes for tanezumab, an antibody that was selected as one of its top drug prospects during a pipeline review in the spring of 2009. The antibody targets nerve growth factor and had already registered promising data in mid-stage trials. The fresh set of positive data is good news for Xoma, which licensed antibody technology used in developing the tanezumab program and stands to earn royalties in the event of an approval.

Pfizer Establishes Rare-Disease Research Unit


By: Erik Greb

Jose Carlos Gutierrez-Ramos, SVP Research and Development, Biotherapeutics, Pfizer

This week, Pfizer (New York) created a new research unit within its Worldwide Research and Development division that will focus on rare diseases. The new unit will expand the company’s presence in rare-disease research and seek to discover medicines for diseases that affect fewer than 200,000 patients. Pfizer’s Rare Disease Research Unit will pursue treatments in all therapeutic areas, and the company will collaborate with patient-advocacy groups as it develops the unit’s research plan. The establishment of the new research unit is part of Pfizer’s strategy to use its scientific and technological resources to find new treatments for patients with large unmet medical needs.

Edward Mascioli, most recently the founder and CEO of private-equity firm Dapis Capital, will lead the Rare Diseases Research Unit. Mascioli gained clinical-development experience as vice-president of clinical affairs at Peptimmune (Cambridge, MA) and as senior medical director at Parexel International (Waltham, MA). Mascioli, who also has a background in business development, will be based in Cambridge, Massachusetts, and will report to Jose Carlos Gutierrez-Ramos, Pfizer’s senior vice-president of biotherapeutics research and development.

“We are very excited about our new Rare Diseases Research Unit,” said Gutierrez-Ramos in a company press release. “We are coupling Pfizer’s existing experience in rare diseases such as hemophilia with our advanced protein technologies, resources, and world-class scientific team to focus on becoming a driving force in rare-disease research. Pfizer has a long history in discovering, developing, and commercializing medicines that treat rare diseases and we are hopeful that this research unit will lead to additional new medicines for patients suffering from devastating illnesses for which there is no cure.”

The National Organization for Rare Disorders (NORD) is “very happy that Pfizer is establishing a Rare Diseases Research Unit,” said Peter L. Saltonstall, the group’s president and CEO, in the Pfizer press release. “Approximately 30 million Americans, 30 million Europeans, and millions more around the world have rare diseases and, for most of those people, there is no specific treatment. As the voice of the US rare-disease patient community, NORD applauds Pfizer’s commitment to expanding its research with the goal of developing new treatments for this medically underserved population.”

Although more than 6000 diseases are classified as orphan diseases, fewer than 10% of them are directly targeted by specific drugs. The pharmaceutical industry traditionally has invested little in rare-disease research, and its scientific advances in this field have proceeded slowly as a result.

Pfizer’s interest in rare diseases was first manifest in December 2009, when the company licensed the worldwide rights to taliglucerase alfa, a product that treats the genetic disorder Gaucher disease, from Protalix Biotherapeutics (Karmiel, Israel). With that deal, Pfizer became a competitor of Genzyme (Cambridge, MA), which markets Cerezyme as a treatment for Gaucher disease.

Pre-empting multiple sclerosis


“Those who will develop MS will show a different blood signature from those who will not,” Prof. Anat Achiron, director of the Multiple Sclerosis Center at Sheba Medical Center.

Multiple sclerosis (MS) has devastated the lives of two million people around the world. The disease is more prevalent in cold climates and attacks twice as many women as men. There is currently no cure. Now, research from Israel may pave the way for a diagnosis before symptoms appear and debilitation sets in. Earlier diagnosis of the disease will allow earlier medical intervention – and perhaps even lead to a cure.

Prof. Anat Achiron of Tel Aviv University’s Faculty of Medicine and director of the Multiple Sclerosis Center at Sheba Medical Center has uncovered a new way of detecting MS biomarkers in the blood. Her findings were published in the journal Neurobiology of Disease and are expected to pave the way for a diagnosis of MS before symptoms can appear, allowing for earlier treatment.

MS attacks the central nervous system and eventually renders most patients disabled. The National MS Society estimates that there are currently about 400,000 cases in the US. In Israel there are an estimated 5,000 cases, according to the Israel Multiple Sclerosis Society.

“We are not yet able to treat people with MS to prevent the onset of the disease but knowledge is power,” Achiron says. “Every time we meet a new patient exhibiting symptoms of MS, we must ask ourselves how long this has been going on. We can diagnose MS by brain MRI, but we’ve never been able to know how ‘fresh’ the disease is,” she says.

Identifying MS a decade before symptoms appear

If doctors can predict the onset of MS early enough, intervention therapies using immunomodulatory drugs such as Copaxone (produced by Israel’s Teva Pharmaceuticals) or beta-interferon drugs that stave off MS symptoms might be used.

“We theorized that if we looked at the gene expression signature of blood cells in healthy people, we could look for possible biological markers that characterize those who subsequently developed MS,” Achiron explains.

Examining blood samples of 20 19-year-old Israelis who were inducted into the army as healthy soldiers, and the nine of them who later developed MS, Achiron and her team at Sheba were able to use a “high throughput analysis” with more than 12,000 gene transcripts expressions. The screening compared similarities and differences in the blood of those who developed MS and those who did not, eventually establishing biological markers.

“Those who will develop MS will show a different blood signature from those who will not,” states Achiron. “When we compared the gene expression signatures, we saw a similar pattern of the same working biological processes.”

These early genetic markers may now be used to test for MS up to nine years before healthy young adults start developing symptoms. And because MS is thought to have a genetic component and a tendency to be found in siblings, Achiron foresees that the biomarkers will be used as a tool for brothers and sisters of patients.

Clues for early intervention

Why test in advance of a cure? “The idea is that we’ll know more about the genetics of MS through this new discovery, with the hope that early intervention therapies may be more effective, and help advance medicine toward a cure,” responds Achiron. This new insight into who will develop MS in the future is a first step on the path of finding a cure to the disease.

By the time a person notices symptoms, significant and irreversible nerve damage has already occurred. MS is classified as an autoimmune disease that afflicts the brain and spinal cord. Symptoms vary, because the location and severity of each attack can be different, and until now, there has been no way of knowing who it will strike.

The disease causes the body’s immune system’s T cells to mistakenly regard the myelin sheath around our body’s neurons as foreign, so the immune system starts attacking the sheath, causing neurons to short circuit.

Two of the most important drugs that shorten multiple sclerosis attacks were developed in Israel, and Tel Aviv University is considered a center of excellence in MS research. Other researchers in the study include David Magalashvili and Anna Feldman of Tel Aviv University, and Drs. Itamar Grotto and Ran Balicer of the Israel Defense Forces.

Cleveland Clinic breast cancer vaccine could eliminate disease


A vaccine to prevent breast cancer being developed by Cleveland Clinic researchers has shown “overwhelmingly favorable results” in animals and could be on its way to conquering the disease that kills more than 40,000 American women each year.

Researchers led by Vincent Tuohy, an immunologist at the Clinic’s Lerner Research Institute, have found that a single vaccination with the antigen alpha-lactalbumin prevents breast cancer tumors from forming in mice and inhibits the growth of existing tumors.

Enrollment in human trials could begin next year. If successful, the vaccine would be the first to prevent breast cancer and could point the way to vaccines for other cancers. It also could be a huge commercial success for the Clinic, which typically licenses or spins off its discoveries to companies that take them to market.

“We believe that this vaccine will someday be used to prevent breast cancer in adult women in the same way that vaccines have prevented many childhood diseases,” said Tuohy, the study’s principal investigator, in a press release. “If it works in humans the way it works in mice, this will be monumental. We could eliminate breast cancer.”

Tuohy’s research will be published online today at Nature.com and in the June 10 issue of the Nature Medicine journal.

In Tuohy’s study, cancer-prone mice were vaccinated — half with a vaccine containing alpha-lactalbumin and half with a vaccine that did not contain the antigen. Not one of the mice vaccinated with alpha-lactalbumin developed breast cancer, while all of the other mice did.

The Food and Drug Administration has approved cancer-preventing vaccines for cervical and liver cancers — both act on viruses that cause the cancers, not on cancer formation.

Vincent K. Tuohy

In developing his vaccine, Tuohy solved the quandary of targeting cancer — an overdevelopment of the body’s own cells — rather than a foreign substance, such as a virus. Vaccinating against a virus destroys the virus, but vaccinating against a person’s own cells destroys healthy cells.

So Tuohy and his colleagues created a vaccine that seeks alpha-lactalbumin, which is a protein found in the majority of breast cancers, but is not found in healthy women except when they breast-feed. The vaccine would destroy healthy breast tissue of women who are lactating, so these women likely would not get the vaccine.

Because the protein is linked to lactation, the strategy behind the new vaccine would be to vaccinate women who are over 40 years old — when the risk of breast cancer begins to rise and pregnancy becomes less likely. Younger women at heightened risk for breast cancer could consider the vaccine as an alternative to prophylactic mastectomy.

“Most attempts at cancer vaccines have targeted viruses or cancers that have already developed,” said Dr. Joseph Crowe, director of the Clinic’s Breast Center, in the release. “Dr. Tuohy is not a breast cancer researcher, he’s an immunologist, so his approach is completely different — attacking the tumor before it can develop. It’s a simple concept, yet one that has not been explored until now.”

A year ago, Tuohy, who studies autoimmune diseases such as multiple sclerosis, was surprised when the National Institutes of Health backed development of his breast cancer vaccine after his first request. Usually, it takes several requests to land grants in the neighborhood of $1.3 million.

Several clinical trials are underway for breast cancer vaccines. The University of Arkansas is working on a therapeutic vaccine that tricks the body into producing cancer-fighting antigens, while Generex Biotechnology has had successful early phase trials with breast cancer patients on its therapeutic vaccine.

But few if any researchers appear to be going for a prophylactic vaccine — one that prevents cancer. Tuohy envisions an adult vaccination program like those that vaccinate children against diseases like polio and measles.

Global biotech firms seek partnerships in India for bigger gains


Pharma R&DThe global biotechnology industry is moving towards strategic partnerships in a bid to create faster and cost-efficient means of drug discovery. The Indian advantage — demonstrated through high-quality scientific talent pool, lower operational costs, development speed and access to a large market — is drawing big firms to rapidly externalise their R&D.

Five years ago, big biotechnology firm collaborations in India were restricted to fee for service models and it is now evolving to those based on co-development. Take for instance, Bristol-Myers Squibb’s collaboration with Biocon, which has helped it to considerably reduce the time involved in delivering active pharmaceutical ingredients.

“Partnerships now range from discovery to early clinical development, which have significant upsides even for the partnering firms,” Dr CSN Murthy, Aurigene Discovery Technologies CEO, said on the second day of industry event Bangalore India Bio 2010.

Drugmaker AstraZeneca is another case. AstraZeneca is currently altering its R&D strategy by slimming down operations in the US and Europe and reinvesting it in Asia across India, China and Japan. “We have elevated our expectations on the externalisation of R&D to 40% of our products from 25%,” said Jit Patel, director-strategic planning, business & development at AstraZeneca R&D, USA.

It recently partnered with Ahmedabad-based Torrent Pharmaceuticals to market branded generics and has signed a research collaboration with Jubilant Biosys in 2009. Jubilant Biosys operates through a hybrid model of a contract research firm and a pure-play biotech.

“We wanted to create a scale of innovation and not one of capacity,” said Sri Mosur, CEO and president, global discovery & development of Jubilant Biosys. This shared-risk model allows it to impact the product pipeline of a drug discovery major and also imbibe skills related to disease biology as the Indian talent pool, so far has been largely proficient only in chemistry.

“The Indian advantage exists even at the innovation level. But Indian companies need to identify the problems that big firms face and effectively sell themselves as solution providers for the same,” Mr Mosur added.

Success for MediWound Phase III burn care trial


MediwoundIsrael’s MediWound yesterday reported a successful Phase III clinical trial of its lead product¸ Debrase gel dressing for the treatment of second and third degree burns.

The trial included 175 patients at 25 medical centers around the world. The patients were divided into two groups, one which received Debrase, and the control group which received standard treatment.

The final analysis of the trial found statistically significant success in the trial’s two primary endpoints. Debrase reduced the number of patients who required surgery to remove burned tissue. In addition, the number of patients who required skin transplant surgery over the burned area was also reduced.

MediWound also reported statistically significant success in the trial’s secondary endpoints. These included shorter treatment time to heal the burned tissue, and reduction in blood loss involved in removal of the burned tissue without disturbance to the closing of the burned area, compared with current treatments.

On the basis of the trial results, MediWound, a Clal Biotechnology Industries portfolio company, intends to submit a marketing application for Debrase with the European Medicines Agency (EMEA) later this year. The company estimates that approval will take about a year.

Lilly CEO: Continued Deal Interest


Eli Lilly CEO John C. Lechleiter

Eli Lilly CEO John Lechleiter  hasn’t budged from his vow not to pursue a megamerger, as many of the pharma’s rivals have done. “We are not interested in a large-deal combination,” the exec said at the Sanford C. Bernstein investor conference.

Lilly (NYSE: LLY) has some tough years ahead, particularly between 2012 and 2014, when several of its major drugs go off-patent. But Lechleiter is committed to avoiding a big buyout and will rely instead on his company’s pipeline to see it through the challenge.

Even though megamergers are off the table, Lilly is seeing an increased number of deals. Lechleiter noted that it can be difficult to decide on an avenue to pursue. While diversity is essential, Lilly will look to expansion in areas congruent with its animal- and human-health model, which includes companion diagnostics and drug delivery technology.

“I think any diversification would have to be in an adjacent space,” Lechleiter said. Additionally, the pharma will continue its biotech makeover; currently, 40 percent of Lilly’s pipeline is made up of biologics, and the CEO sees a greater portion of its development efforts focused on biotech in the future.

New $1B Biotech Center in East Cambridge,Massachusetts


Binney Street Project.Alexandria Real Estate Equities, Inc. (NYSE: ARE), Landlord of Choice to the Life Science Industry®, today announced that the Cambridge Planning Board has granted final zoning approval for its transformative life science development, known as the Binney Street Project.

This development, with its crucial adjacency location near Kendall Square, in the heart of East Cambridge, is positioned to be the epicenter of Cambridge’s life science industry.

The Binney Street Project is an 11.3-acre development that will consist of approximately 1.72 million square feet of office/laboratory space and other mixed uses.  It will include a mixed mode transportation center and more than two acres of public open space for the East Cambridge community.  Once completed, the Project will have five highly sustainable state-of-the-art life science facilities in addition to the preservation of existing historic buildings.  All buildings will be LEED certifiable, employing state-of-the-art design and technology featuring sustainable operations including high-efficiency mechanical systems, rooftop storm water management and water-efficient landscaping.  This innovative development, in the heart of the renowned Kendall Square district, will provide convenient access to leading research and academic institutions including Massachusetts Institute of Technology, Whitehead Institute for Biomedical Research, the Broad Institute and Harvard University.

“The Binney Street Project is one of the most important developments of its kind and will further enhance Cambridge’s position as a world leading center for life science research and development,” said Tom Andrews, Senior Vice President and Regional Market Director, Alexandria Real Estate Equities, Inc.  “We have worked closely with the City of Cambridge on this project and look forward to moving forward with the development of a truly unique, world-class life science cluster that will attract leading research organizations, pharmaceutical and emerging biopharmaceutical companies to an already vibrant broad and diverse life science community.”

Alexandria Real Estate Equities, Inc. has a dominant presence in the Cambridge market, with more than 2.1 million square feet of office/laboratory space and more than 60 client-tenants.  Alexandria’s Technology Square life science cluster is one of the world’s leading destinations for the industry.  Within the Cambridge market, Alexandria includes among its client tenants such industry leaders as GlaxoSmithKline, Inc., Massachusetts Institute of Technology, Novartis AG, Pfizer Inc., Biogen Idec, Dyax Corp., Alnylam Pharmaceuticals, Inc. and Thermo Fisher Scientific Inc.

Ascenta Therapeutics Licenses Cancer Drug Candidates to sanofi-aventis ; $398 M deal


A Global License and Research Collaboration Agreement on compounds designed to restore the p53 tumor suppressor function in cancer cells
Ascenta TherapeuticsAscenta Therapeutics announced today the signing of a global collaboration and licensing agreement with sanofi-aventis (EURONEXT: SAN and NYSE: SNY) covering several early-stage agents being investigated for their potential to restore tumor cell apoptosis (programmed cell death).  These orally-active, small-molecule drug candidates inhibit the interaction between HDM2 (Human Double Minute 2) and p53, removing a block to normal p53 tumor suppressor function and potentially enhancing cancer control and treatment.

Under the terms of the agreement, Ascenta Therapeutics has given sanofi-aventis an exclusive worldwide license to develop, manufacture, and commercialize all compounds issued from this program. In return, Ascenta will receive an upfront payment, as well as development, regulatory and commercial milestone payments that could reach a total of $398 million. In addition, Ascenta is eligible to receive tiered royalties on worldwide product sales.

The agreement includes two agents that Ascenta Therapeutics previously in-licensed from the University of Michigan, MI-773 and MI-519-64, which should soon enter preclinical development.  Both Ascenta Therapeutics and sanofi-aventis will continue to fund research on these targets at the University of Michigan, and Ascenta Therapeutics may participate in ongoing research activities and potential future clinical development.

“Ascenta’s mission since its founding has been to discover and develop novel small molecules that can trigger apoptosis in cancer cells. Sanofi-aventis has a great record of bringing innovative cancer therapies like these to cancer patients around the world,” said Mel Sorensen, M.D., President and Chief Executive Officer of Ascenta Therapeutics. “Restoring tumor suppressor function through the inhibition of the HDM2-p53 interaction offers the potential to control and prevent cancer progression. We are delighted to have sanofi-aventis join us and the University of Michigan in this endeavor to turn exciting science into novel cancer medicines.”

About HDM2/p53 Inhibition

Inhibiting the interaction between p53 and HDM2 (human double minute 2, and its murine counterpart, MDM2) is a very promising approach to restoring the natural tumor suppression function of the p53 protein.  The p53 tumor suppressor is a principal mediator of growth arrest, senescence, and apoptosis in response to cellular damage. It is called the “guardian of the genome” because of its role in controlling the cell cycle and monitoring the integrity of the genome. HDM2 is the principal cellular antagonist of p53, acting to limit the p53 growth-suppressive function. Loss of p53 function is involved in 50 percent of cancers, either through mutation, overexpression or amplification of HDM2 in wild-type p53 tumors.

Johnson & Johnson Highlights Growth Strategies for its World-Leading Medical Devices & Diagnostics Segment


New products and acquisitions enhance market leadership positions and build inroads to new opportunities

Robust pipelines continue delivering new breakthroughs and treatments for patients

Expansion of product reach and medical training institutes drives further growth in emerging markets

Alex Gorsky, worldwide chairman of Johnson & Johnson’s Medical Devices & Diagnostics segment.

Johnson & Johnson (NYSE: JNJ) will be reviewing the growth strategies for its Medical Devices & Diagnostics (MD&D) segment at a meeting with the investment community today.  Senior leaders will be highlighting the new products, robust pipelines, expanding geographic presence, and other strategies that will sustain the long-term growth of the company’s largest business segment in a $350 billion, worldwide medical device and diagnostics market.

“Thanks to the hard work of thousands of talented associates, we are the largest and strongest medical device company in the world today, and poised to continue advancing patient care in the future,” said Alex Gorsky, worldwide chairman of Johnson & Johnson’s Medical Devices & Diagnostics segment.

The company’s MD&D business segment, which generated $23.6 billion in sales in 2009 and became Johnson & Johnson’s largest business segment, holds the No. 1 or 2 market positions in the majority of its markets.  It includes seven global franchises:

  • Cordis: a leader in the treatment of cardiovascular disease;
  • DePuy: a leader in orthopaedics, spinal care, sports medicine and neurosurgical devices;
  • Diabetes Care: a leader in products that allow people with diabetes to monitor and control their blood glucose levels;
  • Ethicon: a leader in sutures, tissue repair and reinforcement products, women’s health, aesthetics and conditions of the ear, nose and throat;
  • Ethicon Endo-Surgery: a leader in surgical device solutions for minimally invasive and open surgery; and Advanced Sterilization Products, a leading developer of solutions for the reduction of healthcare-associated infections;
  • Ortho Clinical Diagnostics: a leader in medical diagnostic products;
  • Vision Care: a leader in the global contact lens market.

“Our MD&D businesses compete in a number of large, well-established and under-penetrated markets like joint replacement, contact lenses and sutures — markets where we can grow through the introduction of more advanced products and continued geographic expansion,” said Gorsky.  “At the same time, we are expanding into other high-growth markets such as biosurgicals, energy, electrophysiology and other surgical specialties.  We are using our own pipeline, as well as licensing agreements and select acquisitions, to bring us new capabilities.”

Launching New Products

Today’s presentations will highlight a number of products that have either launched this year or are continuing their global roll-outs in 2010.

Ethicon Endo-Surgery, for example, continues to introduce new energy instruments as part of its HARMONIC® family of technology that delivers precise ultrasonic energy to minimize thermal tissue damage to the patient, while providing surgical efficiency.  Diabetes Care is rolling out a new blood glucose monitoring system, OneTouch® Verio TM that provides the next generation of accuracy and precision, the number one need for diabetes patients.

Meanwhile, Vision Care continues rolling out its 1-DAY ACUVUE® TruEyeTM Brand Contact Lenses, the world’s first daily disposable silicone hydrogel lens on the market, which is currently available in Europe and Japan and is expected to launch in the U.S. later this year.

In addition, Ethicon continues to focus on patient comfort and surgeon ease-of-use as it builds its portfolio of hernia repair products with ETHICON PHYSIOMESHTM Flexible Composite Mesh and  its first entry into the hernia mesh fixation market with ETHICON SECURESTRAPTM 5mm Strap Fixation Device.  Ortho Clinical Diagnostics also continues to expand the adoption of its VITROS® 5600/3600 diagnostic systems launched last year, while increasing the number of tests available on them.

Advancing Pipelines

Johnson & Johnson’s MD&D segment has received more than a dozen regulatory approvals so far in 2010, and it plans to make approximately 80 significant submissions across its seven franchises between 2010 and 2012.

Cordis’ NEVOTM Sirolimus-eluting Coronary Stent, featuring unique reservoir-based technology to treat cardiovascular disease, filed for CE Mark approval earlier this year and presented positive one-year clinical trial data at EuroPCR last week.  DePuy is awaiting FDA approval in the U.S. for the PINNACLE® CoMpleteTM Acetabular Hip System.  This first ceramic-on-metal hip bearing to be considered for approval by the FDA combines the durability and stability of metal with the enhanced wear characteristics of ceramic. And, Ethicon plans to make a BLA filing in the U.S. for its Fibrin Pad in the fourth quarter; this hemostasis product combines two biomaterials and two biologics to stop bleeding during surgical procedures.  The Vision Care franchise has also completed clinical trials for a contacts lens that delivers anti-allergy medication on a lens, and is planned to be submitted to the FDA later this year.

Meanwhile, the MD&D segment continues to make strategic acquisitions to strengthen its core portfolios and expand into adjacent markets.  Acclarent, Finsbury Orthopaedics and Gloster Europe are acquisitions that provide breakthrough surgical products to move into ear, nose and throat procedures; expand its orthopaedics portfolio; and increase its portfolio of infection prevention technologies.

Expanding Global Presence

As the MD&D segment expands in emerging markets, they continue globalizing their current portfolios; developing more localized, market-appropriate products; and leveraging their medical training institutes for educating medical personnel about the latest surgical techniques and treatments.

For example, the 1-DAY ACUVUE® DEFINETM NATURAL SHINETM contact lens builds on the recent success of other beauty-enhancing DEFINE lenses in Asia.  And, SYNSYLTM is a synthetic absorbable suture created specifically for China to compete with locally manufactured silk sutures that don’t offer the same level of performance.

Meanwhile, the MD&D segment continues to expand its global manufacturing and training footprint to support emerging market growth.  DePuy continues to increase capacity at its state-of-the-art manufacturing facility in Suzhou, China, and MD&D’s most recent medical training center opened in Sao Paulo, Brazil, earlier this year and expects to train 4,000 doctors and nurses in the region each year.

Brief summaries of the franchises, new products and pipelines being discussed in today’s presentations are available in an MD&D Franchise Backgrounder.

Investors and other interested parties may access the meeting by visiting the Investor Relations section of the Johnson & Johnson website at www.investor.jnj.com for a simultaneous webcast of the presentation.  Full copies of the presentations as well as a replay and podcast will be available approximately two hours after the live webcast concludes.

SOURCE Johnson & Johnson

Xenical and Alli Liver Damage Reports Reviewed by FDA


The FDA appears to be reviewing a possible connection between reports of liver damage and orlistat, which is a weight-loss drug contained in the prescription Xenical and the over-the-counter Alli. 200259-Mat6

According to a report by Scrips News, the FDA discussed orlistat’s potential link to hepatoxicity at an April 16 meeting of its Drug Safety Oversight Board (DSB), and the agency is continuing to review whether there is any connection between the drug and reports of liver damage.

The FDA is looking at both the prescription and non-prescription versions of the drug and said that any action taken would depend on the outcome of its analysis. The FDA would not state how many post-marketing liver damage reports it was investigating.

Orlistat is the active pharmaceutical ingredient in Roche’s Xenical, which was approved as a prescription medication in 1999. Last year, GlaxoSmithKline’s Alli, a lower dose version of the drug, was approved for over-the-counter use.

The medications are intended for use together with a reduced-calorie diet, and work by preventing the absorption of fats, thereby reducing caloric intake.

In 2008, Xenical generated sales of $30 million and Alli generated sales of $131 million during its first full year on the market. Hepatoxicity is chemical damage to the liver, usually caused by drugs. The liver is the body’s main mechanism for metabolizing drugs, making it susceptible to chemical damage.

Hepatoxicity can manifest in a variety of ways, including:

  • Necrosis of the liver, a form of hepatitis
  • Inflammation of the liver
  • Vascular lesions
  • Acute liver failure

Xenical’s labeling already lists liver injury as a potential side effect, stating that “exceptional cases of hepatitis that may be serious have been reported.” However, the label points out that that no direct relationship has been established between hepatitis and orlistat therapy.

Obesity itself is often linked to liver injury, and the fact that the FDA is reviewing adverse event reports associated with the use of Xenical and Alli does not mean that there is any cause and effect relationship.

The primary known side effects of Xenical and Alli include oily and loose stools, fecal incontinence, frequent or urgent bowel movements and flatulence, which tend to be most severe when the treatment is started and may decrease with time.

The FDA put orlistat on a list of drugs linked to new safety risks earlier this year after examining reports of Xenical’s possible links to rectal bleeding, however the agency determined that no action was needed.

Transformation for a New Takeda: 2010-2012 Mid-Range Plan


OSAKA, Japan, May 12, 2010 – Takeda Pharmaceutical Company Limited (Takeda) today announced the start of its 2010-2012 Mid-Range Plan to transform the Company into a new Takeda.

Under its 2006-2010 Mid-Range Plan, Takeda had made progress towards becoming a world-class pharmaceutical company. The Company achieved this by strengthening its oncology pipelines with the acquisition of Millennium Pharmaceuticals, unifying its U.S. sales network through the division of TAP 1) and its subsequent integration with TPNA 2), and enhancing its global governance structure with the establishment of position of leading International Operations and also the ones as Chief Scientific Officer and Chief Administrative Officer.

However, the business environment for the pharmaceutical industry is changing dramatically, with the pharmaceutical industry as a whole facing barriers to technological innovation that have halted progress in breakthrough novels drugs, stricter approval processes for new drugs in advanced nations, and radical upheaval in healthcare systems. Takeda has also experienced halted development in some pipelines and delays in obtaining drug approvals. The Company has therefore decided to respond flexibly to these changes in the business environment and ensure a sustained growth trajectory by developing and implementing a Mid-Range Plan starting in the fiscal 2010, one year ahead of schedule.

Takeda positions the period covered by the 2010-2012 Mid-Range Plan as a time of transformation, in which the Company will move forward from its past successes and grow into a new Takeda, setting a course for further development. To achieve the goals of this Mid-Range Plan, the Company has decided on a new management policy referred to as the Vision, which focuses on Company activities on the themes of Innovation, Growth, and Culture. These are the key concepts in the transformation that Takeda will engage in ensuring sustained growth in the medium- to long-term.

During its nearly 230-year history, Takeda has often encountered difficulties, which it has overcome to achieve growth by implementing its corporate philosophy of “Takeda-ism = Integrity, meaning fairness, honesty and perseverance.” Takeda has committed itself to the complete execution of the new Mid-Range Plan, drawing on the combined knowledge and abilities of every employee in the Takeda Group and guided by thorough compliance on a global scale. In this way, the Company will work to realize its corporate mission of “striving towards better health for patients worldwide through leading innovation in medicine.”

1) TAP : TAP Pharmaceutical Products Inc.
2) TPNA : Takeda Pharmaceuticals North America, Inc.

Financial targets for fiscal 2012
Net sales : 1,330 billion yen
Research and Development expenses : 300 billion yen
Operating income : 290 billion yen
Net income : 200 billion yen
Earnings per share (EPS) : 253 yen
EPS : 294 yen

(excluding extraordinary income/loss, extraordinary factors arising from business acquisitions and similar events)

(Note 1)
The financial targets for fiscal 2012 are calculated on the assumption that the entry of generic versions of Actos products in the U.S. will start in August 2012.

(Note 2)
EPS (excluding extraordinary income/loss, extraordinary factors arising from business acquisitions and similar events) is calculated as:
Net income for the year less: (1) extraordinary income/loss; and (2) amortization of goodwill and intangible assets arising in connection with business acquisitions and similar events; divided by the average number of outstanding shares issued during the year.

1. Vision
Takeda’s vision is to embody global pharmaceutical leadership through innovation, growth, and culture, guided by an unwavering commitment to significantly improve the lives of patients.

  • Innovation based on bold leadership in science and medicine resulting in the discovery, development and delivery of high-quality, differentiated products focused on patient needs.
  • Sustainable growth in corporate value by leveraging core therapeutic areas, and an industry-leading pipeline and product portfolio.
  • A culture based on good corporate citizenship that empowers employees through collaboration, inclusion, trust and timely decision making.

2. Strategies for Implementing the Vision

  • Innovation

Ensure to launch products in the late-stage development
Takeda ensures to bring new products to market from the fiscal 2010 onwards through steadily conducting clinical study of the products in the late-stage development. In addition, the Company aims to build a pipeline that is balanced across therapeutic areas, each stage of development and geographical regions through creating new drugs from its own R&D as well as actively pursuing M&A and licensing activities.

Concentrate resources into core therapeutic areas
Takeda will concentrate investment of its management resources into new core therapeutic areas of “Metabolic & CV” (obesity, diabetes and atherosclerosis), “Oncology”, and “Central Nervous System Diseases” (depression, schizophrenia, and Alzheimer’s disease). In therapeutic areas where patient satisfaction with treatment is already high, Takeda will focus on the prevention of such diseases. In areas where medical needs remain largely unmet, Takeda will create drugs that are capable of bringing fundamental cure, in addition to drugs for symptomatic treatments.

  • Improve R&D productivity

Takeda will increase the probability of success in clinical studies by rigorously selecting new drug candidates at the early development stage to select those with differentiable profiles for further development. Moreover, the Company will utilize its global framework centered around its new research center to further enhance alliances across regions and departments, while also making active use of external resources, to create new high quality drugs to satisfy unmet needs among patients.

  • Growth

Launch new drugs and maximize early their values
In Japan, Takeda will maintain its position as Japan’s number one pharmaceutical company (by market share) by achieving early penetration and sales expansion of a host of new products and by strengthening its cancer and central nervous system disease franchises. In the United States and Europe, Takeda will quickly diffuse new products into the market. At the same time, in line with the future product mix in these regions, the Company will establish a flexible sales and personnel structure to cover not only the primary care field but also specialized fields.

Further expand into new regions
While continuing efforts to expand Takeda’s presence in the large-scale markets of U.S. and Europe, the Company will also accelerate expansion into emerging markets, and other countries and regions where high market growth is expected in order to realize a globally balanced regional portfolio in terms of sales and profits. The goal is to cover about 90% of the global market by fiscal 2012.

  • Culture

As part of the transformation into a new Takeda, the Company will create an open and active corporate culture. To achieve this, the Company will foster a working atmosphere in which all Takeda Group employees can achieve their full potential, working with colleagues of different nationalities, cultures, genders and careers. At the same time, Takeda will step up its training programs to develop staff with a global perspective.

3. Active execution of strategic investment

Takeda will make strategic investments actively and flexibly, having strictly evaluated the effect of a proposed investment. The Company will pursue all opportunities, including M&A, product acquisition, and introduction of pipelines.

4. Dividend Policy
For the dividend policy during this Mid-Range Plan, Takeda plans to maintain a stable dividend and has adopted a basic policy of maintaining dividends per share at the fiscal 2009 level.

Mesoblast Limited (ASX:MSB) To Acquire Angioblast Systems Inc, Successfully Completes Capital Raise


Australia’s regenerative medicine company, Mesoblast Limited (ASX:MSB) (OTC:MBLTY) today announced that it will acquire its United States associate company, Angioblast Systems, Inc. (Angioblast). Additionally, Mesoblast announced it has completed a capital raising of A$37 million to fund the acquisition and advance operations of the expanded Mesoblast Group. These funds comprise A$24 million invested immediately and A$13 million committed subject to both shareholder approval and completion of the acquisition offer.

Mesoblast Chairman Brian Jamieson said: “We are delighted to bring the commercial rights to the patented adult stem cell technology platform under one umbrella. With Mesoblast moving to 100% ownership of Angioblast, Mesoblast shareholders will derive much greater potential benefit from product commercialisation, and from the broader strategic partnerships or collaborations Mesoblast will now be able to conclude.”

The capital was raised from United Kingdom institutional and sophisticated investors, as well as from new and existing Australian investors, at a share price of A$1.70, representing a 12% discount to the Company’s closing price on May 3 2010.

The acquisition has been structured on an agreed exchange ratio of Mesoblast shares for Angioblast stock. To Osteoarthritis_acquire the remaining fully-diluted Angioblast stock which is not already owned by Mesoblast (approximately 67%), the Company proposes to issue an additional 94.6 million Mesoblast shares to Angioblast security holders. Together with Mesoblast’s current 140.6 million shares on issue, post-acquisition the Mesoblast Group will have a total of up to 235.2 million shares outstanding.

Angioblast stockholders will be given the election to take the acquisition consideration either as 100% Mesoblast fully paid ordinary shares or up to 15% in cash and the balance (a minimum of 85%) in Mesoblast fully paid ordinary shares. The cash component will enable Angioblast stockholders who are subject to United States federal tax to fund the payment of capital gains tax arising as a result of this transaction.

The acquisition is subject to various conditions including Mesoblast and Angioblast shareholder approvals and satisfactory due diligence. An Extraordinary General Meeting of Mesoblast shareholders to ratify the acquisition is expected to be held before the end of June 2010, with all shareholders receiving full documentation prior to this date.

At the Mesoblast share price as at the close of trading on May 3 2010, this would result in a capitalisation of Mesoblast (not including the capital raising as referred to in this announcement) of A$455 million.

Mr Jamieson also announced the appointment of Mesoblast’s current Executive Director, Professor Silviu Itescu, as Chief Executive Officer and Managing Director of the Group, Mesoblast Limited. The appointment takes effect immediately.

“The appointment of Professor Itescu as the leader of the Group will ensure that Mesoblast continues to deliver on shareholder value.

“As a leader in the global stem cell space, he brings enormous international knowledge of the regenerative medicine industry, combined with experienced and formidable business acumen,” Mr Jamieson said.

Professor Itescu said that the Angioblast acquisition would enable the Mesoblast Group to significantly broaden its product portfolio based on 100% ownership of the intellectual property underpinning the company’s patented adult stem cell technology platform.

Transforming Mesoblast from a biologics company focused on orthopaedic applications to a global leader in the broader regenerative medicine industry should prove to be a pivotal event in the Company’s evolution,” he said.

“By consolidating our technology platform and assets into one company we will be able to both streamline our corporate operations and strengthen the global leadership team as the Company moves to the next level of its corporate maturity. Additionally, we will now be able to rationally deploy all of our available resources according to where we deem to have the greatest commercial opportunities.

“Mesoblast is now a mature multi-product company with products in late, mid, and early stage development. The Company’s product pipeline will be significantly extended beyond its orthopaedic focus, including spinal fusion and osteoarthritis, to include products for treating diverse conditions such as congestive heart failure, heart attacks, eye diseases, diabetes, and bone marrow repair.

“This breadth of products will enable the Mesoblast Group to focus on three simultaneous commercial strategies: taking lead products to market on our own and retaining 100% of the commercial upside, entering into distribution agreements to leverage sales/marketing strength, and partnering through broad-based strategic alliances,” Professor Itescu added.

Test may let transplant patients skip biopsies


By Julie Steenhuysen

A gene-based blood test worked as well as a surgical procedure used to check for signs of rejection in patients with heart transplants, U.S. researchers said on Thursday.

They said the simple blood test called AlloMap, made by molecular diagnostics company XDx Inc, will allow heart transplant patients to forego frequent biopsies of the heart, a procedure dreaded by many transplant patients because it is uncomfortable and can damage heart valves in a few patients.

“This represents a major step forward in the way we manage a patient after heart transplants because we can now safely reduce the numbers of heart biopsies,” said Dr. Hannah Valantine of Stanford University, who designed the study to determine whether it was safe to reduce the number of necessary biopsies by using the blood test.

Valantine and colleagues presented the findings at the International Society for Heart & Lung Transplantation annual meeting in Chicago.

Heart transplant patients need to be monitored regularly for signs of organ rejection, typically through a procedure called an endomyocardial biopsy, in which doctors insert a tube into a vein in the neck and into the heart, where tiny bits of tissue are collected and tested.

Heart transplant recipients typically get 15 to 20 biopsies in the first six months after a transplant, and two to four biopsies per year after that.

“We need to monitor patients very carefully to detect a rejection so that we can treat it in a timely fashion and prevent the heart from failing,” said Valantine, whose study was published online in the New England Journal of Medicine.

She said biopsies are invasive and uncomfortable and are associated with a low risk of complications and death.

“The patients dislike them and there is a huge cost burden to institutions,” Valentine said, noting that the biopsy costs $4,000, about $1,000 more than the AlloMap test.

The study was funded by XDx, a molecular diagnostics company in Brisbane, California.

Valantine said doctors have been doing the biopsy procedure for 30 years. Her study compared that procedure to the AlloMap test, which checks the blood to see if specific genes associated with rejection are turned on or expressed.

The team compared results of 600 patients who were randomly assigned either to have a biopsy or to have an echocardiogram and the AlloMap test.

Valantine said the blood test worked as well as routine biopsies, with patients in the blood test group showing similar rates of rejection and other complications to those who got biopsies.

Researchers are also doing a cost analysis comparing the two procedures, but those results are not yet available.

The blood test is currently offered at 65 transplant centers in the United States. The U.S. Food and Drug Administration approved it for heart transplant patients in August 2008.

Stimulating Healing in the Heart


A startup aims to repair heart damage with peptides that trigger the proliferation of heart cells.
By Emily Singer

Growing heart muscle: A peptide called neuroregulin1 can stimulate heart muscle cells (red) in rats to divide. Markers of dividing cells (red) are shown in green/yellow. Cell nuclei are shown in blue. Credit: Bersell et al, Cell

While the human heart was once thought incapable of regeneration, growing evidence shows that even the adult heart can grow new cells, albeit slowly. Roger Hajjar, director of the Cardiovascular Research Center at the Mount Sinai School of Medicine, in New York, and Bernhard Kuhn, a cardiologist at Children’s Hospital Boston, aim to harness this regenerative ability to change how heart disease is treated. They cofounded a startup called CardioHeal, based in Brookline, MA, to develop peptide drugs that can spur growth of new heart muscle cells in the human body.

The scientists have identified a pair of peptides that can stimulate new cell growth and improve heart function in rodents induced to have heart attacks. Hajjar’s lab at Mt. Sinai is now testing one of the peptides, periostin, in pigs induced to have heart attacks. Because these animals have hearts similar in size to humans, they provide a good model for testing new therapies prior to human clinical trials. Preliminary results show that injecting the peptide into the pericardium, the lining around the heart, seems to help. “They’re not completely back to normal, but they’re much better,” says Hajjar.

Researchers hope the molecules will ultimately provide an alternative approach to treating heart disease. Currently, people who suffer a heart attack get medication, such as beta blockers, to make it easier for the heart to beat, and surgery to clear blocked arteries. “But none are directed at giving new heart muscle back after myocardial infarction,” says Kuhn. The cardiologist says patients regularly ask him if the treatment is available for them, part of the reason he decided to found the company. “I’ve been getting patient requests for a couple of years, but we don’t have an open trial or anticipate opening one anytime soon.”

Cardioheal’s approach is, to some degree, in competition with stem-cell therapy, which is already being tested in humans. Scientists are working on different ways of harvesting and delivering stem cells to patients with heart disease, and clinical trials have so far yielded mixed results. Transplanted cells appear to have difficulty surviving and integrating into their new environment. In fact, some scientists suggests that benefit of cell transplants comes from the cells ability to stimulate innate growth. Triggering this process with peptides “may be a simpler method of treatment of certain conditions such as cardiomyopathy [an enlarged heart] where the problem is lack of viable, contractile heart muscle cells,” says Amish Raval, a cardiologist at the University of Wisconsin, in Madison, who is not involved with the company.

Cardioheal still has a number of questions to address before testing the peptides in patients. “What is the least invasive way of getting it to the patient’s heart?” asks Hajjar. “At what point after heart attack would you deliver this–early, late, when a patient develops congestive heart failure?” Researchers say they haven’t seen adverse effects in treated animals, but extensive safety testing needs to be done before human trials. “Tumor formation, noncardiac muscle tissue formation, causing dangerous arrhythmias needs to be systematically evaluated in animal models with broad dose ranges tested,” says Ravel. “I would be interested in knowing whether the cardiac cells actually integrate with the environment in the heart, or just independently contract. There has to be electrical and mechanical integration for this treatment to work.”

Copyright Technology Review 2010.

New drug aims to "switch off" rheumatoid arthritis


UK scientists are hopeful of developing a completely new approach that may “switch off” rheumatoid arthritis (RA).

Following encouraging results from a pilot study in a handful of patients with RA, a team of researchers funded by medical research charity Arthritis Research UK and pharmaceutical company GlaxoSmithKline will set up a small phase I multi-centre trial of a targeted T-cell anti-CD3 monoclonal antibody therapy called otelixizumab, in the next four to six weeks.

John Isaacs, Professor of Clinical Rheumatology at Newcastle University's Musculoskeletal Research Group

John Isaacs, Professor of Clinical Rheumatology at Newcastle University’s Musculoskeletal Research Group

Lead researcher Professor John Isaacs, Professor of Clinical Rheumatology at Newcastle University’s Musculoskeletal Research Group, said that if the drug was shown to be effective and safe in subsequent Phase II and III trials, it could be available for patients with rheumatoid arthritis in eight to ten years. It is currently in Phase III trials for autoimmune type 1 diabetes mellitus.

Researchers hope that otelixizumab will be as effective in reducing symptoms as the current “gold standard” therapy for severe rheumatoid arthritis, anti-TNF therapy, but will have a more sustained effect from just a one-off one course of treatment.

“Everything we know about this drug suggests that it has the potential to be a powerful treatment, but safety is paramount, and this is what we aim to demonstrate in this study,” he added.

Forty patients from around the UK who have failed to respond to conventional drug treatment will receive otelixizumab or placebo intravenously over a five day period as part of the trial.

“There is preliminary preclinical and clinical data to believe that doses lower than those used in the pilot study may have clinical benefit with a more favorable safety and tolerability profile. Patients in the current trial will receive a much lower dose than we used previously. The first group of ten patients will receive the lowest dose, and if this dose proves to be safe, then the dose will also increase slightly for the next ten, and so on,” explained Professor Isaacs.

“We aim to etermine a dose which is safe but which also appears to improve symptoms. We anticipate that the dose we identify in this manner will subsequently be studied in larger Phase II and III studies, specifically designed to demonstrate a beneficial effect on symptoms.”

In an important aspect of the study, researchers from Newcastle University and King’s College London, will also be performing laboratory studies aimed at identifying and analysing potential biomarkers in the blood that might predict whether or not a patient will have a sustained response to the therapy.

Rheumatoid arthritis, which affects around 380,000 people in the UK, is caused when the body’s immune system attacks itself, causing inflammation, pain and stiffness in the joints. Other internal organs can also be affected.

CD3 is a molecule found on the surface of T-cells (white blood cells that control the body’s immune response), and is important in stimulating the T-cells into action. Otelixuzumab, an anti-CD3 monoclonal antibody, works in two ways by latching onto T-cells, potentially switching them off and increasing regulatory cells that control inflammation .

If found to be both safe and effective, otelixizumab could rival anti-TNF therapy, which has to be administered to patients on an ongoing basis. Anti-TNF therapy, also pioneered and developed by Arthritis Research UK scientists, has revolutionised treatment of the condition for the past decade, if otelixizumab could give the same longterm benefit with only a short course of treatment, it would offer a real advantage.

The charity is funding the study with an experimental medicine grant of more than £450,000, with a further £1.7m from GlaxoSmithKline.

Professor Alan Silman, medical director of Arthritis Research UK, said that although the research was at a very early stage, the potential prize – a new and highly effective one-off treatment for rheumatoid arthritis – was very great.

Researchers see cancer vaccine revolution on the horizon


illustration canceer vaccine

Killer T cells (in blue) attach to a cancer cell, releasing enzymes that disintegrate its outer covering. © Jim Dowdalls/Photo Researchers, Inc.

One of the persistent frustrations in cancer treatment has been the way that tumors can evade our immune systems as they grow and multiply inside our bodies.

Even though cancer cells have special surface markers, known as antigens, the body often doesn’t seem to be able to mount a full-fledged attack against the tumors, and the longer they last, the more they seem to suppress the immune response.

Yet it doesn’t have to be that way, says a dedicated band of scientists in universities and companies around the globe. In fact, they say, we may be on the verge of being able to vaccinate people against cancer in the same way we do with infectious diseases.

“I think we really are on the cusp of a revolution in cancer immunology,” said Andres Salazar, CEO of Oncovir, a Washington, D.C., company that makes an immune system booster for cancer vaccines. “We hope to make patients allergic to their cancers.”

The first commercial cancer vaccine out of the gate is likely to be sipuleucel-T, a vaccine against advanced prostate cancer being made by Dendreon Corp. of Seattle, Wash.

Not far behind in the pipeline is Stimuvax, a vaccine being made by Merck in Germany that targets a cancer marker known as MUC1, which is present in many different tumors.

That is the same target that UPMC researcher Olivera Finn has developed her own vaccine against.

Dr. Finn’s vaccine, which has been in development for several years, has already shown limited success in advanced pancreatic cancer patients.

But because she believes these vaccines will work best in people who do not yet have cancer, she and UPMC researcher Robert Schoen are testing the vaccine now in patients who have precancerous polyps in their colons, to see if it prevents the onset of colorectal cancer.

While she is still a couple years away from being able to report results, Dr. Finn knows the vaccine has created a strong immune response in the patients and has had few side effects.

The hope? “If we immunize early on, the cells that become abnormal might actually be eliminated by a strong immune response,” she said.

James Gulley, a leading vaccine researcher at the National Cancer Institute, agrees with that approach. He said there is growing evidence that the immune system doesn’t work as well against cancers that are more advanced, which “leads me to believe the best time to try vaccines thus might be before the tumor gets too large.”

That is also the goal of a new cancer vaccine trial being started here for patients with gliomas, a type of brain cancer.

That experiment, being run by UPMC neurosurgeon Hideho Okada, will administer the first vaccine ever developed for low-grade gliomas, which includes an immune system booster called Hiltonol.

These cancers are especially insidious, Dr. Okada said, because they often grow slowly for several years and the patients look and feel healthy. Then suddenly, they convert into an aggressive form of brain cancer that kills the patients.

“A low-grade tumor is not a benign tumor,” he said. “Unfortunately, a diagnosis with a low-grade glioma today is still a death sentence” — something he hopes the new vaccine can reverse.

The trial will be small to start with, involving 18 patients with new cancers and nine with recurrent tumors.

“We believe that immunotherapy could be long-lasting,” Dr. Okada said. “The actual drug doesn’t have to be present in the system, unlike chemotherapy, and the slow-growing nature of these gliomas gives us sufficient time to vaccinate and revaccinate patients.

“Our goal is to educate the immune system so that it recognizes the cancer-specific antigens.”

A key part of that will be the Hiltonol booster made by Dr. Salazar’s company.

The substance, named for co-inventor Hilton Levy, mimics the DNA of a virus, and seems to deliver a “warning signal” that fires up the immune system, Dr. Salazar said. It is being used now in about 12 different cancer vaccine trials, he said, including Dr. Okada’s.

Hiltonol is made of double-stranded DNA, “which doesn’t normally occur in mammalian cells,” he said, “but is a product of viral replication, so when mammalian cells see it, they say, “There’s a difference here. ”

Besides monitoring the patients who had colon polyps, Dr. Finn has also reported encouraging results with her vaccine in specially bred mice.

The mice have human genes that make them prone to get inflammatory bowel disease, which is a known risk factor for colorectal cancer. In fact, if they are left untreated, she said, about 80 percent of the mice will go on to get cancer.

When her team administered the MUC1 vaccine to the mice, though, not only did far fewer of them get inflammatory bowel disease, but almost none of them went on to get cancer.

The encouraging results of MUC1 vaccines aren’t confined to animals.

The version that is now being tested by Merck showed a 17-month survival advantage for advanced lung cancer patients who got the vaccine vs. those who didn’t in an earlier trial.

While the current testing has been suspended temporarily because one patient got encephalitis, the man whose company invented the vaccine is encouraged by the progress it has made.

Robert Kirkman, president of Oncothyreon, the Seattle, Wash., company that developed the vaccine, said he understands the logic of testing cancer vaccines on patients who aren’t as sick, but said that presents a financial challenge.

If vaccines were to be tested on a large group of patients with earlier stage cancer, it could mean following them for up to 10 years to see if the therapy was effective, and that would be enormously expensive.

If his company’s vaccine, Stimuvax, demonstrates a relative survival benefit for patients with later-stage cancers and can then be approved as a commercial product, he said, “it’s likely the work will then be done to show it works in earlier-stage disease, but it’s much easier to do that after you’ve got a revenue-generating product.”

The National Cancer Institute’s Dr. Gulley said he thinks there may be a middle ground between what is “biologically plausible and financially feasible” for testing cancer vaccines on human patients.

There is evidence that cancer vaccines take longer to show beneficial results than other kinds of therapies, he said, partly because the immune system needs time to gear up to fight the tumor.

In doing human trials of vaccines, he said, “if I were to err on one side or the other, I’d err on the side of what’s biologically plausible.” Too often in cancer treatment, “everyone’s looking for the big payoff with little effort, and that’s exactly the wrong thing to do.”

One other possible benefit of vaccines: They may make it possible for some people to live with their cancers for many years, even if the malignancies aren’t completely wiped out.

With Dr. Okada’s brain tumor patients, for instance, it would be a major advance if a vaccine could just stop their tumors from becoming aggressive and life-threatening.

Even with the addition of newer forms of chemotherapy in recent years, doctors who treat gliomas have only been able to extend average life spans by about three months over the past couple of decades.

“So if I could even make brain cancer a chronic disease like hypertension or diabetes,” he said, “I would be ecstatic.”

Washington Life Sciences Fund awards $15M


Three separate research programs in Seattle were awarded about $5 million each by Washington state’s Life Sciences Discovery Fund.

Winning grants were:

— Stephen Friend of Sage Bionetworks, of Seattle. His program focus, according to the fund, is “to more accurately and comprehensively model biological systems through their network of interactions to develop safer and more effective drugs and diagnostic tests.”

— Thomas Matula of the University of Washington. His program focus, according to the fund, is “to develop, translate and commercialize new ultrasound techniques for molecular imaging and therapy.”

— Peggy Porter of Fred Hutchinson Cancer Research Center. Her program focus, according to the fund, is “to facilitate cancer treatment through comprehensive biological collection and distribution.”

Fund officials said 19 proposals were submitted before the three winners were chosen.

Started in 2008, the fund draws $35 million a year for 10 years from a settlement with tobacco companies. It’s administered by an 11-member board of trustees. The governor appoints seven trustees, and four are appointed by legislators

Scientists use peptide to inject drugs deeper into cancer cells


New treatment for solid tumors announced

By Scott LaFee, UNION-TRIBUNE STAFF WRITER

Dr. Erkki Ruoslahti

Cancer scientists at the Sanford/Burnham Medical Research Institute in La Jolla said Thursday that they have developed a new way to attack solid tumors. The long-sought advancement delivers drugs deeper into the diseased growths, producing significantly more effective results while using smaller doses and producing fewer negative side effects.

In a paper published in the journal Science, Dr. Erkki Ruoslahti and his colleagues describe injecting lab mice with a variety of anti-cancer medications and a peptide — a chain of specific amino acids. These special immune-deficient mice carried human forms of breast, prostate and pancreatic cancers.

The peptide is key.

During the 1980s, Ruoslahti showed that a peptide called RGD possessed the ability to find and attach itself to receptors on solid tumor cancer cells. Last year, he published a paper reporting that a variant of RGD called iRGDnot only homed in on cancer cells, but activated their internal transport systems so that the peptide was essentially passed through cell after cell, moving ever-deeper into a tumor.

The new report, co-authored by others including Dr. Kazuki N. Sugahara and Tambet Teesalu at the University of California Santa Barbara, shows that anti-cancer drugs lingering near peptide molecules get pulled into and through tumor tissues as well. That enables them to attack cancer cells previously beyond their reach.

“This may be a very important innovation,” said David A. Cheresh, a professor of pathology at the Moores Cancer Center, part of the University of California San Diego. “We have plenty of drugs that work. The problem has always been getting the drugs to the right location.”

By their nature and architecture, solid tumors are well-equipped to fend off anti-cancer drugs. Tumors have poor vascular systems, which reduces exposure to blood-borne drugs. They are densely fibrous, which serves as a kind of physical armor. And they have high internal pressures, which means “anything trying to get in is basically swimming upsteam,” said Ruoslahti.

The iRGD peptide acts like a key, switching on the internal transport system of cancer cells so that they actively pull inside anything that’s knocking on certain surface receptors.

Based upon early findings, the approach promises to have wide application. Researchers say the iRGD peptide penetrates many tumor types and might be useful in treating most, if not all, solid tumor cancers. The peptide was also shown to enhance the therapeutic effects of multiple existing anti-cancer medicines, including a small molecule drug, a monoclonal antibody and two nanoparticle drugs.

In tests, some mouse tumors that showed resistance to one drug alone were effectively treated when the drug was co-administered with the peptide. Other tumors that only partly responded to a drug were eradicated by the combined approach.

Another encouraging aspect of the research, said Ruoslahti, is that the peptide and anti-cancer drugs are effective together without being chemically attached to each other. That may simplify the path to actual clinical use because no new drug or chemical entity is being created, which would require extensive, original testing to prove its efficacy and safety.

“This could cut years off the testing process,” said Ruoslahti.

Cheresh cautioned, however, that more research must still be done in animal models and in humans, including clinical trials to determine dosage safety and whether what works in mice works in people.

“It’s still early in the process,” he said. “But at the end of the day, I can see how this approach or something like it could lead to more efficient therapies. It could change the way we treat cancer patients.”

Solid tumor cancers are diseases in which abnormal masses of tissue form. They may be either benign or malignant. According to the latest United States Cancer Statistics (2006), published by the Centers for Disease Control and Prevention, the top 10 cancers (based on incidence rate) are all solid tumor types.

  1. Prostate 152.6 (per 100,000 people)
  2. Female breast 119.3
  3. Lung and bronchus 66.8
  4. Colon and rectum 46.8
  5. Corpus and uterus 23.7
  6. Urinary bladder 20.5
  7. Non-Hodgkin lymphoma 18.7
  8. Skin melanomas 18.2
  9. Kidney and renal pelvis 15.0
  10. Ovary 12.3

Israelis make breakthrough in stem cell research


Hadassah Hospital researchers develop new cell growth method which may help heal Parkinson’s disease, diabetes

Sarit Rosenblum

Fetal stem cells. Considerable scientific interest

A breakthrough made by Israeli researchers may pave the way for healing chronic illnesses: Researchers from Jerusalem’s Hadassah Hospital have developed a new method for producing large amounts of human fetal stem cells.

Fetal stem cells can transform into any type of cell in the human body. The cells attract considerable scientific interest due to the estimate that in the future they could be used as an endless source of cells, which will be transplanted and improve the performance of organs in a wide variety of degenerative diseases.

The medical world hopes to be able to use fetal stem cells to heal Parkinson’s disease, diabetes, reticular degeneration and other illnesses. In addition, the cells may be used in the future to grow human organs which would replace damaged organs like kidneys and liver.

Up to now, stem cells would be multiplied in colonies of one cell layer attached to a flat substrate. In their study, the Israeli researchers showed that human fetal stem cells can be produced and multiplied while floating in liquid substrate.

“The study’s findings are an important step ahead of an automatic and controlled creation of the large amounts of cells needed for transplant and other industrial and research purposes,” says Prof. Benjamin Rubinoff, director of the Hadassah Human Embryonic Stem Cell Research Center, who headed the team of researchers.

One step closer to the fountain of youth


It already has FDA approval for facial tightening and studies indicate that an Israeli company’s new cosmetic treatment device is safer, less painful, and more effective long-term.

Continue Reading

Pfizer R&D chief touts ‘golden age’ of drug discovery


By Simeon Bennett

Martin Mackay, Pfizer R&D Chief

Pfizer Inc., the maker of Viagra and the world’s biggest-selling drug Lipitor, said it expects to have more products with sales in excess of $1 billion as it develops treatments for Alzheimer’s disease, cancer and pain.

“We’re in the golden age of drug discovery,” Martin Mackay, president of pharmaceutical research at the New York- based company, said today in an interview with Bloomberg Television in Singapore. “We have a very replete pipeline in key areas such as cancer, Alzheimer’s disease, pain and inflammation” and infectious diseases.

Pfizer needs new products as it faces the November 2011 patent expiration of Lipitor, which accounted for $11.4 billion in sales last year, more than one-fifth of revenue. The company, the world’s biggest drugmaker, is also betting on treatments it got by buying rival Wyeth for $68 billion in October.

Nine of the company’s drugs sold at least $1 billion last year, according to data compiled by Bloomberg, qualifying them as “blockbusters.”

Mackay cited new products including tasocitinib for rheumatoid arthritis as among those that will replace lost revenue from cholesterol-controlling Lipitor. He also said the company will increase the variety of products it sells rather than try to replace one blockbuster with another.

‘Single-Digit Growth’

“The strategy at Pfizer is to be a very solid growing company, albeit with single-digit growth, and be a diversified company which not only has pharmaceuticals and new pharmaceuticals coming out of R&D, but nutritionals, consumer products, animal-health products, and the like,” Mackay said. “To contemplate double-digit growth is going to be difficult over the next period,” he said, referring to sales growth.

As of the end of last year, Pfizer had 26 drugs in phase- three trials, a final stage of testing required for U.S. approval, compared with eight at the end of 2007, Mackay said. That doesn’t include the treatments it got from Wyeth, he said at a briefing at the company’s research unit in Singapore.

Following the acquisition, Pfizer cut its research portfolio to 500 projects from 600, as it focuses on accelerating the development of drugs with a “big, early” effect in patient studies while weeding out the losers earlier in the process, Mackay said.

“Flatliners are flatliners, and they kill us unless you find them really early,” Mackay said. “In the next few years I think you’ll see less attrition, more survival of our compounds, and taking that attrition earlier.”

Clinical Trials

The company runs about 600 trials worldwide each year, including about 90 in phase one, the first stage of human testing, Mackay said. Of those, 23 were done last year in Singapore, a figure Pfizer wants to increase by about 10 percent this year as it tests more treatments for Asian populations.

Pfizer today said it will collaborate with closely held MicuRx Pharmaceuticals Inc., based in Union City, California, and China-based Cumencor Pharmaceuticals Inc. to develop antibiotics for drug-resistant tuberculosis in China. Pfizer will pay an undisclosed upfront fee, fund the discovery and development of the antibiotics and make payments linked to marketing the products, it said in a statement.

China has more than 25 percent of the world’s multi-drug resistant tuberculosis, Pfizer said, citing the World Health Organization.

Pharma M&A: 10 years, 1,345 deals, $694B


Global Business DealsDuring the 10-year period ended December 31, 2009 a total of 1,171 mergers and acquisitions of biotechnology companies were announced, with disclosed prices totaling more than $295 billion. Each of the 25 largest biotechnology mergers and acquisitions was valued at a price greater than $1.6 billion. Leading acquirers for the decade include Roche, AstraZeneca, GlaxoSmithKline, Amgen, Eli Lilly & Co. and Genzyme Corporation.

The largest deal by far among biotechnology mergers and acquisitions announced in the 10-year period ended December 31, 2009 was Roche Holding AG’s $46.8 billion acquisition in 2008 of the remaining interest in Genentech. Roche had already acquired a majority interest in Genentech in 1990 and in the 2008 acquisition secured the 44.1% it did not already own. The next-largest among biotechnology mergers and acquisitions announced in the past 10 years was AstraZeneca’s $15.2 billion acquisition of MedImmune, announced in 2007.

All of the top 25 biotechnology mergers and acquisitions announced in the ten years ending December 31, 2009 involved a publicly-traded entity as the seller and also as the buyer. In 76% of the 25 largest biotechnology mergers and acquisitions announced in the 10-year period ended December 31, 2009, the target is a revenue-producing biotechnology company. However, among all 1,171 biotechnology mergers and acquisitions announced from 2000 to 2009 only about 18% of the companies targeted were producing any disclosed revenue at the time of acquisition.

Among the top 25 largest biotechnology mergers and acquisitions announced from 2000 through 2009, four companies announced multiple acquisitions: GlaxoSmithKline (4), Amgen, Inc. (2), Eli Lilly & Co. (2) and Genzyme Corporation (2). GlaxoSmithKline announced its $3.28 billion acquisition of the license for almorexant, a sleeping pill, in 2008, and for $2.11 billion GlaxoSmithKline acquired the rights to HuMax-CD20, a leukemia drug, in 2006. GlaxoSmithKline also forged a $1.94 billion alliance in 2007 with Galapagos NV to develop anti-infective pharmaceuticals and GlaxoSmithKline announced its acquisition of ID Biomedical for $1.62 billion in 2005.

Amgen announced its $11.1 billion acquisition of Immunex in 2001 and Amgen announced its $2.65 billion acquisition of Abgenix in 2005. Eli Lilly and Co. announced its $6.5 billion acquisition of ImClone Systems in 2008 and Lilly announced its $2.3 billion acquisition of Icos Corporation in 2006. Genzyme Corporation announced its $2.8 billion acquisition of the Bayer hematologic oncology portfolio in 2009 and Genzyme announced its $1.9 billion acquisition of the worldwide license for mipomersen from Isis Pharmaceuticals in 2008.

Biotechnology Mergers and Acquisitions, 2000 to 2009
Year     Dollars Committed     Number Of Deals
2009     $47,523,349,040           193
2008     $93,879,257,347           148
2007     $42,105,127,700           145
2006     $36,407,170,500           115
2005     $23,196,902,050            113
2004     $6,764,873,000                96
2003     $16,681,231,200             128
2002     $3,274,727,708                96
2001     $20,150,840,000              85
2000     $5,076,797,094                52
Totals     $295,060,275,639     1,171

Only about 18% of the biotechnology companies that were targeted in mergers and acquisitions announced during the 10 years ended December 31, 2009 were producing disclosed revenues at the time of the announcements. Among the top 25 mergers and acquisitions for the same period, 76% of the biotechnology companies targeted were producing revenues at the time the deals were announced.

Most of the top 25 largest biotechnology mergers and acquisitions announced during the 10-year period ended December 31, 2009 targeted a United States-based concern, although seven of the top 25 mergers and acquisitions targeted entities based in Europe. Most of the acquirers in the top 25 biotechnology mergers and acquisitions announced from 2000 to 2009 were also U.S.-based, but also included acquisitions announced by eight companies based in Europe, one in Canada and one in Japan.

Geographically, for the 10-year period ended December 31, 2009, the states that were home to the acquirers in the greatest numbers of biotechnology mergers and acquisitions included California, New York, Massachusetts, New Jersey, Maryland, Pennsylvania, North Carolina, Washington and Texas. Outside the U.S., the countries that were home to the acquirers in the greatest numbers of biotechnology mergers and acquisitions included Switzerland, Germany, England, Netherlands, Japan, Canada, France, Australia and Denmark. On the sell-side, for the same 10-year period, the states that were home to the targets in the greatest numbers of biotechnology mergers and acquisitions included California, Massachusetts, Maryland, New York, New Jersey, Washington, Pennsylvania, North Carolina and Texas. Outside the U.S., the countries appearing most frequently as the home base of the target included Canada, England, Switzerland, Germany and France.

During the 10-year period ended December 31, 2009 a total of 1,171 mergers and acquisitions of biotechnology companies were announced, with disclosed prices totaling more than $295 billion. Each of the 25 largest biotechnology mergers and acquisitions was valued at a price greater than $1.6 billion.

Is the DNA patent dead?


Biotech companies argue that a judge’s ruling against DNA patents will slow their life-saving work. Instead they should move quickly to come up with a better, more collaborative way to protect and share findings. Time to get creative.

By David Ewing Duncan

Who owns our DNA — those long sequences of As, Gs, Ts, and Cs that make us who we are and contain hidden clues to diseases that might one day afflict us? Until yesterday, companies, universities, and individuals could make a claim, patenting DNA sequences isolated from the human body, though not the actual genes inside of you and me.

The whole framework around grabbing control revolved around creative lawyering, with companies over the last few years figuring out ways to adopt intellectual property laws better suited for, say, toasters — or man-made drugs — than to biological structures that seem to be more like leaves or sunshine.

Now it’s time for that innovative spirit to move away from the general counsel’s office and back to the lab.

The shift came yesterday in a case that has pitted the American Civil Liberties Union and several scientific and patient advocacy groups against Myriad Genetics (MYGN) — which owns patents on two genes that can contain mutations associated with breast cancer. Judge Robert Sweet, of the U.S. District Court of the Southern District of New York, invalidated these patents, saying they were “improperly granted” because they involve a “law of nature.”

“Many, however, including scientists in the fields of molecular biology and genomics, have considered this practice a ‘lawyer’s trick’ that circumvents the prohibitions on the direct patenting of the DNA in our bodies but which, in practice, reaches the same result,” Sweet wrote in a 152-page decision.

If this ruling survives appeals that could reach the U.S. Supreme Court, it could invalidate thousands of gene patents and cause problems for any company or lab that has invested in or will invest in developing predictive or diagnostic tests for hundreds of diseases. It also may impact the development of drugs based on owning the rights to certain genes, though this ruling is not likely to impact patents of genetic sequences that are part of a process used to create man-made drugs.

Myriad and other defendants in the case, including the U.S. Patent Office, have not yet commented on the ruling. In an interview two weeks ago, Myriad General Counsel Richard Marsh said that the company would likely go all the way to the Supreme Court if necessary. “The patent system works,” he said. “Without patents told who is going to do the work and spend the money to make this product accessible to people?”

Already, our DNA is being used to detect and predict risk factors for breast cancer and other common diseases, and for dozens of rare disease such as Tay Sachs and Huntington’s. Physicians also can use gene markers to screen people to see if specific drugs will work for them or not.

One innovative idea would be to explore other solutions to creating intellectual property around naturally occurring entities in order to attract investment to develop products based on this entity. I suggested looking into the system of assigning and licensing frequencies on the electromagnetic spectrum that provides us with radio stations, GPS signals beamed in from satellites, and, yes, cell phone wavelengths.

At the end of the 19th century, the invention of radio caused a previously unknown spectrum of radio frequencies to be discovered — a finding not unlike that of the human genome a century later — which led to a system of public ownership and government licenses issued to companies that now range from Verizon (VZ) and AT&T (T) to your local hip-hop station. Licensees are required to follow certain rules or risk fines or (rarely) the forfeiture of their license.

As the industry and tech transfer offices in universities decry this legal outcome and gear up to fight it on appeal, they might consider that patents are not the only way to create intellectual property.

The issue of patenting an “isolated” gene, which is a copy of a “real” gene, has always stretched credulity. For years it has angered researchers and patient groups who want a system that does not create gene monopolies that can hinder further research into the genetic roots of disease, can charge exorbitant prices for tests, and can block attempts by patients to get second opinions on diagnostic tests that remain in many cases experimental.

“Today’s ruling is a victory for the free flow of ideas in scientific research,” said Chris Hansen, a staff attorney with the ACLU in a press release. “The human genome, like the structure of blood, air or water, was discovered, not created. There is an endless amount of information on genes that begs for further discovery, and gene patents put up unacceptable barriers to the free exchange of ideas.”

Arguably, the endless controversies have actually slowed innovation: Investors hesitate to commit millions of dollars to developing new diagnostic tests and even drugs given the uncertainty over patents.

Judge Sweet’s decision will cause much more turmoil in the weeks and months to come as the appeal process plays out. Even if other courts side with Myriad, the rulings are likely to be very narrow, perhaps covering only very specific mutations within genes.

This is unlikely to settle the matter, however — which suggests that life science lawyers and executives (and lobbyists) might consider borrowing some of those creative juices flowing so freely in the labs that are creating the new science in first place.

After Patent on Genes Is Invalidated, Taking Stock


By ANDREW POLLACK
Robert W. Sweet , Judge of United States District Court for the Southern District of New York

Robert W. Sweet , Judge of United States District Court for the Southern District of New York

Many biotechnology stocks fell on Tuesday as investors struggled to understand the impact of a ruling that threw out parts of two gene patents and called into question thousands more.

Stock market losses were muted, with two major indexes that track the shares of the industry falling by less than 1 percent each. In part, that was because biotechnology executives hastened to reassure their investors that the ruling would not necessarily undermine their businesses, at least in the short run.

But the executives themselves were struggling on Tuesday to figure out what the long-term impact would be. Biotech companies spend billions every year trying to develop new tests and treatments based partly on genes they have isolated and patented.

In a far-reaching ruling, Judge Robert W. Sweet anticipated a negative reaction from the industry. In a footnote of his 152-page ruling, he discounted fears that invalidating such patents would decimate the industry.

Some executives and lawyers who were interviewed on Tuesday disagreed with the judge’s legal reasoning. They also said that the ruling, even in the worst case for them, would take years to have a significant effect.

Eventually, if the judge’s reasoning is upheld on appeal, the invalidation of genetic patents could hit diagnostics companies, agricultural biotechnology companies and perhaps even traditional drug makers, though drugs are often protected by patents on their own chemical composition.

But the industry is already moving to a period of somewhat less dependence on DNA patents for its sustenance. Diagnostic laboratories, for instance, are shifting from testing individual genes to testing multiple genes or even a person’s entire genome. When hundreds or thousands of genes are being tested at once, patents on each individual gene can become a hindrance to innovation rather than a spur.

On Monday, Mr. Sweet, a United States district judge in Manhattan, ruled that parts of patents held by Myriad Genetics covering two breast cancer genes, known as BRCA1 and BRCA2, were invalid.

Myriad analyzes those genes in an expensive test that predicts whether a woman is at a high risk of getting breast or ovarian cancer. The plaintiffs in the case, which included various medical groups and the American Civil Liberties Union, said the patents on DNA were illegal and impeded access to the testing.

The decision invalidating the gene patents stunned many lawyers who follow such issues.

“It’s really quite a dramatic holding that would have the effect of invalidating many, many patents on which the biotechnology industry has invested considerable money,” said Rebecca S. Eisenberg, a law professor at the University of Michigan who has written widely on gene patents.

The Genomics Law Report, an Internet journal, called the decision “radical and astonishing in its sweep.” It headlined its article, “Pigs Fly.”

Although patents are not granted on things found in nature, the DNA being patented had long been considered a chemical that was isolated from, and different from, what was found in nature. But Judge Sweet ruled that the distinguishing feature of DNA is its information content, its conveyance of the genetic code. And in that regard, he wrote, the isolated DNA “is not markedly different from native DNA as it exists in nature.”

The immediate impact will be limited in part because the decision, made in a district court, does not apply to gene patents other than the ones it considered, and its value as precedent for other courts is limited.

Moreover, Myriad said Tuesday that it would appeal, and several lawyers said they expected the ruling to be overturned. Professor Eisenberg said “there isn’t a whole lot of doctrinal support” for considering DNA as information rather than as a chemical.

Even before an appeal is decided, the landscape could change in a way that would render the Myriad case moot. A ruling is expected soon from the Supreme Court in the so-called Bilski case. That case does not directly concern gene patents — it is about a fight over a method of hedging risk in commodities trading — but it gives the Supreme Court a chance to set new standards on what is patentable.

“We are still waiting, holding our breath for the Bilski case,” said Kari Stefansson, head of research at DeCode Genetics, which sells disease risk tests similar to those sold by Myriad.

If Judge Sweet’s decision were upheld on appeal, the impact could be more far-reaching. The biggest impact would be on companies like Myriad and Athena Diagnostics that offer diagnostic tests based on genes.

Some biotechnology investors and executives say that lack of patent protection for DNA could diminish investment and remove incentives to develop tests. That could slow the move toward so-called personalized medicine, in which genetic tests are used to determine which drugs are best for which patients.

James P. Evans, a professor of genetics at the University of North Carolina, said that would not necessarily be the case. There is thriving competition in areas like testing for mutations that cause cystic fibrosis or Huntington’s disease, even though no company has exclusivity.

“It’s quite demonstrable that in the diagnostic area, one does not need gene patents in order to see robust development of these tests,” he said.

GSK and Isis Pharmaceuticals Collaborate on RNA Therapeutics for Rare and Infectious Diseases. Isis will receive $ 1.53 B


– GSK has right to license and commercialize compounds at clinical proof-of-concept

– Isis gives GSK access to expertise in discovery and development of anti-RNA therapeutics

GlaxoSmithKline (NYSE: GSK) and Isis Pharmaceuticals, Inc. (Nasdaq: ISIS) announced today a new strategic alliance that will apply the Isis antisense drug discovery platform to seek out and develop new therapeutics against targets for rare and serious disease, including infectious diseases and some conditions causing blindness.

Under the terms of the agreement, which covers up to six programs, Isis will receive an upfront $35 million payment from GSK and is eligible to receive on average up to $20 million in milestones per program up to Phase 2 proof-of-concept (PoC). GSK will have the option to license compounds at PoC, and will be responsible for all further development and commercialization.  Isis will be eligible to receive license fees and milestone payments, totaling nearly $1.5 billion,

GSK

in the event all six programs are successfu
“As a platform, the Isis antisense approach offers us an exciting opportunity to target certain severe diseases in a way that has not previously been possible,” said Dr. Patrick Vallance, Senior Vice-President and Head of Drug Discovery at GSK.  “Isis Pharmaceuticals is a leader in antisense technology, and this new alliance will enhance our discovery platform in this promising research area.”lly developed for one or more indications and commercialized through to pre-agreed sales targets. In addition, Isis will receive up to double-digit royalties on sales from any product that is successfully commercialized.

Antisense therapies target the proteins involved in disease processes through the RNA that is involved in building these proteins. The Isis discovery platform develops specific therapies that bind to messenger RNA (mRNA) and inhibit the production of disease-causing proteins. Isis recently announced data from a Phase 3 trial in heterozygous familial hypercholesterolemia patients that demonstrated the therapeutic effect of this approach.

This alliance provides GSK with access to Isis’ expertise in drug discovery and development of RNA-targeted therapeutics, with Isis retaining responsibility for the discovery and development of compounds to the alliance targets from inception to PoC.

“We are excited to be working with GSK to apply antisense technology to these new therapeutic areas.  We are particularly excited to work on the novel targets GSK brought to the alliance,” said Dr. Stanley T. Crooke, Chairman and Chief Executive Officer of Isis Pharmaceuticals.  “This alliance is exactly the type of deal we want to do.  We retain control of the discovery and early development of our drugs while working together with a very high-quality partner to maximize the value of the drugs in late-stage development and commercialization.”

About RNA-targeted therapeutics

RNA-targeted therapeutics, or antisense therapies such as oligonucleotides, represent an opportunity for a new drug class.  Where most other medicines are small molecules or biologics that target a specific protein in a disease process, antisense therapies prevent protein synthesis by eliminating the mRNA – the template or pattern that guides the production of the protein.

Israeli Government expands biotech funds


blue dnaFour  biotech funds have met the threshold conditions of the government biotechnology fund tender.

The government originally planned to support three biotechnology funds from among the funds that met the threshold conditions, but has now decided to allow all four of the funds to receive the $24 million support, provided that each fund raises the $76 million supplementary financing. The decision will increase the government’s commitment to about $100 million from the originally planned $80 million, and will boost the program’s total funding to $400 million.

The government added that the fund that brings the largest amount of funding will win an additional special $8 million incentive funding.

The decision to allow each of the four funds that meets the tender’s terms to set up a biotech fund, provided that it raises the supplementary funding, prevents the problematic outcome of companies seeking to raise capital from their investors without knowing whether they will obtain government funding. The decision also indicates that the Ministry of Finance and the Ministry of Industry, Trade and Labor believe that all the funds that meet the threshold conditions are successful and worthy funds for establishing a biotechnology fund.

Adaptive TCR, a Fred Hutch Spinoff, Nabs $4.5M to Uncover Immune System Secrets


Luke Timmerman

Seattle experts in computer science and immunology are rallying around a new spinoff company from the Fred Hutchinson Cancer Research Center.

Seattle-based Adaptive TCR has nailed down a $4.5 million round of angel investment to get up and running, Xconomy has learned. The basic concept is to provide scientists with a high-speed, high-resolution look into the vast diversity of T-cells of the adaptive immune system that we all produce to ward off infections, and which sometimes go awry and cause disease.

This company wasn’t backed by the usual venture capital suspects in Seattle biotech, and it has an unusual backstory. Adaptive’s scientific co-founders are a pair of Hutch researchers who are first-time entrepreneurs in their 30s: Harlan Robins, a particle physicist who turned to genomics a decade ago to tackle its daunting math, and Chris Carlson, a geneticist and molecular biologist. Chad Robins, Harlan’s brother, has signed on as the founding president and CEO. Chad, who has a Wharton School business degree and experience with investment banking and hedge funds, wrote the original business plan and tapped his Rolodex to raise the company’s seed capital.

The founding scientific advisory board includes some big names. They include Arnold Levine of the Institute for Advanced Study in Princeton, NJ; Gerald Nepom, the director of the Benaroya Research Institute in Seattle; Edus Houston Warren of the University of Washington and Fred Hutch, as well as two other prominent genetic researchers from the UW who aren’t being named yet.

“I’ve been talking to my brother for 20 years, and saying ‘You’re a smart guy, when are we going to do a business together?’” Chad Robins says. “He’s never been interested before. Then he called me last February.”

That was a little over a year ago. Now the business is taking shape with a founding team of four employees who have subleased some office space in South Lake Union from VLST.

Adaptive TCR is built on using high-speed gene sequencing instruments that capture data from biological samples, and combining it with some pretty heavy duty math that’s executed by proprietary software.

The problem is certainly complicated enough to excite a string theorist like Harlan Robins. While scientists know that the 3 billion letters of DNA that make up a genome are consistent in every human cell, that’s not a fixed number that applies to immune system T-cells. The DNA in T-cells gets shuffled as they mature, allowing the cells to recognize a foreign invader like a virus. Humans have evolved an ability to adapt to these invaders, by building up a vast repertoire of T-cells with memory for a certain pathogen. This vast array of T-cell variation is something that scientists haven’t been able to look at in a high-volume, systematic way ever before. It creates a staggering diversity of possible ways humans respond to infection. For scientists trying to pinpoint the cause of, say, autoimmune disease, this also creates a classic needle-in-a-haystack problem.

Adaptive TCR hopes that by sequencing lots of blood samples from different individuals, and using its proprietary software, they can find some commonalities in the kinds of T-cell receptors that people form in certain situations, whether it is responding to a foreign pathogen like flu, or turning the immune system’s natural firepower on healthy tissue, like it does with rheumatoid arthritis. If scientists could find signature proteins on T-cells at the root of these immune system irregularities, then they could incorporate that knowledge into diagnostic products or use it to identify drug targets, Adaptive TCR says.

Few scientists have tried to look at these T-cell receptors in a high-output fashion before. Fewer than 30,000 T-cell receptors had been sequenced with conventional methods before the Adaptive TCR technique came along, Chad Robins says. The Adaptive TCR method claims to be able to identify 100 million T-cell receptor sequences over a four-day period.

The high-volume screening technology from Adaptive TCR “provides a sensitive and specific tool” for measuring patterns of T-cell variation, with “more resolution compared to techniques that we’ve used in the past,” says Nepom, the director of the Benaroya Research Institute. Chad Robins described it with an analogy: “These guys have invented the Hubble telescope compared to what we used to have, a pair of binoculars.”

So how is this supposed to become a business? It is starting out as a fee-for-service provider to academic and industrial customers who want to look at the diversity of T-cells. People ship their samples to Adaptive TCR’s offices, and get back a result on the T-cell diversity and repertoire from the sample. Adaptive isn’t spending big money on its own servers to host this data—those gigabytes are being stored on secure remote servers operated by Amazon Web Services.

The fee-for-service model can certainly generate revenue early on to sustain the company, but that’s not the end of the story.

Adaptive TCR has some other ideas on how to capture more of the future value that this data on T-cells might create for diagnostics and drug discovery. Autoimmune diseases—in which the immune system goes haywire and starts attacking healthy tissues like a virus—affect an estimated one out of every 12 people in the U.S. with more than 80 different conditions, according to the National Institutes of Health. They are notoriously hard to diagnose, because there’s not a good molecular tool for that, Robins says. By getting high-resolution looks at T-cell receptors, Adaptive TCR hopes to find some of the basic immune system malfunctioning at a molecular level that hasn’t been seen before, which could provide for much earlier diagnosis.

While there is a huge amount of variation in the genetics of T-cell receptors in one individual, Adaptive TCR also thinks it’s possible that there are overlapping stretches of DNA in these T-cell receptors shared between patients with an autoimmune disease like Type 1 diabetes or multiple sclerosis, Robins says. The company has a collaboration with Nepom’s team at the Benaroya Research Institute to look for those overlapping stretches, which could become valuable new drug targets.

Of course, these are still early days at the company. Harlan Robins and Chris Carlson are keeping their faculty positions at the Hutch. Much will depend on whether the early customers think they are getting their money’s worth by getting all this data on T-cell diversity over the coming year. Proof to show the value of the method will take time to emerge in peer-reviewed literature. The founders, whom I met a few weeks ago during a visit to the Hutch, didn’t sound like they are getting too carried away with themselves yet.

“These guys came up with this, and it’s my job not to screw it up,” Chad Robins says. “They’ve invented something extraordinary, but the invention still needs to be brought to the market.”

Tumors Use a Protein to Hide From Immune System


New research from Switzerland provides insight into how tumors remain undetected by the body’s immune system by mimicking lymph nodes.

Prof. Melody Swartz

“The tumor tricks the body into thinking it is healthy tissue,” lead author Melody Swartz, head of the Laboratory of Lymphatic and Cancer Bioengineering, said in a news release about the study, published online March 25 in Science.

According to Swartz and her colleagues at the Ecole Polytechnique Federale de Lausanne, the findings could lead to better treatments for cancer.

In the study, the researchers focused on a protein that is typically found in lymph nodes and discovered that certain tumors can secrete the protein, making them appear to be lymph nodes. This disguise allows the tumors to manipulate immune cells known as T-cells, just like lymph nodes do, the study authors explained.

The findings have “important implications for tumor immunotherapy,” Jacqui Shields, another researcher, explained in the news release

In pursuit of CNS pipeline, Biovail buys compounds from Cortex


Cortex PharmaceuticalsLast year, Canada’s Biovail announced it was refocusing its business and gearing up to spend $600 million on new CNS therapies through 2012. Biovail subsidiary Biovail Labs today announced that it’s purchased Cortex Pharmaceuticals’ Ampakine compounds for respiratory depression, a brain-mediated breathing disorder.

Biovail’s haul includes Phase II compound CX717, the preclinical compounds CX1763 and CX1942, and the injectable dosage form of CX1739. The company paid Cortex an upfront fee of $9 million and expects to pay an additional $1 million upon the completion of a transition period. Biovail could also fork out up to $15 million in potential milestones.

“This acquisition, our eighth transaction since we launched our specialty CNS strategy, adds another promising compound to our emerging development pipeline,” says Biovail CEO Bill Wells. “CX717 has the potential to address a significant unmet medical need, and would fit nicely with the Hospital sales force we intend to deploy for Staccato loxapine.”

The Canadian developer has been snapping up CNS products left and right since unveiling its new strategy. Santhera Pharmaceuticals signed a $192 million licensing pact with Biovail for its experimental drug for dyskinesia in Parkinson’s disease. Alexza Pharmaceuticals got $40 million upfront and could earn $90 million in milestones for its inhaled agitation therapy. And Acadia Pharmaceuticals landed $30 million upfront and stands to earn up to $365 million in milestones for its Parkinson’s disease psychosis treatment.

Rise in obesity makes VCs hungry for startups


Joanna Glasner

SAN FRANCISCO (Private Equity Week) – Startups focused on treatments for metabolic disorders – one of the key contributing factors in obesity – have raised significant sums of venture capital in recent months.

A competitor stands before judges at a casting call for the second season of the reality television programme ”Dance Your Ass Off”, during which overweight or obese contestants hope to lose weight by dancing, in New York, December 18, 2009.

For these startups, developing treatments for weight disorders is less about controlling the calories consumed and more about focusing on the metabolic systems that regulate how the body uses food.

Last week, Boston-based Rhythm Pharmaceuticals, another new entrant to the obesity field, announced that it has raised $21 million in a Series A funding round from MPM Capital and New Enterprise Associates.

Rhythm is developing treatments for metabolic diseases based on peptide hormones, protein compounds instrumental in introducing changes to a cell’s metabolism. President Bart Henderson said that the company plans to begin clinical trials of two peptide-based treatments in the next two years.

“The obesity pipeline has been relatively thin,” said Henderson, who incubated the company while he was an entrepreneur-in-residence at MPM. “Since obesity and diabetes together are such important health priorities, the clinical development pipeline is in dire need of new approaches.”

Rhythm also announced last week that it licensed compounds and intellectual property related to two peptide hormones from Paris-based biotech company Ipsen. The compounds, ghrelin and melanocyte-stimulating hormone (MSH), are involved in regulating food intake, energy levels, and gastrointestinal function. Henderson said MSH-related therapeutics, linked to signaling systems in the body that regulate appetite and energy, will be targeted to patients suffering from both obesity and diabetes.

Pharmaceuticals tied to ghrelin, which is involved in regulating nutrient uptake and gastrointestinal activity, will focus on potential treatments for gastrointestinal disorders, including diabetic gastroparesis, a condition in which food remains in the stomach for longer than normal, according to Henderson.

Under the terms of the license agreement, Ipsen will receive up to $80 million in payments upon achievement of certain clinical milestones and in royalties on future products. Ipsen will also acquire 17 percent of equity in Rhythm and have a seat on its board of directors.

Given the high and growing global incidence of obesity, it’s no surprise that startups developing new treatments are seeing interest growing from investors.

GROSS STATISTICS

The World Health Organization projects that by 2015, about 2.3 billion adults will be overweight and more than 700 million will be obese. As of 2005, the WHO estimated that at least 400 million adults worldwide were obese, defined as having a body mass index (BMI) of more than 30. (BMI equals weight in kilograms divided by the square of height in meters.)

In addition to Rhythm, other companies that have raised sizeable venture rounds in the past several months for obesity treatments include:

* GI Dynamics, based in Lexington, Massachusetts, raised $15 million in late stage funding in January, according to a securities filing. The company, which develops devices for treatment of obesity and diabetes that can be delivered into the gastrointestinal tract using minimally invasive techniques, has raised $76 million since 2003. Backers include Advanced Technology Ventures, Johnson & Johnson Development Corp., Domain Associates, Medtronic Inc., Polaris Venture Partners, Catalyst Health and Technology Partners and Technology Partners and Cutlass Capital.

* Satiety, based in Palo Alto, California, raised $25 million in late stage funding in September, according to a regulatory filing. The company, which develops minimally invasive treatments for obesity and tools used in weight loss surgery, has raised $86 million since 2001 from Morgenthaler Ventures, Venrock Associates, HLM Venture Partners, Three Arch Partners, Skyline Ventures and Pinnacle Ventures.

* Elixir Pharmaceuticals, based in Cambridge, Massachusetts, raised $12 million in late stage funding in May to develop pharmaceuticals for the treatment of metabolic diseases based on compounds that stimulate interactions between genes and enzymes. Backers in the last round include MPM, ARCH Venture Partners, Oxford Bioscience Partners, the Omega Fund and Physic Ventures. The company has raised $115 million since 2000.

* ValenTX, based in Carpinteria, California, raised $22 million in September to develop an implantable medical device to treat morbid obesity. The company has raised $28 million since 2002 from SV Life Sciences Advisors, EDF Ventures, Affinity Capital Management, Kaiser Permanente Ventures, Sapient Capital Management, TGap Ventures and Covidien Ventures.

Pill could end the misery of period pains


A pill that could cure the cause and not just the symptoms of period pains is being developed by British scientists.

By Richard Alleyne, Science Correspondent

Up to 90 per cent of women of childbearing age suffer from cramps caused by period pains and take painkillers to relieve the symptoms.

But now they might no longer have to soldier on stoically after researchers have developed a pill which could put an end to the root cause of their discomfort.

The condition, called dysmenorrhoea, is the leading cause of absenteeism from school and work among women in their teens and 20s.

“We hope that the drug will provide a more effective treatment option for millions of women worldwide with this painful condition,” said Andrzej Batt who leads the development team at Vantia Ltd in Southampton.

“Dysmenorrhoea not only diminishes the quality of life for millions of women, but also has a hidden, society-wide economic cost that involves an enormous number of days lost from work and school.”

Mr Batt pointed out that dysmenorrhoea affects between 45 and 90 per cent of women of child-bearing age,

In addition to pain in the abdomen and back, symptoms may include nausea, vomiting, sweating, and dizziness.

Existing treatments for the condition include pain-relievers, anti-inflammatory drugs, and oral contraceptives that stop menstruation.

However, these treatments are ineffective in almost one-third of women with moderate to severe cases.

Some of them relieve only the symptoms, rather than targeting the underlying cause of dysmenorrhoea, and may have unwanted side effects such as mood alteration and stomach upsets.

Menstrual cramps are caused by contractions of the uterus during menstruation. In dysmenorrhoea, the uterus contracts with increased frequency, causing unusually severe, cramping pain.

The cause, scientists believe, is increased blood levels of the hormone vasopressin, which plays a role in regulating contraction of the uterus. The Vantia scientists reasoned that blocking this hormone might relieve dysmenorrhoea.

Their search for such a potential drug involved shifting through hundreds of chemical compounds and led to one with the desired effects.

Scientists then re-engineered the compound, known by the code word, VA111913, to fine-tune its effects.

One modification allowed the drug to be administered orally, as a pill, rather than in an injection. If studies continue to show promise, the drug could be available to patients in four years, the scientists say.

The scientists described the study at the American Chemical Society annual meeting in San Francisco.

http://www.telegraph.co.uk/health/healthnews/7506915/Pill-could-end-the-misery-of-period-pains.html

Lilly's CEO Eyes German Market


By ALLISON CONNOLLY

FRANKFURT—After weighing in on health-care reform debate in the U.S., Eli Lilly & Co. Chief Executive John Lechleiter is turning to Europe, where he is not only eyeing local reform efforts but also potential acquisitions to expand the company’s presence here.

John C. Lechleiter, chief executive of Eli Lilly, discusses health-care reform efforts in the U.S. and Germany. He also talks about the challenges facing his firm, including the expiration of several key patents by 20Lechleiter is turning to Europe, where he is not only eyeing local reform efforts but also potential acquisitions to expand the company's presence herMr. Lechleiter plans to travel to the Germany capital of Berlin Thursday to speak to with government officials who are considering changing the way drugs are paid for in Germany and curbing the price for some.

John C. Lechleiter, chief executive of Eli Lilly, discusses health-care reform efforts in the U.S. and Germany. He also talks about the challenges facing his firm, including the expiration of several key patents by 2013.”We want to make sure that’s a discussion about value and not just about cost,” he said in an interview here on the sidelines of a U.S. Chamber of Commerce event. “If it’s just about cost, then it comes down to levying what amounts to a tax.”

While drug companies have better access to the German market than those in other countries because reimbursement is granted immediately after products receive market approval, Mr. Lechleiter said market penetration of new products here five years after approval is among the lowest in Europe. He noted that seven out of every 10 drugs prescribed in Germany are generic.

“No one at Lilly has ever referred to Germany as a cash cow for our business,” he told the Chamber of Commerce event, when asked why residents pay more for drugs overall here than in neighboring countries.

Specifically, he’s taking aim at a measure officials here are considering that would determine drug reimbursement based on how much more beneficial a new drug is over existing therapies. He believe this approach is unfair because some patients respond better to certain drugs than others, based on their genes.

Mr. Lechleiter said he would like to expand his company’s presence in Europe beyond Germany through acquisitions or licensing deals. He’s particularly interested in assets operating in the areas of diagnostics, diabetes care and drug delivery technologies.

Earlier this year Eli Lilly purchased the rights to Pfizer Inc.’s animal health assets in Europe.

Mr. Lechleiter said he’s still confident in Eli Lilly’s anti-clotting drug Effient, which he hopes will garner market share from Sanofi-Aventis’s and Bristol-Myers Squibb Co.’s top seller Plavix, whose patent expires in 2012.

But while proven more effective at preventing clots than Plavix in a major study, Effient also showed increased risk for bleeding.

Mr. Lechleiter signaled that the company may try a new approach with the drug, tailoring marketing to groups of patients that respond better to Effient based on their genetic makeup.

Eli Lilly faces its own patent challenge in the next few years as those on four out of its five biggest sellers are set to expire by 2013. Mr. Lechleiter said there may be declines in a given year when the company loses a big patent—but the company plans to spend more on research and development this year than last year in order to push four drugs through Phase III trials to market.

“Our stock price hasn’t moved much but that’s because our investors really want to see progress in that pipeline,” he said. “As we generate more and more data, investors will be less skeptical of our ability to overcome these patent challenges.”

Write to Allison Connolly at allison.connolly@dowjones.com

Gene test helps select breast cancer chemotherapy


Kate Kelland::LONDON

Scientists have found a new and simple way to identify breast cancer patients who are likely to respond well to treatment with a common class of chemotherapy drugs, and predict who is unlikely to see any benefit.

The findings presented by researchers at the European Breast Cancer Conference in Spain on Thursday, mean doctors should be able to test patients, tailor treatment to them and avoid giving them toxic drugs that will not help.

By conducting a study called a meta-analysis of four large breast cancer trials including nearly 3,000 patients, the researchers found that an abnormality on chromosome 17, called CEP17, is a “highly significant indicator” that the tumor will respond to chemotherapy drugs called anthracyclines.

Anthracyclines are anti-tumor antibiotics that interfere with enzymes involved in DNA replication. They are widely used against a variety of cancers.

“Our aim was to identify patients for whom anthracyclines provided benefit … and to seek to ensure that future treatment was targeted to this group,” John Bartlett of Britain’s Edinburgh University, who led the study, said in a statement.

After adjusting for factors relating to the tumor and its treatment, the researchers found that if patients with CEP17 were treated with anthracyclines, they were around two-thirds more likely to survive, and to survive without a recurrence of cancer, than those not treated with anthracyclines.

“This suggests that only those patients with CEP17 tumors should receive anthracyclines,” Bartlett said.

The results provide more tools for doctors to make personalized, or tailored, medicine a reality in cancer care.

CEP17 is on the same chromosome as other genes known to be involved in breast cancer, such as HER-2, and can be detected with a simple test called fluorescent in situ hybridization, or FISH, which is carried out routinely in breast cancer patients.

Doctors can already also test for certain genes to tell whether a woman’s breast cancer is sensitive to estrogen and likely to benefit from hormone-blocking drugs like tamoxifen.

And patients whose breast tumors are HER-2 positive are often given the drug Herceptin, made by Roche Holding AG, which only works against these kinds of tumors.

Bartlett said the existence of a readily available test for CEP17 meant doctors could immediately start to better tailor chemotherapy to patient needs. He said extra work on CEP17 was needed to see if it could reveal more about breast cancers.

“It (CEP17) works as a biomarker for predicting response to anthracyclines, but we don’t know why it works. So our next step is to discover this and to try to make the cancers that don’t have the marker behave like the ones that do,” he said.

U.S. researchers published a study in January that found that changes in two genes on a small region of chromosome 8q made tumors resistant anthracyclines, but not other types of chemotherapy drug.

(Editing by Sharon Lindores)

Israel: Aiming to beat diabetes


Diabetes is now reaching epidemic proportions. The chronic disease occurs when the pancreas does not produce enough insulin, or the body cannot effectively use the insulin it does produce. Over time this leads to serious damage to the body – particularly the nerves and blood vessels – causing blindness, loss of limbs, and eventually death.

In the US alone 23.6 million people (7.8 percent of the population) have diabetes, while worldwide the World Health Organization claims that some 180 million people suffer from the disease. In some communities around the world – like Oklahoma – a staggering 39 percent of the population has pre-diabetes or diabetes.

The figure is rising dramatically. WHO predicts that this figure will double by more than 50 percent in the next 10 years worldwide, and 80 percent in upper-middle income countries, if something isn’t done urgently to combat the disease.

The primary causes of Type 2 diabetes – the most common form of the illness – are obesity, lack of exercise. In the past most people tended to develop this in the middle years, today the age is creeping lower and lower.

Israeli scientists are at the forefront of research into diabetes, searching for ways to diagnose the illness at an earlier stage, create more effective and pain-free treatments, help treat the side effects of the disease, and understand how this disease develops in an effort to find a cure.

Breakthrough diabetes research may be closest thing to a cure [VIDEO]

The World Health Organization estimates that over 180 million people worldwide have diabetes and predicts that will more than double by 2030.

Israeli proposes to shrink Samoan waistlines

An Israeli diplomat in Samoa is bringing Israeli experts to curb increasing obesity and diabetes in the South Pacific islands.

New oral insulin capsule passes Phase 2 clinical trials

Israel drug delivery systems developer Oramed Pharmaceuticals, has reported positive results from a Phase 2A study of its oral insulin capsule, ORMD-0801, on type 1 diabetic patients.

Haifa scientists close in on new diabetes treatment

Thanks to ongoing research at the University of Haifa, it may soon be possible to treat diabetes by popping a pill instead of an injection.

Israeli patent moves closer to achieving oral insulin treatment

When Dr. Miriam Kidron, a scientist from Hadassah University Hospital in Jerusalem, first announced that she and a group of fellow researchers planned to bring an oral insulin for diabetics to market, most people thought the idea was ridiculous.

Israeli startup turns mother’s herbal remedy into a diabetes treatment

For Israeli Bedouin Dr. Sobhi Sauob, it was only natural to turn to his mother when he decided to start developing a new herbal remedy to help diabetics.

Scientists develop protein to regrow blood vessels

A new protein injection developed by Israeli researchers can trigger the regrowth of blood vessels around the heart, offering a potential alternative to risky bypass surgery.

Landmark Israeli-led study to improve diagnosis of diabetes

The World Health Organization, the US National Institute of Health and others are expected to change their definition of gestational diabetes, based on an international study led by an Israeli medical team.

Natural Israeli remedy holds out hope for diabetes sufferers

There’s nothing like a hot cup of tea on a cold day. Now an Israeli company plans to introduce a herbal tea to the US that isn’t just an enjoyable break, but which it claims can substantially reduce the blood sugar levels of diabetics.

Technion researchers find that vitamin E can help diabetics avoid heart attacks

Researchers at the Technion-Israel Institute of Technology and Clalit Heath Services have discovered that taking vitamin E supplements could reduce the risk of heart attacks and stroke in type II diabetics who carry a specific version of a gene.

Pfizer puts funds behind team of Israeli all-star scientists to change traditional diabetes research

It’s become a given that Israel is a world leader in high tech and biotechnology – areas driven by doctors and scientists often with spirited visions of making the world a better place. So wouldn’t it make sense to bring together some of the top Israeli minds in a given field to form a dream-team of physicians and scientists?

Israel set to become world center for diabetes research

Israel’s contribution to the worldwide effort to find a cure for diabetes received a big boost last week when a five-year, $30 million program was launched in Jerusalem.

Israeli-Swedish team uncovers key to onset of Type 2 diabetes

Scientists at the Weizmann Institute of Science in Rehovot and the University of Umea in Sweden have unraveled a mechanism by which fat contributes to the onset of the Type 2 diabetes, which affects one out of 12 adults in the Western world and threatens to double in the next two decades, The Jerusalem Post reported.

Israeli couple finds sleep apnea may extend life


Periodic breathing cessation during slumber can lengthen seniors’ lives.

Sleep apnea syndrome – in which sufferers stop breathing momentarily many times during the night – has for many years been regarded as a major risk factor for clogging of the coronary arteries and other heart diseases. But now, Technion-Israel Institute of Technology President Prof. Peretz Lavie – a psychologist and one of the country’s leading sleep medicine experts – and his wife and fellow researcher cell biologist, Dr. Lena Lavie, have found that in elderly people, moderate apnea may in fact extend their lives rather than shorten it.

The Lavies’ research, based on the study of 611 individuals with a mean age of 70 and a follow-up period of about five years, has just been published in the Journal of Sleep Research of the European Sleep Research Society. The reasoning has been confirmed separately by German researchers at Heinrich Heine University in Dusseldorf, who published their findings in the journal Chest of the American College of Chest Physicians.

Prof. Lavie has published more than 340 scientific articles and eight books in the field of sleep research, including The Enchanted World of Sleep, which is suited for the layman and translated to 15 languages. Lena, a senior researcher in the Technion, has collaborated with him on sleep research focusing on understanding the cellular and biochemical impacts of the breathing cessations.

Many sleep apnea patients go to bed at night connected to a continuous positive airway pressure (CPAP) device, which is not very comfortable but pushes through a mask pressurized air – insufficient during breathing cessation – under pressure into their lungs. This does not cure sleep apnea but can reduce the complications.

Intermittent hypoxia – the lack of adequate oxygen – initiates a cascade of events involving oxidative stress and inflammatory processes leading to atherosclerosis. But surprisingly, the new research found that in contrast to young and middle-age patients, who showed significantly higher mortality than their counterparts in the general population, elderly patients with mild or moderate apnea showed significantly lower mortality than in the general population.

The researchers suggest that the hearts of elderly sleep apnea patients get blood from a larger number of arteries – called collaterals – that develop by angiogenesis due to the lack of oxygen supply, than the hearts of patients without sleep apnea. This additional blood supply protects them if they suffer a heart attack, the Lavies write.

The Haifa researchers based their hypothesis on previous results from the Haifa group demonstrating that sleep apnea patients have in their blood high levels of a protein called vascular endothelial growth factor (VEGF). This protein is responsible for the growth of new blood vessels, and its production is triggered by a drop in blood oxygen levels.

The Technion team also showed that there are very large individual differences in the effect of hypoxia on the production of this protein. The research group found that individuals who could produce a large amount of protein when exposed to hypoxia had more blood vessels around their hearts in comparison with individuals who could not produce the protein.

Dr. Stephan Steiner and his colleagues from the cardiology department in Heinrich Heine University reported data that provided strong support to the Lavies’ hypothesis. Steiner and his colleagues compared the number and size of the heart collaterals measured by catheterization in patients with and without sleep apnea and reported that patients with sleep apnea had significantly more collaterals than patients without sleep apnea, even though there were no differences between the groups in age, weight, heart condition or use of medication.

The German research in Chest was accompanied in the same issue by an editorial that was written by the Lavies. “If confirmed, these findings may have important clinical implications regarding treatment of the syndrome. Moreover,” they continued, “such findings – if combined with individual gene analysis – may provide new treatment strategies for cardiovascular protection.”

OriGene’s TrueMAB monoclonal antibody collection gets $16 M investment


ROCKVILLE, Md., —  OriGene Technologies, Inc., a leading gene-centric life sciences company, announced the completion of a $16 million Series B financing. OriGene’s previous investors also participated in this round.  The proceeds from the funding will be used to continue to build OriGene’s TrueMABTM monoclonal antibody collection.

“We are delighted by this vote of confidence from our existing and new investors and share their enthusiasm for our growth strategy and execution.  The funding will propel us closer to meeting our goal of building the largest monoclonal antibody collection in the world covering the entire human genome of approximately 20,000 genes,” said Wei-Wu He, OriGene’s Chairman and Chief Executive Officer.

The TrueMABTM Collection of monoclonal antibodies will be developed with the most up-to-date antibody technologies and will be significantly different from many antibodies on the market, as OriGene will be using authentic human full-length proteins as immunogens during the manufacturing process. OriGene has dedicated the last decade to build the largest collection of human full-length cDNA clones in the world. The collection has enabled OriGene to manufacture human full-length proteins directly from human cells for producing monoclonal antibodies. TrueMABTM monoclonal antibodies generated by authentic human antigen, have been proven far superior in quality than traditional small peptide generated monoclonal and polyclonal antibodies, especially in applications such as flow cytomery and multiplex ELISA assays. Many of these monoclonal antibodies are currently available and will be utilized by multiple commercial partners for various applications.

About OriGene Technologies

OriGene Technologies, Inc., is a gene centric life sciences tool company dedicated to support academic, pharmaceutical and biotech companies in their research of gene functions and drug discovery.  OriGene’s novel product line includes the world’s largest cDNA and shRNA clone collections, over 5,000 purified human proteins, high quality monoclonal antibodies (TrueMABTM), 100,000 highly validated human tissues, and Luminex Multiplex Assay Products.  OriGene also provides a broad range of antibody validation products including genome-wide tagged antigen standards and extensive IHC slides derived from our tissue collection. OriGene is committed to its mission to be “Your Gene Company;” in supplying everything a researcher would need for gene based research.

R&D Investment by U.S. Biopharmaceutical Companies Remains Strong Despite Ongoing Economic Challengesph


Washington, D.C.  – Despite a fragile economy, America’s pharmaceutical research and biotechnology companies invested a record $65.3 billion last year in the research and development of new life-changing medicines and vaccines – an increase of more than $1.5 billion from 2008, according to analyses by the Pharmaceutical Research and Manufacturers of America (PhRMA) and Burrill & Company.

This investment reflects the continued commitment of America’s biopharmaceutical research companies to lead the world in the pursuit of new, life-saving and life-enhancing medicines. PhRMA-member companies alone spent an estimated $45.8 billion on pharmaceutical R&D last year, according to the PhRMA survey. The Burrill & Company analysis shows that non-PhRMA pharmaceutical research companies in the United States spent an estimated $19.5 billion on R&D in 2009.

Investment in R&D by America’s pharmaceutical research and biotechnology companies remained strong last year, in the face of a weak economic environment and historically low growth in drug spending. While companies have been forced to make difficult business decisions, research spending as a percentage of sales remained high in 2009. Over the past nine years, America’s pharmaceutical research companies have consistently invested around 18 percent of domestic sales on R&D activities.

“America’s biopharmaceutical research sector takes great pride in its global leadership in the development of new life-saving treatments and cures,” said PhRMA President and CEO Billy Tauzin. “Over the past year the economic challenges have been enormous, but our industry’s continued commitment to R&D is bringing hope to millions of patients around the world who are battling potentially devastating diseases such as cancer, heart disease and diabetes.”

U.S. biopharmaceutical companies’ focus on research has been observed by many independent experts. For instance, the nonpartisan Congressional Budget Office (CBO) has said: “The pharmaceutical industry is one of the most research-intensive industries in the United States. Pharmaceutical firms invest as much as five times more in research and development, relative to their sales, than the average U.S. manufacturing firm.”

Last year, University of Connecticut researchers similarly found that over the past 25 years, investment in R&D by the pharmaceutical and biotechnology sectors greatly exceeded that of all other industries in the U.S.

Importantly, this investment has produced results. According to a 2006 CBO analysis, “Many examples exist of major therapeutic gains achieved by the industry in recent years…. [A]necdotal and statistical evidence suggests that the rapid increases that have been observed in drug-related R&D spending have been accompanied by major therapeutic gains in available drug treatments.”

For instance, independent research shows that cancer patients are living, on average, three years longer – and 83 percent of those survival rate gains are due to new treatments, including medicines. Heart failure and heart attack deaths fell by nearly half from 1999 to 2005. And since the advent of highly active anti-retroviral therapy in 1995, the annual number of U.S. deaths due to AIDS has plummeted by more than 70 percent.

As in past years, an increasing number of potential new drugs are entering clinical testing. Today, there are more than 2,900 medicines in clinical trials or awaiting review by the Food and Drug Administration in the U.S., compared with 2,400 in 2005. The current pipeline includes more than 800 medicines to treat cancer, over 300 specific to rare diseases and more than 300 medicines for heart disease and stroke.

“This exciting research not only carries the potential to dramatically change and improve the lives of countless patients, it supports valuable and rewarding jobs for millions of American workers,” said Tauzin. “With unemployment rates remaining high, our nation must embrace strong sectors such as ours. If we want to maintain our leadership in biopharmaceutical R&D – and the subsequent value it brings to our state and national economies – it’s critical that the U.S. preserve policies that make such research possible.”

The Pharmaceutical Research and Manufacturers of America (PhRMA) represents the country’s leading pharmaceutical research and biotechnology companies, which are devoted to inventing medicines that allow patients to live longer, healthier, and more productive lives. PhRMA companies are leading the way in the search for new cures. PhRMA members alone invested an estimated $45.8 billion in 2009 in discovering and developing new medicines. Industry-wide research and investment reached a record $65.3 billion in 2009.

The fountain of youth is pregnancy


By JUDY SIEGEL-ITZKOVICH

Israeli researchers find pregnancy can be mimicked to regenerate tissue.

For the first time in the world, Jerusalem researchers have discovered that pregnancy has the remarkable ability to promote the regeneration in elderly mice of damaged livers and muscles. They have also managed to mimic the state of pregnancy using specific molecules that trigger the regeneration and growth of livers in older rodents.This basic new concept from Hadassah University Medical Center and the Hebrew University-Hadassah Medical School could eventually be relevant to other tissues and organs and lead to the ability to stimulate their regeneration in elderly, sick patients.

An article on the research by Dr. Yuval Gielchinsky, Prof. Neri Laufer, Prof. Yehudit Bergman and colleagues has just been published in the prestigious journal Genes & Development and aroused much interest among scientists.

Laufer, who is chairman of the department of obstetrics and gynecology at the medical center in Jerusalem’s Ein Kerem, told The Jerusalem Post on Wednesday evening that the research began soon after he read an article five years ago in the journal Nature.

The authors of that article had connected young mice to other young mice by uniting their blood vessels; old mice to old mice; and young mice to old mice (this procedure is called parabiosis).

If a mouse was either young or old and attached to a young mouse – and it suffered liver damage – the connection via blood circulation led to regeneration of tissue in the damaged organ. In aging rodents and elderly people, regeneration of the liver and other tissue is slow or even impossible.

Bergman, an expert in molecular immunology, developmental biology and gene expression at the medical school, told the Post: “One day about four years ago, a young gynecologist named Dr. Yuval Gielchinsky came into my office and said Neri suggested he come to me to do his Ph.D. and for me to be his supervisor.

“I asked if he knew what I do in my lab – epigenetics [the study of changes in the appearance or gene expression caused by mechanisms other than changes in the underlying DNA sequence]. He said he didn’t.

“We thought of all kinds of ideas, until Neri came and told us about the article in Nature. It seemed to him that pregnancy was a kind of parabiosis in which a mother is connected by blood vessels to its young fetus. Investigating this was appealing, and this is what Yuval set off to do.”

Also involved in the research was Dr. Eli Pikarsky of the medical school’s pathology department and Lautenberg Center for Immunology, as well as Efi Weitman, Dr. Rinat Abramovitch and Dr. Zvi Granot.

The team studied mice and indeed found that damage to tissue in the foot muscle (and later liver) of an older but pregnant mouse was quickly repaired, as if it had been connected to a live young animal. The researchers knew there was something in the blood that was doing this, but couldn’t explain what it was and how it worked.

Laufer said that when a young animal loses two-thirds of its liver, it can regenerate the lost tissue in a few days. But if it is old, half of the mice would die due to stress on the organ. Of those that survive, much less tissue would be regenerated.

But if the mouse is older and pregnant, its tissue regenerates as if it were young.

The regenerative capacity of tissue declines with age, and healing in response to injury is delayed, he said. This effect is observed in liver, skin, bones, blood vessels, nerves, muscles and other tissue. The reason is that ageing alters the function of many biological processes such as changes in growth factors, the accumulation of damage to DNA in the cells and the increase in oxygen free radicals in the cells.

They learned that the repair mechanism was a kind of switch within the cells, and that it can be made to work with specific molecules (drugs) to stimulate and repair them.

The significance of this, explained Laufer, “is that part of the liver can be removed from old animals, they can be given drugs and this will cause the remaining liver to regenerate as if they were pregnant but without actually being pregnant.”

The new research shows that pregnancy causes a switch from regeneration based on proliferation (an increase in the number of cells due to cell division) to regeneration caused by hypertrophy (the increase in the volume of an organ or tissue due to the enlargement of its component cells). Certain molecules given to aged mice induced hypertrophy in their livers, thus mimicking the state of pregnancy and lengthening their lifespan.

The fountain of youth, he said, “is pregnancy. That is the new concept we developed. It has rejuvenating ability.

“But the advantages of pregnancy can be produced in non-pregnant animals. We are now working to see if this affects their longevity. If this concept can be transferred to humans, it could allow people to recover from illness or disease naturally and more quickly and weaken the effects of old age.”

Bergman said they first worked on muscle tissue but then switched to the liver, as it is already a very well-studied organ model. In the future, the team will work on skin and other tissues.

“It was very surprising to see how pregnancy affects the regeneration of the liver,” she said.

The team has already received a preliminary patent – registered through Hadasit (the Hadassah Medical Organization’s technology transfer company) and Yissum (that of HU) – for the development of medication based on their findings.

The researchers concluded that it’s possible that similar means could be used to enhance the ability of the liver to regenerate in old people. Such advances could have considerable impact on those who are eligible for and/or in need of liver surgery, yet are at significant risk of surgical complications.

Roche aiming to launch 6 new products by end 2014


Swiss pharmaceutical company Roche CEO Severin Schwan addresses media as he attends the company’s annual news conference in Basel February 3, 2010.

(Reuters) – Roche Holding AG is aiming to launch at least six new products by the end of 2014 and is seeking to further boost its position in areas outside oncology, the Swiss drugmaker said ahead of its investor day. Health Roche, the world’s largest maker of cancer drugs, is aiming to build up its strength in the therapeutic areas of metabolism, inflammation and diseases of the central nervous system (CNS) as it tries to expand its product portfolio. Investors are looking to the group for reassurance about its pipeline strength after a number of setbacks and after its cancer drug sales fell short of expectations for last year. At 1008 GMT (6:08 a.m. ET), Roche stock was trading 0.7 percent higher at 174.90, largely in line with a stronger STOXX European healthcare sector index.

CANCER MEDICINES KEY

Roche said cancer drugs Avastin, MabThera and Herceptin, as well as arthritis medicine Actemra would drive short-term growth, adding in slides that it may file 35 line extensions of existing products, including blockbuster Avastin, by 2014. “Roche will focus on its diversification strategy to increase revenues in non-oncology such as metabolic disorders and CNS,” Vontobel analyst Silvia Schanz said. “However the oncology pipeline remains an important contributor with the BRAF drug in melanoma and pertuzumab in breast cancer to be a topic,” she said. Roche still expects Avastin, which slipped at recent hurdles in gastric and prostate cancer, could reach peak sales of between 8 billion and 9 billion Swiss francs ($7.56 billion and $8.51 billion). Many analysts believe it could be the world’s biggest-selling drug in a few years time. Avastin, which works by starving tumors of blood, is a flagship for Roche, given its potential to treat new types of cancer, and is already approved to treat colorectal, breast, kidney and lung cancer. “Avastin remains a major source of Roche’s growth despite having been on the market since 2004 and despite recent failures in prostate cancer and gastric cancer,” analysts at Bernstein said in a note. “In our forecasts, it accounts for around a quarter of Roche’s growth between now and 2015. The forecast growth comes mainly from ovarian and breast cancer indications, with a little help from geographic catch up,” they said. In an interview with Reuters on Wednesday, Chief Executive Severin Schwan said Roche’s experimental drugs to treat melanoma and raise “good” HDL cholesterol could transform treatment of cancer and heart disease. ($1=1.058 Swiss Franc) (Editing by Hans Peters and Rupert Winchester)

Support Network Seeks to Grow Biotech Companies


By JON VAN

Dr. Boris Pasche had worked for years with a battery-operated device to treat insomnia, but as he followed his

Dan Benier, left, and Thomas L. Flynn III of Therapeutic Proteins Inc., which is opening a manufacturing plant in Chicago.

research, he discovered that electromagnetic radiation from the apparatus might slow or stop tumor growth in some cancer patients, and he thought he could perhaps build a business around the idea.

Like most other academic researchers, Dr. Pasche knows little about starting a business or courting investors, but he is getting help for the Chicago-based biotechnology company he founded, TheraBionic.

The small-business development office at Northwestern University, where Dr. Pasche was affiliated, referred him to the Illinois biotechnology trade organization, iBIO, which linked him to local biotechnology volunteers offering guidance. They advised him on possible investors and coached him on making his pitch.

“I submitted a grant proposal to the National Institutes of Health, as this is a novel, potentially transformational, technology,” Dr. Pasche said. “This is my baby. I’d really like to see it succeed.”

TheraBionic is the sort of risky but high-potential company that might be a candidate for money under a federal program to promote commercial medical breakthroughs.

Universities and laboratories in the Chicago area have long been a source of innovations in the life sciences, but for decades inventors and entrepreneurs have often lacked the money and business savvy to bring their ideas to market. The story of TheraBionic and dozens of similar start-ups over the past few years indicates the serious effort to raise Chicago’s standing as a commercial biotech center.

The main obstacle that start-ups face is the absence of a critical mass of daring investors like those who fuel biotechnology development on the coasts, said Michael Rosen, senior vice president for Forest City Enterprises and the Illinois Science + Technology Park in Skokie.

“The problem is very few early-stage capital investment funds,” Mr. Rosen said.

What the area does have are drug and medical products companies like Abbott Laboratories and Baxter International and the North American headquarters of such major players as Takeda and

An assistant testing proteins at Therapeutic Proteins.

Astellas, Japan’s top two pharmaceutical companies. In recent years, executives at those companies have begun helping fledgling entrepreneurs with the managerial, legal and other business expertise they need to commercialize their research.

The turnaround started at a trade show of BIO, the world’s largest biotechnology organization. Chicago hosted the international BIO show in 2006, the first time the event was held outside the biotech centers on the East and West Coasts. The event attracted 20,000 participants, a record, and the process of organizing it helped bring together the area’s often diffuse biotechnology community.

It began to focus on supporting struggling newcomers and raising their profile nationally.

“We learned a lot of people who attended the convention didn’t know much about Chicago at all,” said Dr. Norbert Riedl, Baxter’s chief scientific officer and corporate vice president. “They didn’t know Baxter was here, Abbott, Takeda, Astellas — and world-class universities were here. It was clear we had to do more to promote those aspects of Chicago.”

Among the accomplishments after the trade show was a statewide program called Propel, modeled after an effort that helped turn San Diego into a biotechnology powerhouse.

“Propel is to train and educate entrepreneurs, to take innovation out of academic centers and place it into tech parks and allow it to flourish,” Dr. Riedel said.

Therapeutic Proteins Inc., a Deerfield company that is opening a manufacturing plant on Chicago’s South Side this spring, is one of the small local companies benefiting from Propel’s efforts. It plans to add 30 employees to the 6 it has now when operations begin at the new plant, said Thomas L. Flynn III, its chief executive. The company will make proteins used in generic biologic therapies that regulate blood sugar, produce blood cells and stimulate the immune system.

Propel helped Mr. Flynn by identifying contractors who could build specialized manufacturing facilities, locating a site within a technology park and steering him toward loan and grant programs that would enable his company to hire new employees. The company settled at the tech park at the Illinois Institute of Technology, where it constructed a 12,000-square-foot production plant.

While iBio, Propel and other efforts have built a sense of momentum among business people and others in the state, the timing has proven to be a challenge. Total venture investment in biotechnology in the state had reached $100 million a year in 2006 and 2007, according to the Illinois Venture Capital Association, but the amount fell over the last two years to around $40 million, as the recession and tight credit markets caused a pullback on all venture investment.

Biotechnology’s share of total venture investment hit a low of 8 percent in 2008, but climbed to 21 percent last year, close to the level in 2006, the year the trade show was in Chicago.

“This suggests the resilience of biotech in Illinois,” said Maura O’Hara, executive director of the Illinois Venture Capital Association. “Bouncing back to get about one-fifth of the state’s venture investment is an accomplishment.”

Another iBIO gathering is scheduled for McCormick Place in May, and Mr. Flynn hopes to use it to show off his company’s capabilities to buyers from around the world. The show promotes such deal-making by, among other things, arranging computerized match-ups between vendors and potential customers.

In the past few years, Propel has helped about 50 companies file for patents on their technology and secure increased financing, said David Miller, executive director of iBIO. Several have advanced enough to expand their work force, he said

Still, Mr. Miller said, Illinois has not seen its biotech start-up companies prosper as much as those based in Wisconsin, Ohio and Michigan. iBIO plans to change Propel’s legal status to that of a philanthropic entity that can receive federal grants and foundation money, something a trade organization like iBIO cannot do.

Mr. Miller’s organization is also seeking state legislation to provide tax breaks to those who invest in early-stage start-up companies. Twenty-five other states have such tax breaks, he said, and most have seen a marked increase in new technology companies.

Getting Illinois lawmakers to pass a tax break at a time when the state is desperate for more revenue may be difficult, though Mr. Miller said that iBIO’s proposed legislation passed the Senate last year with no opposition and that this year a quarter of the membership of the House had agreed to sponsor the measure.

Providing tax breaks to early-stage investors “would be a good step in the right direction,” said Thomas Churchwell, managing partner of Chicago-based Midwest Venture Partners. Early-stage investors, or “angels,” help start-up companies stay in business through a period known as “the valley of death” when development costs are high and clinical trials must be conducted. Venture capitalists typically come in when the product is nearly ready for market.

“You start with angel funding and some combination of venture capital and corporate strategic relationships,” Mr. Churchwell said. “It takes so much money to get a company off the ground, it’s unlikely that angels alone will get you there.”

Hosting the iBIO show in 2006 was significant in lifting confidence among Midwestern biotech players, Mr. Churchwell said, and the May gathering will represent a kind of progress report for the community.

“As time goes on, folks are going to prove this is going to work,” he said. “You have to convince yourself it can happen, and it does.”

Dopamine levels in brain 'influence decision making'


Dopamine, a chemical with a key role in setting people’s moods, could have a much wider-ranging impact on their everyday lives, research suggests.

Human brain

Dopamine is known to have a “reward” function in the brain

Experiments show that altering levels of the chemical in the brain influences the decisions people make.

One expert said the results showed the relative importance of “gut feeling” over analytical decision making.

The Current Biology study could help understand how expectation of pleasure can go awry, for example in addiction.

It follows previous research by the University College London team, which, using imaging techniques, detected a signal in the brain linked to how much someone enjoyed an experience. They found that signal could in turn predict the choices a person made.

With the suspicion that the signal was dopamine, the researchers set up a study to test how people make complex decisions when their dopamine system has been tampered with.

The 61 participants were given a list of 80 holiday destinations, from Greece to Thailand, and asked to rate them on a scale of one to six.

Dopamine has a role in signalling the expected pleasure from those possible future events
Tali Sharot
Wellcome Trust Centre for Neuro-imaging

They were then given a sugar pill and asked to imagine themselves in each of 40 of the destinations.

Researchers then administered L-Dopa, a drug used in Parkinson’s disease to increase dopamine concentrations in the brain, before asking them to imagine the other holidays.

They rated all the destinations again, and a day later they were asked where they would prefer to go, out of paired lists of holidays.

The extra dopamine gave people higher expectations when rating holiday options.

And that translated into the choice of trip they made a day later.

Study leader Dr Tali Sharot, from the Wellcome Trust Centre for Neuro-imaging at UCL, said humans made far more complex decisions than other animals, such as what job to take and whether to start a family, and it seemed dopamine played an important part in that.

It is a sort of shortcut in our thinking
Professor John Maule
Leeds University

She said they had been surprised at the strength of the effect they had seen.

“Our results indicate that when we consider alternative options when making real-life decisions, dopamine has a role in signalling the expected pleasure from those possible future events.

“We then use that signal to make our choices.”

Dr Sharot added that addicts overestimated the pleasure they would gain from something, be it heroin or gambling, because their dopamine system was dysfunctional, and the latest research underpinned that the choices they made would be influenced by that.

Gut instinct

She added: “For many conditions we have medication which changes dopamine function, so knowing we may be changing people’s expectations and their decision making might change how we think about giving these types of medications.”

Professor John Maule, an expert in decision making, at Leeds University Business School, said that in recent years people had begun to realise emotional or “gut instinct” decision making was just as important in human choices as analytical decision making.

“At any one time you will have both these processes going on, so it’s not surprising to see these results, especially when it comes to emotionally based decisions, such as holidays.

“It is a sort of shortcut in our thinking.”

Report: Life sciences firms amass venture funding worth $1.9B in Q4


U.S. life sciences companies secured $1.9 billion in venture capital funding in the fourth quarter, led by the $55

Todd Pope, president and CEO of TransEnterix.

million second-round haul of Durham medical device company TransEnterix, according to a report released Monday by online venture capital database VentureDeal.

The $1.9 billion represents almost no change compared to the third quarter and continues a stable trend of funding for companies in the biotechnology, pharmaceutical and medical-devices fields.

Biotechnology received the most money, $871 million among 69 companies. Medical devices followed with 78 companies raising $572 million in the quarter. Forty-five pharmaceutical companies raised $460 million.

TransEnterix, which has raised a total of $76 million in venture-capital financing and has said it would hire 50 employees this year, is working to commercialize technology that permits a less invasive surgery requiring a single incision in the abdomen compared with the four to five incisions currently required.

Brain scans ‘can distinguish memories’, say scientists


brain scan

Brain scans revealed which event a person was rememberi

Scientists say they have been able to tell which past event a person is recalling using a brain scan.

The University College London researchers showed people film clips and were able to predict which ones they were subsequently thinking about.

The research, published in Current Biology, provides insight into how memories are recorded.

The authors hope the findings will ultimately contribute to development of treatments for memory loss.

Previous research has shown brain scans can predict simpler thought processes such as distinguishing between colours, objects or places.

The UCL researchers say recalling memories of past events is a more complex process.

Everyday memories

The study builds on a previous discovery by the same team that they could tell where a person was standing in a virtual reality room using a brain scan.

“In our previous experiment, we were looking at basic memories, at someone’s location in an environment,” says Professor Maguire, from the Wellcome Trust Centre for Neuroimaging at UCL, who led the study.

“What is more interesting is to look at ‘episodic’ memories – the complex, everyday memories that include much more information on where we are, what we are doing and how we feel.”

Now that we are developing a clearer picture of how our memories are stored, we hope to examine how they are affected by time, the ageing process and by brain injury
Professor Eleanor Maguire, UCL

The researchers asked 10 volunteers to watch three short film clips of people doing everyday activities such a posting a letter or throwing a coffee cup in a bin.

The volunteers were then asked to remember each of the films in turn while inside a specialist MRI scanner, which recorded brain activity that was then studied by a computer programme.

First time

The researchers found that in subsequent scanning sessions, the computer algorithm could predict which film the volunteers were thinking about from the pattern of their brain activity.

They said it was the first time that brain scans had been used to distinguish between memories of past events.

Experts praised the research. Richard Morris, professor of neuroscience at the University of Edinburgh, said: “These findings are a really valuable advance on traditional ways of analysing brain images. They look not just at the strength of the signal, but the actual pattern of activity across the brain.

“By doing this in memory areas, it is possible for the first time to distinguish one memory from another – even if both memories are equally strong.”

The computer algorithm doesn’t really ‘read’ memories – it merely distinguishes one from another.
Professor Richard Morris, Glasgow University

But he pointed out that the research does not mean it is possible to literally know what a person is remembering.

“The computer algorithm doesn’t really ‘read’ memories – it merely distinguishes one from another.”

He said the findings could lead to a whole range of interesting developments.

“All manner of next steps come to mind – such as distinguishing a true memory from a false one, or a recent memory from one long ago.”

The scientists say their research contributes to an understanding of how memories are formed and recalled. They hope it will eventually help develop treatments for people with memory loss though ageing or brain injury.

Dr Susanne Sorensen, Alzheimer’s Society’s head of research said: “This research is interesting because it tells us more about how memories are stored and recalled in normal healthy people.

“It is not directly related to the study of the memory problems that are one of the symptoms of dementia, but the methods developed in this study may in the longer term help us investigate what goes wrong in brains that are developing the diseases which cause dementia.”

Merck and Portola: Finding a Blood Thinner’s Sweet Spot


By Ron Winslow

heart“In evaluating an anticoagulant,” says heart researcher Michael Ezekowitz, “it’s all about getting the dose right.”

That’s the next big challenge for Merck and its partner Portola as they prepare to advance the closely held South San Francisco biotech’s drug betrixaban into a large-scale clinical trial in the burgeoning race to develop a replacement for the heart drug warfarin.

Ezekowitz, a cardiologist at Lankenau Institute for Medical Research, Wynnewood, Pa., told a packed auditorium at the annual science meeting of the American College of Cardiology on Monday that a daily 40-milligram dose of betrixaban caused significantly fewer cases of major or clinically important bleeding than standard treatment with warfarin. Bleeding rates were simliar warfarin at 60 and 80 milligrams, said Ezekowitz, who led  the study. Side affects included diarrhea and nausea.

The Phase 2 study tested the medicine in patients with atrial fibrillation, a heart rhythm disorder that afflicts some 2.5 million Americans and carries the risk of blood clots that can lead to a stroke.

Warfarin, a half-century old workhorse anticoagulant from Bristol-Myers Squibb and generic companies, effectively prevents such clots. But patients need regular blood checks and frequent dose changes to prevent life-threatening clots or bleeding episodes.

After decades of frustration in the hunt for an effective alternative that doesn’t require monitoring, the pipeline is now full of promise. Boehringer Ingleheim, Daiichi Sankyo and joint ventures between Pfizer and Bristol-Myers and Johnson & Johnson and Bayer all have compounds in development for a global market that some analysts expect will exceed $10 billion by later in the decade.

Merck and Portola trail most of their rivals at the moment, but they believe features of its compound, including once-daily dosing and the fact that Portola is developing an antitode that could quickly turn the drug off in the event of a dangerous bleed, could be advantages for betrixaban if it reaches the market.

First they have to find the dose that hits the sweet spot between too much clotting and too much bleeding. Will a 40-milligram dose with the favorable bleeding risk be strong enough to effectively prevent clots? That’s one big question Merck and Portola will ponder in the months ahead as they plan a trial they hope will lead to the drug’s approval.

Bill Lis, Portola’s new CEO, indicated one possibility is to move more than one dose into a Phase 3 trial. “It’s clear we have an active drug that is safe and tolerable and ready for the next stage of development,” Lis says.

wsj.com

ProteoLogics IPO oversubscribed three-fold


In response, ProteoLogics raised the price of units of shares and warrants by 23%.
Gali Weinreb
 Proteologics
Proteologics Ltd. marked up an extraordinary success in its IPO on the Tel Aviv Stock Exchange (TASE) yesterday. The public offering was oversubscribed nearly three-fold, with NIS 100 million in orders for the units of shares and warrants, compared with the NIS 35 million that the company planned to raise.In response, ProteoLogics raised the price of units by 23% to give a company value of NIS 147 million, after money. Clal Finance Underwriting Ltd. led the IPO, together with Meitav Issuing And Finance Ltd., Menora Mivtachim Underwriters & Management Ltd., Leumi Partners Ltd., and Barak Capital Underwriting Ltd.The success of the offering will bring into effect ProteoLogics’ investment agreement with GlaxosmithKline plc (NYSE; LSE: GSK), which will immediately invest $3 million in the company and make an additional $2 million payment to finance R&D. GlaxosmithKline is due to invest an additional $3.4 million in ProteoLogics over the coming years. The total investment could reach as much as $1 billion.Two key factors played a role in the IPO’s success: ProteoLogics’ cooperation agreement with GlaxosmithKline, announced last week; and the general strong interest in Israeli biomedical companies in recent weeks.Five biomedical companies have carried out or plan to carry out reverse merges with stock market shells, the TASE launched its Biomed Index yesterday to great acclaim, and there is a general appetite among investors for risk whetted by the market rally and the gushing oil exploration partnerships.

A source who participated in ProteoLogics’ IPO said, “Even the underwriters were in shock by the demand.”

Published by Globes [online], Israel business news – www.globes-online.com – on March 3, 2010

© Copyright of Globes Publisher Itonut (1983) Ltd. 2010

ProteoLogics IPO oversubscribed three-fold
In response, ProteoLogics raised the price of units of shares and warrants by 23%.
Gali Weinreb 3 Mar 10 12:45
Proteologics Ltd. marked up an extraordinary success in its IPO on the Tel Aviv Stock Exchange (TASE) yesterday. The public offering was oversubscribed nearly three-fold, with NIS 100 million in orders for the units of shares and warrants, compared with the NIS 35 million that the company planned to raise.In response, ProteoLogics raised the price of units by 23% to give a company value of NIS 147 million, after money. Clal Finance Underwriting Ltd. led the IPO, together with Meitav Issuing And Finance Ltd., Menora Mivtachim Underwriters & Management Ltd., Leumi Partners Ltd., and Barak Capital Underwriting Ltd.The success of the offering will bring into effect ProteoLogics’ investment agreement with GlaxosmithKline plc (NYSE; LSE: GSK), which will immediately invest $3 million in the company and make an additional $2 million payment to finance R&D. GlaxosmithKline is due to invest an additional $3.4 million in ProteoLogics over the coming years. The total investment could reach as much as $1 billion.Two key factors played a role in the IPO’s success: ProteoLogics’ cooperation agreement with GlaxosmithKline, announced last week; and the general strong interest in Israeli biomedical companies in recent weeks.Five biomedical companies have carried out or plan to carry out reverse merges with stock market shells, the TASE launched its Biomed Index yesterday to great acclaim, and there is a general appetite among investors for risk whetted by the market rally and the gushing oil exploration partnerships.

A source who participated in ProteoLogics’ IPO said, “Even the underwriters were in shock by the demand.”

Published by Globes [online], Israel business news – www.globes-online.com – on March 3, 2010

© Copyright of Globes Publisher Itonut (1983) Ltd. 2010

Even More Reasons to Get a Move On


By JANE E. BRODY

“I’m 86 and have walked every day of my life. The public needs to wake up and move.”

“I’m 83 going on 84 years! I find that daily aerobics and walking are fine. But these regimens neglect the rest of the body, and I find the older you get the more attention they need.”

These are two of many comments from readers of my Jan. 12 column on the secrets of successful aging. At the risk of sounding like a broken record, a new series of studies prompts me to again review the myriad benefits to body, mind and longevity of regular physical activity for people of all ages.

Regular exercise is the only well-established fountain of youth, and it’s free. What, I’d like to know, will persuade the majority of Americans who remain sedentary to get off their duffs and give their bodies the workout they deserve? My hope is that every new testimonial to the value of exercise will win a few more converts until everyone is doing it.

In a commentary on the new studies, published Jan. 25 in The Archives of Internal Medicine, two geriatricians, Dr. Marco Pahor of the University of Florida and Dr. Jeff Williamson of Winston-Salem, N.C., pointed to “the power of higher levels of physical activity to aid in the prevention of late-life disability owing to either cognitive impairment or physical impairment, separately or together.”

“Physical inactivity,” they wrote, “is one of the strongest predictors of unsuccessful aging for older adults and is perhaps the root cause of many unnecessary and premature admissions to long-term care.”

They noted that it had long been “well established that higher quantities of physical activity have beneficial effects on numerous age-related conditions such as osteoarthritis, falls and hip fracture, cardiovascular disease, respiratory diseases, cancer, diabetes mellitus, osteoporosis, low fitness and obesity, and decreased functional capacity.”

One of the new studies adds mental deterioration, with exercise producing “a significantly reduced risk of cognitive impairment after two years for participants with moderate or high physical activity” who were older than 55 when the study began.

Most early studies demonstrating the benefits of exercise were done with men. Now a raft of recent studies has shown that active women reap comparable rewards.

Research-Based Evidence

Sedentary skeptics are fond of saying that of course exercise is associated with good health as one ages; the people who exercise are healthy to begin with. But studies in which some participants are randomly assigned to a physical activity program and others to a placebo (like simply being advised to exercise) call their bluff. Even less exacting observational studies, like the Nurses’ Health Study, take into account the well-being of participants at enrollment.

Thus, in one of the new studies, Dr. Qi Sun of Harvard School of Public Health and co-authors reported that among the 13,535 nurses who were healthy when they joined the study in 1986, those who reported higher levels of activity in midlife were far more likely to still be healthy a decade or more later at age 70. The study found that physical activity increased the nurses’ chances of remaining healthy regardless of body weight, although those who were both lean and active had “the highest odds of successful survival.”

Taking the benefits of exercise one system at a time, here is what recent studies have shown, including several published in The Archives of Internal Medicine in December.

Cancer. In a review last year of 52 studies of exercise and colon cancer, researchers at Washington University School of Medicine in St. Louis concluded that people who were most active were 21 percent less likely to develop the disease than those who were least active, possibly because activity helps to move waste more quickly through the bowel.

The risk of breast cancer, too, is about 16 percent lower among physically active women, perhaps because exercise reduces tissue exposure to insulin-like growth factor, a known cancer promoter.

Indirectly, exercise may protect postmenopausal women against cancers of the endometrium, pancreas, colon and esophagus, as well as breast cancer, by helping them keep their weight down.

Osteoporosis and fragility. Weak bones and muscles increase the risk of falls and fractures and an inability to perform the tasks of daily life. Weight-bearing aerobic activities like brisk walking and weight training to increase muscle strength can reduce or even reverse bone loss. In one of the new studies, German researchers who randomly assigned women 65 and older to either an 18-month exercise regimen or a wellness program demonstrated that exercise significantly increased bone density and reduced the risk of falls. And at any age, even in people over 100, weight training improves the size and quality of muscles, thus increasing the ability to function independently.

Cardiovascular disease. Aerobic exercise has long been established as an invaluable protector of the heart and blood vessels. It increases the heart’s ability to work hard, lowers blood pressure and raises blood levels of HDL-cholesterol, which acts as a cleansing agent in arteries. As a result, active individuals of all ages have lower rates of heart attacks and strokes.

Though early studies were conducted only among men, in a 2002 study published in The New England Journal of Medicine, Dr. JoAnn E. Manson and colleagues found that among 73,743 initially healthy women ages 50 to 79, walking briskly for 30 minutes a day five days a week, as well as more vigorous exercise, substantially reduced the risk of heart attacks and other cardiovascular events.

In another study, women who walked at least one hour a day were 40 percent less likely to suffer a stroke than women who walked less than an hour a week.

Diabetes. Moderate activity has been shown to lower the risk of developing diabetes even in women of normal weight. A 16-year study of 68,907 initially healthy female nurses found that those who were sedentary had twice the risk of developing diabetes, and those who were both sedentary and obese had 16 times the risk when compared with normal-weight women who were active.

Another study that randomly assigned 3,234 prediabetic men and women to modest physical activity (at least 150 minutes a week) found exercise to be more effective than the drug metformin at preventing full-blown diabetes.

Dementia. As the population continues to age, perhaps the greatest health benefit of regular physical activity will turn out to be its ability to prevent or delay the loss of cognitive functions. The new study of 3,485 healthy men and women older than 55 found that those who were physically active three or more times a week were least likely to become cognitively impaired.

One study conducted in Australia and published in September 2008 in The Journal of the American Medical Association randomly assigned 170 volunteers who reported memory problems to a six-month program of physical activity or health education. A year and a half later, the exercise group showed “a modest improvement in cognition.” Various other studies have confirmed the value of exercise in helping older people maintain useful short-term memory, enabling them to plan, schedule and multitask, as well as store information and use it effectively.

Hopes for Alzheimer’s Drug Are Dashed


By ANDREW POLLACK

John Eckert holds hands with wife Dorothy, who has Alzheimer’s disease, at their home in Norristown, Pa. (NYT.com)

It seemed somewhat unlikely, but in recent years an old Russian hay fever pill had become one of the world’s best hopes for treating the growing epidemic of Alzheimer’s disease.

But those hopes were dashed on Wednesday when the drug failed in its first late-stage clinical trial, dealing a blow not only to patients with Alzheimer’s and their families but to the companies developing the treatment — a start-up in San Francisco called Medivation and the world’s largest drug company, Pfizer.

The companies said in a statement that the drug, called Dimebon, had shown virtually no effect after six months in treating the cognitive decline or behavioral problems associated with Alzheimer’s when compared with a placebo.

The result was somewhat surprising, because in a smaller previous trial, Dimebon had shown what some experts characterized as better results than any of the drugs already approved for Alzheimer’s disease. It seemed to improve cognitive function or at least stave off mental decline for about 18 months, while the existing treatments do so for only about six months, experts said.

As recently as last week, an Alzheimer’s researcher had said of Dimebon, “The clinical data is by far and away superior to anything that’s ever been shown before.”

That researcher, Mark A. Smith, of Case Western Reserve University, is a consultant to Medivation who is trying to figure out how the drug works.

Still, some doctors and Wall Street investors had been a bit skeptical, because that earlier trial had been done in Russia, making it hard to determine how the study was conducted. Also, the mechanism by which Dimebon worked was never clear.

“It just seemed too good to believe,” Dr. John Q. Trojanowski, director of the Alzheimer’s center at the University of Pennsylvania, said in an interview Wednesday.

The skeptics were borne out by the results of the new trial, called Connection, which involved 598 patients with mild to moderate Alzheimer’s disease in Europe and in North and South America.

“The outcome for the Connection trial was unexpected,” Dr. David Hung, the chief executive of Medivation, told securities analysts in a conference call Wednesday. “With this data we have to reconsider the entire program.”

Shares of Medivation lost two-thirds of their value Wednesday, plummeting to $13.10.

Before the results were announced, Medivation, which has no products on the market, had a market valuation of $1.3 billion based largely on the prospects for Dimebon.

The big questions now are whether the companies abandon other trials already under way for Dimebon or whether Pfizer itself, which has been paying 60 percent of the development costs, pulls out.

Executives at both companies said they needed to further analyze the results before making such decisions.

Dimebon, also known as latrepirdine, was sold as an antihistamine in Russia starting around 1983, though production and sales of the drug had stopped some years ago.

In the 1990s, Sergey Bachurin, a scientist at the Institute of Physiologically Active Compounds in Russia, had started screening chemicals that might be used to treat Alzheimer’s. He discovered that the already approved antihistamine seemed to fit the bill. The researchers tested the drug in animals and in a small group of patients, then filed for patents.

Sergey Sablin, a former researcher at the Russian institute who moved to San Francisco, shopped around for American investors to develop the drug. He met Dr. Hung, who had already succeeded with a previous company, and Medivation was set up.

Medivation in turn licensed rights to Dimebon to Pfizer for a large initial payment of $225 million. Pfizer already sells Aricept, a leading drug for Alzheimer’s, but that product will be losing patent protection later this year.

Shares of Pfizer fell 28 cents, or about 1.6 percent, to $17.32.

Medivation and Pfizer are conducting additional trials in which Dimebon is being combined with other Alzheimer’s drugs.

U.S. FDA approves Labopharm antidepressant


FDA approves once-daily trazodone antidepressant

Labopharm_200* Company seeking partnership for drug

* U.S. antidepressant market valued at $11 bln

* Shares up more than 15 pct in premarket trading (Adds company comments; in U.S. dollars unless noted)

The U.S. Food and Drug Administration has approved a once-daily antidepressant made by Labopharm Inc (DDS.TO), the Canadian company said, sending its shares up more than 15 percent in premarket trading.

The approval clears the way for the biotechnology company to launch the drug, trazodone, on the U.S. market later this year.

Labopharm President and Chief Executive James Howard-Tripp said the timing of the launch was contingent on the Montreal-based company finding a partner for the drug.

Howard-Tripp said Labopharm was studying several commercialization options for trazodone, including licensing the drug to another company or a co-promotion deal.

Although Howard-Tripp said Labopharm was in discussions with an “international” company concerning partnering, he refused to commit to a timeframe.

“We prefer to go down the co-promotion route where we will have more of a role (in the development),” he told Reuters. “This gives us a much higher degree of control of our own asset, and the financial return is significantly better.”

Some 14 million adults in the United States suffer from major depression. The U.S. market for antidepressants is valued at more than $11 billion.

Howard-Tripp declined to set a yearly U.S. sales figure for the treatment, but TD Newcrest analyst Lennox Gibbs said in a recent report that if it fails to clear the $20 million threshold this year it would be an early indication that the launch was faltering.

Approval of the drug was stalled last year after the FDA raised concerns about the manufacturing process at an Italian plant that produced the drug’s active ingredient.

Labopharm has also filed an application for approval with Canadian regulators and expects a decision sometime in August.

The U.S. approval of trazodone is the second approval for the company in less than a year. Last year it received approval for its tramadol-acetaminophen combination pain treatment. ($1=$1.06 Canadian) (Reporting by Scott Anderson; editing by John Wallace)

APEIRON AND GSK SIGN AN EXCLUSIVE LICENSE AGREEMENT FOR APEIRON’S THERAPEUTIC ENZYME PROJECT APN01


Apeiron Biologics AG (Apeiron) today announced the signing of an agreement granting GlaxoSmithKline (GSK) exclusive rights to APN01 (recombinant human Angiotensin Converting Enzyme 2, rhACE2), an enzyme biotherapeutic currently in Phase 1 development for the treatment of the Acute Respiratory Distress Syndrome (ARDS).

Under the terms of the agreement, the total milestone payments could reach £ 207 million (approx. EUR 239 million) in the event of launch in multiple indications. Apeiron will receive an up-front payment of £ 11 million (approx. EUR 12.7 million) in cash and equity

GSK

investment and will receive royalties on net sales.

Commenting on the agreement, the founder of Apeiron, renowned scientist Josef Penninger, stated: “When I returned to Austria after several years of basic research in North America, I had the vision of translating some of my research, including that for ACE2, into clinically useful and commercially viable products. For this purpose I founded Apeiron and was able to attract excellent management. I am impressed to see how quickly and successfully the basic idea was translated into a clinical project with such promising perspectives. GSK is a most welcome partner for further development.”

Hans Loibner, CEO of Apeiron, added: “We are very pleased that we could attract GSK, one of the world’s top pharmaceutical companies, to license this exciting project. I am convinced that Apeiron’s know-how in this area, together with the extensive development and marketing capabilities of GSK, are the best way forward to bring an innovative therapy to patients worldwide.”

Manfred Reichl, Chairman of the Supervisory Board and business angel, stated: “Remarkably, Apeiron achieved this major success without prior Venture Capital financing, but only with individual private investors. This proves that the Biotech cluster in Vienna has come a long way and is catching up to global standards in research quality, management capabilities and financing.”

About ARDS:

Acute Respiratory Distress Syndrome (ARDS) is an acute, severe injury to the lungs associated with a variety of conditions, such as sepsis, aspiration of acidic gastric contents, trauma, postoperative complications, acute pancreatitis, and pneumonias e.g. due to infections with human influenza viruses. According to recent analyses, it affects millions of individuals worldwide/year (up to one million in OECD countries alone). ARDS has a mortality rate of 30-50% and, up to date, no effective drugs exist to treat this life-threatening condition.

About Apeiron:

Apeiron Biologics AG is a privately financed biotech company in Vienna, Austria, founded by Josef Penninger, Director of the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA). As its main project Apeiron has developed recombinant human Angiotensin Converting Enzyme 2 (rhACE2; project name: APN01) as biotherapeutic up to Phase I clinical trials. Target indications for APN01 are diseases with an imbalance of the Renin Angiotensin System and insufficient natural ACE2 activity.

Special focus was devoted to explore the therapeutic potential of rhACE2 for the treatment of ARDS. In addition to its activities for APN01, Apeiron pursues two additional projects in preclinical development, also stemming from research activities of Josef Penninger.

Apeiron Biologics AG (Apeiron) today announced the signing of an agreement granting GlaxoSmithKline (GSK) exclusive rights to APN01 (recombinant human Angiotensin Converting Enzyme 2, rhACE2), an enzyme biotherapeutic currently in Phase 1 development for the treatment of the Acute Respiratory Distress Syndrome (ARDS).

Under the terms of the agreement, the total milestone payments could reach £ 207 million (approx. EUR 239 million) in the event of launch in multiple indications. Apeiron will receive an up-front payment of £ 11 million (approx. EUR 12.7 million) in cash and equity investment and will receive royalties on net sales.

Commenting on the agreement, the founder of Apeiron, renowned scientist Josef Penninger, stated: “When I returned to Austria after several years of basic research in North America, I had the vision of translating some of my research, including that for ACE2, into clinically useful and commercially viable products. For this purpose I founded Apeiron and was able to attract excellent management. I am impressed to see how quickly and successfully the basic idea was translated into a clinical project with such promising perspectives. GSK is a most welcome partner for further development.”

Hans Loibner, CEO of Apeiron, added: “We are very pleased that we could attract GSK, one of the world’s top pharmaceutical companies, to license this exciting project. I am convinced that Apeiron’s know-how in this area, together with the extensive development and marketing capabilities of GSK, are the best way forward to bring an innovative therapy to patients worldwide.”

Manfred Reichl, Chairman of the Supervisory Board and business angel,

stated: “Remarkably, Apeiron achieved this major success without prior Venture Capital financing, but only with individual private investors. This proves that the Biotech cluster in Vienna has come a long way and is catching up to global standards in research quality, management capabilities and financing.”

About ARDS:

Acute Respiratory Distress Syndrome (ARDS) is an acute, severe injury to the lungs associated with a variety of conditions, such as sepsis, aspiration of acidic gastric contents, trauma, postoperative complications, acute pancreatitis, and pneumonias e.g. due to infections with human influenza viruses. According to recent analyses, it affects millions of individuals worldwide/year (up to one million in OECD countries alone). ARDS has a mortality rate of 30-50% and, up to date, no effective drugs exist to treat this life-threatening condition.

About Apeiron:

Apeiron Biologics AG is a privately financed biotech company in Vienna, Austria, founded by Josef Penninger, Director of the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA). As its main project Apeiron has developed recombinant human Angiotensin Converting Enzyme 2 (rhACE2; project name: APN01) as biotherapeutic up to Phase I clinical trials. Target indications for APN01 are diseases with an imbalance of the Renin Angiotensin System and insufficient natural ACE2 activity.

Special focus was devoted to explore the therapeutic potential of rhACE2 for the treatment of ARDS. In addition to its activities for APN01, Apeiron pursues two additional projects in preclinical development, also stemming from research activities of Josef Penninger.

Scientists Associate Modified Form of Protein with Parkinson, Alzheimer and Huntington diseases


Scientists Associate Modified Form of Protein with Three Neurodegenerative Diseases

GEN News Highlights

Prof. James Eberwine, from Department of Neuroscience, University of Pennsylvania

Researchers from the University of Pennsylvania School of Medicine have identified the same toxic form of a protein known as Elk-1 within the abnormal inclusions found post-mortem in the brains of patients with Parkinson, Alzheimer, and Huntington diseases. Their results suggest that it is involved during a key stage of disease pathogenesis common to neurodegenerative diseases.

Their study is published in PloS One in a paper titled “A Neurotoxic Phosphoform of Elk-1 Associates with Inclusions from Multiple Neurodegenerative Diseases.”

It is known that the transcription factor Elk-1 resides in both nuclear and extranuclear neuronal compartments, but when present in nerve cell dendrites it can trigger neuronal death. In the current research, the team used phototransfection to focally introduce and express small amounts of Elk-1 mRNA into various compartments of a single primary hippocampal neuron.

Following phototransfection and expression of Elk-1 mRNA within dendrites, the majority of neurons undergo cell death that could be seen as early as 30 minutes to several hours later.

To investigate the possible link between normal or abnormal Elk-1 and neurodegenerative diseases, the researchers next determined the importance of Elk-1 post-translational modifications on its ability to initiate regionalized cell death. The resulting data suggested that the ability of Elk-1 to initiate regionalized neuronal death depended on a specific phosphosite T417.

They then screened human cases of Parkinson, Alzheimer, and Huntington diseases to look for abnormal levels of the Elk-1 and/or the modified phospho-modified Elk-1 protein, pElk1 as well as to assess their association with inclusions characteristic of these diseases. The results confirmed that pELK-1 was uniquely associated with the Lewy bodies in Parkinson disease, with the classic plaque, tangle, and thread morphologies in the Alzheimer brain, and the ubiquitin-containing inclusions in Huntington disease brain tissue.

“The co-localization of T417+ELK-1 with mutliple neuronal inclusions suggests a common mechanism of pathogenesis and neuronal loss among distinct neurodegenerative diseases,” the authors state.

“The linkage between Elk-1 and neurodegeneration raises an interesting set of issues regarding its potential as a therapeutic target. Its association with several types of inclusions suggests its involvement during an important stage of disease pathogenesis shared across a spectrum of neurodegenerative disease.”GEN_logo

U.S. rights group argues against human gene patent


By Edith Honan

Patents on two human genes associated with breast and ovarian cancer should be declared invalid because they stifle the free flow of information and hamper research, lawyers told a New York judge on Tuesday.

A lawsuit brought by the American Civil Liberties Union and other groups last May posed a broad challenge to gene patenting and its outcome could have far reaching effects because one in five human genes are patented.

The specific case argued on Monday at Manhattan federal court concerned a patent on two genes held by Myriad Genetics (MYGN.O). Mutations on those genes are responsible for most cases of hereditary breast and ovarian cancers.

“(Myriad) uncovered a law of nature … and they deserve credit for having done so. But laws of nature are not patentable,” said Chris Hansen, an attorney with the ACLU.

But a lawyer for Myriad dismissed the litigation as a test case to “go after gene patents and the biotech industry as a whole” and said patents have a positive impact on human health because they promote innovation.

“This is not nature’s handiwork… this is the hard work of man,” said Brian Poissant, a lawyer for Myriad.

It could be months before the judge issues a ruling.

The lawsuit by the ACLU, the Association for Molecular Pathology, individual women and others was brought against the U.S. Patent and Trademark Office, Myriad Genetics and the University of Utah Research Foundation, which hold the patents on the BRCA1 and BRCA2 genes. (Editing by Daniel Trotta and Chris Wilson)

FDA to review Teva biosimilar of Amgen’s Neupogen


* FDA accepts filing of biosimilar to be called Neutroval

* Teva shares up 1.4 pct, Amgen shares off slightlyNeupogen

Generic drugmaker Teva Pharmaceutical Industries Ltd (TEVA.TA) said on Tuesday the U.S. Food and Drug Administration will review its application to sell a biotechnology medicine to boost white blood cells that is similar to Amgen Inc’s (AMGN.O) big-selling Neupogen.

Teva said the FDA accepted its Biologics License Application for the medicine for which it has proposed the trade name Neutroval.

The Teva drug, XM02, is already being sold under the name TevaGrastim in several European countries, where a pathway for approving generic versions of biotech drugs — so-called biosimilars — is already in place.

No such pathway for generic biotech medicines exists yet in the United States. The U.S. Congress has been weighing creation of a process for companies to seek approval of generic biotech medicines as part of stalled healthcare reform legislation.

In the absence of a U.S. route to generic biotech drugs, Teva said in December that its FDA application treats XM02 as a new biotech medicine.

The Teva drug, like Amgen’s Neupogen, is used to boost white blood cells in cancer patients undergoing some types of chemotherapy that can cause severe neutropenia, or low white blood cell count.

Amgen, which has not yet had to face any generic competition for its medicines in the United States, reported combined worldwide sales of $4.64 billion in 2009 for Neupogen, known chemically as filgrastim (G-CSF), and a related medicine Neulasta.

Teva shares were up 79 cents, or 1.4 percent, at $57.45 on Nasdaq, while Amgen shares were off 4 cents to $58.68 also on Nasdaq. (Reporting by Bill Berkrot; edited by Gunna Dickson)

Crafting Light-Sensing Cells from Human Skin


Photoreceptors created from induced pluripotent stem cells.

By Janelle Weaver

Photoreceptors from skin: A photoreceptor cell (green) derived from human skin cells incorporates itself into a mouse retina (red). Credit: Thomas Reh

Think twice the next time you wipe a few flecks of dandruff from your shoulder. You might be shedding cells that may someday restore human vision.

Thomas Reh and colleagues at the University of Washington, in Seattle, have generated light-sensing retinal cells, called photoreceptors, from adult human skin cells. They then transplanted the cells into a mouse retina, showing that the photoreceptors integrated normally into the surrounding tissue. This technological feat raises hopes for the development of treatments for retinal diseases, such as retinitis pigmentosa and macular degeneration, which cause visual impairment or blindness in millions of people in the U.S.

Researchers used induced pluripotent stem (iPS) cell technology, activating a handful of genes in skin cells in order to revert them to a flexible embryonic state. They then used previously developed methods to differentiate the cells into photoreceptors. While Reh’s team has done similar experiments using embryonic stem cells, iPS cells are a preferable source for cell replacement therapies because they can be derived from the patient. Skin cells are a ready source of cells that are tissue-matched to the recipient, bypassing problems associated with immune rejection of stem-cell transplants.

The cells also provide a new way to study retinal degeneration diseases and to identify drug targets. Retinitis pigmentosa, for example, is an inherited disorder in which the photoreceptors begin to die. Retinal cells derived from a patient with the disease harbor all the genetic mutations that contributed to the patient’s disease, so scientists can try to determine the molecular mechanisms that lead to cell death. They can then use the cells to screen for molecules that can slow or stop the damage.

“There are no good drugs to slow photoreceptor degeneration,” said Reh, a neurobiologist at the University of Washington. “One reason we don’t have more molecules we can test is that we don’t have good animal models for many human retinal diseases.”

Scientists will still need to overcome some serious hurdles before using the cells for transplantation therapies. The genetic flaws that led to the disease would need to be fixed before implanting the cells into the eye. And researchers need to figure out how to get large volumes of cells to integrate effectively into the retina. In the current experiments, published last month in the journal PLoS ONE, the number of cells that took root in the mouse eye was too low to restore visual sensitivity. “We need about 10,000 cells to integrate into the retina for them to restore function,” Reh said.

Future research will have to explore how well the transplanted photoreceptors connect with other cell types in the retina and function as an integrated circuit. “The work still ahead is huge,” said Robert Lanza, chief scientific officer at Advanced Cell Technology. “But this is a very important first step.”

Copyright Technology Review 2010.

Israel: New biomed index attracts more cautious investors


Investors have taken big risks, seeking big returns.

Gali Weinreb 25 Jan 10 15:13
Last week the Tel Aviv Stock Exchange (TASE) announced that it plans to launch an index of biomed companies. It is not yet clear when the index will be launched but the TASE has already indicated the criteria required for being part of the index.The weight of a single company in the index will be capped at 9.5% and the index will include all companies with a minimum market cap of NIS 50 million, and free float of at least 20% with a market cap now lower than NIS 25 million.According to the criteria, 24 of the 40 biomed companies traded on the TASE will qualify. Market analysts approve of the concept, and in particular approve the introduction of new instruments such as Exchange Traded Funds (ETFs) to track the index. The belief is that the launch of new ETFs will attract a new type of more conservative investor.Most of the biomed shares are currently held by three types of investors: those who feel that they understand the sector well enough to choose which biomed companies are most promising; those who like the potential of a specific share and stick by it; and investors who like risk and are prepared to gamble about certain developments. Biomed is very much a “boom or bust” sector, which infatuates the third type of investor.

The investors who will be drawn to the ETFs will be those who do not understand the sector well enough to choose a specific share, and anyway are not interested in buying a specific stock but rather believe in the sector, and that a group of biomed companies traded in Tel Aviv can triumph in the market.

But are there enough investors in have faith in the overall sector? We will only see after the ETFs are launched. During 2009 a list of biomed shares rose by even more than the Tel Aviv 25 index. However, those biomed shares had fallen more sharply than the Tel Aviv 25 in 2008, and in 2009 many speculators bought biomed shares to take advantage of the volatility of these shares. ETFs can reduce the volatility of this sector.

Despite expectations of new groups of investors entering the biomed market, analysts believe that in the short term, after the launching of the ETFs, the market will not be flooded with enough buyers to raise the prices of the shares in the ETFs. The biomed sector is already the focus of attention, and when the new money is invested in the ETFs, some current investors will take advantage of the situation to indulge in profit taking.

The TASE has placed the bar at a height that will enable a relatively large number of companies – slightly more than half the biomed companies traded on the TASE – to be a part of the new index. This spread will facilitate a spread of risk, while also allowing volatile shares to enter the index. Investors in biomed ETFs will be able to diversify the risks, while also investing in an index of companies in their initial and relatively risky phases. From the point of view of the biomed industry, the index has got to be a good idea.

Published by Globes [online], Israel business news – www.globes-online.com – on January 25, 2010

© Copyright of Globes Publisher Itonut (1983) Ltd. 2010

Keryx cancer drug improves survival in mid-stage trial


Says drug shows more than 60 pct improvement in survival

Keryx Biopharmaceuticals Inc (KERX.O) said a mid-stage trial showed its colon cancer drug improved overall survival in heavily pre-treated patients with advanced metastatic colon cancer, as compared with a dummy drug, sending its shares up 13 percent in premarket trade.Colon Cancer

The study enrolled a total of 38 patients, who were either given the drug KRX-0401, or perifosine, in combination with a chemotherapy drug capecitabine, or just capecitabine in combination with a dummy drug. Patients receiving KRX-0401 showed a greater than 60 percent improvement in overall survival and also demonstrated statistically significant advantage for time to progression, the company said in a statement.

However, the patients on the drug showed a higher incidence of adverse events like anemia and hand-foot syndrome as compared with those on the dummy drug.

“We are eager to finalize the design of a Phase 3 protocol in metastatic colorectal cancer within the next 3 months, in consultation with the FDA, and to commence the Phase 3 study as soon as practicable thereafter,” Chief Executive Ron Bentsur said in a statement. Perifosine is currently being tested in another late-stage trial for the treatment of relapsed/refractory multiple myeloma.

Shares of the company were up 13 percent to $3.11 in premarket trade. They closed at $2.74 Friday on Nasdaq.

QUINTILES ANNOUNCES NEW POSITIONING, NEW BRAND IDENTITY


Anticipating Biopharma Needs in a New Landscape

Research Triangle Park, NC, – Quintiles, the world’s leading biopharmaceutical services company, has launched a new positioning and brand identity, driven by the company’s growing ability to solve customers’ emerging clinical and commercial challenges.

Quintiles

The New Health

“The New Health is our description of the rapidly changing world of biopharma,” said Quintiles Chief Operating Officer John Ratliff. ”

We define the New Health in a number of ways, both as a journey and as a destination. The te

rm encapsulates the risks and opportunities biopharma faces in today’s changing economic and healthcare settings.”

Biopharma companies are under relentless pressure to increase speed and productivity, streamline development processes and create better value and greater accessibility for patients worldwide. The scale and pace of changes associated with the current and future state of the industry threaten to make the traditional biopharma business model irrelevant in the years to come.  [See a video of a Quintiles executive explaining what “The New Health” means to him.]

“Only Quintiles has the ability to provide integrated clinical, commercial, consulting and capital solutions across the globe,” said Ratliff. “Only Quintiles has the breadth and agility, talented people and unwavering commitment to patient stewardship necessary to help our customers navigate the risks and seize the opportunities in The New Health.”

“Our differentiation is to leverage this unique combination of service offerings,” Ratliff said. “We are now ready to ask customers to think about Quintiles differently. We do this by providing innovative perspectives and more productive practices, addressing customers’ need for change and building on Quintiles’ history for pioneering new approaches.”

A Single Brand
Quintiles’ new positioning includes the introduction of a unified brand, a fresh new visual system, an updated logo and new company tag line, all designed to communicate the company’s business approach and the transformative changes it is making within the biopharmaceutical industry.

“The Quintiles name now serves as the umbrella brand for Quintiles’ global services with offerings represented as Clinical, Commercial, Consulting and Capital,” explained Quintiles Chief Marketing Officer and Senior Vice President Millie Tan. “This is purposeful, as it clearly conveys our distinct areas of expertise while demonstrating the company’s breadth of capabilities.”  The new tag line, “Navigating the New Health,” communicates that Quintiles is an ally to help customers meet intellectual and executional demands in a rapidly changing marketplace.

Quintiles new brand identity is being launched behind a powerful advertising campaign that communicates a patient-centric vision of change. The first wave of repositioning will be launched in online advertising and will be followed by a sustained trade and business media print campaign across the United States, Europe and Japan.

About Quintiles
Quintiles is the only fully integrated biopharmaceutical services company offering clinical, commercial, consulting and capital solutions worldwide. The Quintiles network of 23,000 engaged professionals in more than 50 countries around the globe works with an unwavering commitment to patients, safety and ethics. Quintiles helps biopharmaceutical companies navigate risk and seize opportunities in an environment where change is constant.

New Products to Treat Neglected Diseases Are on the Rise


Joshua Cohen

Dr Joshua Cohen, senior research fellow at Tufts CSDD and author of the study.

New products to treat neglected diseases have received marketing approval from regulatory agencies at a steadily increasing rate in recent years as R&D funding for those diseases has increased, according to a recently completed study by the Tufts Center for the Study of Drug Development.

According to the study, the annual rate of new product approvals worldwide for neglected diseases increased from an average of 1.8 in 1975-99 to 2.6 in 2000-09.

Neglected diseases include malaria, kinetoplastids, diarrheal diseases, helminths (e.g. roundworm), bacterial pneumonia and meningitis, and typhoid and paratyphoid fever.

“During this past decade, a significant increase in R&D funding for neglected diseases has led to marketing approval for 26 drugs and vaccines,” said Joshua Cohen, senior research fellow at Tufts CSDD and author of the study.

He added, “While increased approvals are necessary to improve access, policymakers need to ensure that safe, effective, and easy-to-administer products are adopted by health care systems and providers on a consistent basis, that they are affordable, and that they reach the people who need them.”

The Tufts CSDD analysis examined the results of a widely circulated 2002 study, which reported that only 16 of 1393 new chemical entities marketed between 1975 and 1999 targeted tropical diseases and tuberculosis. Tufts CSDD found that the more accurate count was 33. However, the earlier study prompted governments, nonprofit foundations, and private-public partnerships to increase funding for neglected diseases, from less than $100 million annually a decade ago to more than $2.5 billion annually today.

The new analysis, reported in the November/December Tufts CSDD Impact Report, released today, also found that:

*  Drugs to treat HIV/AIDS and malaria accounted for 81% of approvals during 2000-09.

*  Vaccines have displaced drugs as the main products being developed for neglected diseases, accounting for 76% of all products in development to treat neglected diseases.

*  Public-private partnerships accounted for 46% of all new product development to treat neglected diseased during 2000-09, up from 15% in the 1975-99 period.

About the Tufts Center for the Study of Drug Development

The Tufts Center for the Study of Drug Development (http://csdd.tufts.edu) at Tufts University provides strategic information to help drug developers, regulators, and policy makers improve the quality and efficiency of pharmaceutical development, review, and utilization. Tufts CSDD, based in Boston, conducts a wide range of in-depth analyses on pharmaceutical issues and hosts symposia, workshops, and public forums, and publishes the Tufts CSDD Impact Report, a bi-monthly newsletter providing analysis and insight into critical drug development issues.

Ardea Biosciences switches its research from HIV to gout


Thankfully, Barry Quart’s HIV drug appeared to be working. In recent Phase 1 testing, the compound, which blocks the activity of an enzyme HIV needs to continue its replication cycle, appeared to be well tolerated and had no notable side effects.

But while skimming the data in preparation for a board meeting, Quart noticed something. The patients taking the drug exhibited a dramatic decrease in levels of uric acid, a breakdown product of purine. Elevated uric acid levels, a condition known as hyperuricemia, are a hallmark of gout, a disease that causes kidney damage and painful attacks of arthritis when uric acid in the bloodstream crystallizes and deposits in the kidneys and joints.

As Quart recalls, after he shared this with the board, one member piped up: “Are you crazy? There’s a company developing a biologic that lowers uric acid levels and has a market capital worth $1 billion.” Instantly, Quart, CEO and director of Ardea Biosciences in San Diego, began thinking about changing the focus of his company.

How one company suddenly switched its focus from HIV to gout.

Quart had started the small biotech in the 1990s to develop HIV drugs after pioneering some of the very first antiretrovirals. “In the early days, [HIV research] was an exciting place to be,” says Quart. “I was generating drugs for patients with a huge need. These days there’s less medical need for newer HIV agents.” The market for new gout drugs, on the other hand, is wide open.

Despite afflicting an estimated two to six million Americans, the standard approach for treating gout over the last 40 years has been a drug called allopurinol, which inhibits an enzyme that produces uric acid. However, “this drug has a lot of side effects and about 60 percent of patients don’t get a good response,” says Quart. A recent, more potent version of allopurinol, called uloric, can cause debilitating side effects, and 25 percent of people on the drug still do not respond to treatment. “There is still a huge unmet medical need in gout care,” says Quart. “The opportunity to develop this interesting gout drug was too exciting to pass up.” Historically, this kind of switch is not unprecedented—Viagra, a drug for erectile dysfunction, was initially meant as a heart medication.

First, Quart had to figure out how a medicine for HIV could also target gout. He set up several assays showing that when the body metabolized the HIV drug, the liver clipped it in half, producing one molecule that’s active against HIV and another that exhibited no activity against HIV but did lower uric acid. He found that the second metabolite inhibits a protein in the kidney which is responsible for regulating uric acid levels.

Quart realized he could isolate and develop the second metabolite as a gout drug. Quart also pursued the HIV drug through Phase 2 trials, but dividing the company’s resources between these two drugs became too expensive. After more than a decade of HIV work, Quart decided to shift his company’s focus and resources primarily to gout. (The company, however, does continue to work on several other therapeutic spaces, including HIV and cancer drugs.)

At the American College of Rheumatology meeting in October, Ardea Biosciences announced results from a Phase 2 trial, in which gout patients who took the drug showed increased urinary excretion of uric acid and demonstrated no serious side effects. Quart is proposing a two-pronged approach—administering his drug along with allopurinol or another drug that manages inflammation.

“Based on what was presented at the meeting recently, I don’t think you could say this drug is going to be the next big thing, but I think it will complement what’s available,” says Tuhina Neogi, a rheumatologist at Boston University who is a lead investigator in an online gout study looking at risk factors for repeated attacks. “Questions still remain about whether this drug will be any better than what we have already or if it will be safe to use in combination with other drugs. It’s just too early to tell.”

Quart says he hopes to have the Phase 3 trial completed by next summer and possibly a drug approved by 2012 or 2013. “This was indeed a serendipitous event,” Quart says

FDA Approves Ampyra to Improve Walking in Adults with Multiple Sclerosis


SILVER SPRING, Md. — The U.S. Food and Drug Administration today approved Ampyra (dalfampridine) extended release tablets to improve walking in patients with multiple sclerosis (MS). In clinical trials, patients treated with Ampyra had faster walking speeds than those treated with an inactive pill (placebo). This is the first drug approved for this use.

MS is a chronic, often disabling, disease that affects the central nervous system-the brain, spinal cord, and optic nerves. There are about 400,000 people in the United States and 2.5 million people world-wide with MS.

The progress, severity, and specific symptoms of MS are unpredictable and vary from one person to another. Symptoms can be mild, such as numbness in the limbs, or severe, such as paralysis or loss of vision. About half of all people with MS experience cognitive impairments like difficulties in concentration, attention, memory, and judgment, although these symptoms are usually mild and are frequently overlooked. Depression also is common among MS patients.

“Trouble with walking is one of the most debilitating problems people with MS face,” said Russell Katz, M.D., director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research.

Ampyra, when given at doses greater than that recommended (10 milligrams twice a day), can cause seizures. The most common adverse reactions reported by patients taking Ampyra in clinical trials include urinary tract infection, insomnia, dizziness, headache, nausea, weakness, back pain, balance disorder, swelling in the nose or throat, constipation, diarrhea, indigestion, throat pain, and burning, tingling or itching of skin.

Ampyra should not be used in patients with moderate to severe kidney disease. In these patients, blood levels with the drug approach those associated with the occurrence of seizures.

Ampyra will be manufactured under licenses from Elan of Dublin, Ireland, and distributed by Acorda Therapeutics Inc. of Hawthorne, N.Y.

The Latest Front In the War on Arthritis


By SHIRLEY S. WANG

Scientists looking for ways to repair damaged cartilage—a leading cause of osteoarthritis—are employing horses to test a new method of tissue regeneration that uses concentrated stem cells.

Constance Chu, an associate professor and director of the Cartilage Restoration Center at the University of Pittsburgh, and Lisa Fortier, an associate professor of large-animal surgery at Cornell University’s veterinary school, are testing the new procedure on former racehorses and rodeo horses to determine if it is more effective than a commonly used cartilage repair treatment in the U.S. called “microfracture.”

They are also looking for biological markers that could help doctors diagnose earlier patients with cartilage damage and indicate which ones may be most responsive to tissue regeneration.

Cartilage, the strong but flexible material that coats bones at the hip, knee and other joints, can be weakened with overuse and age, and can be permanently damaged when someone twists a knee on the soccer field or dislocates a shoulder. Cartilage that has been torn or injured doesn’t naturally grow back, and treatment options remain limited.

Over the long term, cartilage injury increases the risk of osteoarthritis, a painful chronic condition and the most common form of arthritis. It affects almost 27 million Americans, according to the Arthritis Foundation.

To decrease pain, improve functioning and slow the disease’s progression, osteoarthritis is usually treated through a combination of medication, physical therapy to strengthen muscles and improve flexibility, a weight-loss program, and splints and braces. In severe cases, patients may undergo arthroscopic surgery to repair cartilage tears and remove loose tissue, or joint-replacement surgery. Some alternatives to traditional therapy include the use of the supplement glucosamine, which research shows may promote cartilage repair and formation, and vitamins like C and E that may help slow cartilage erosion and reduce pain.

Yet there isn’t any good way of detecting cartilage breakdown until the cartilage is broken or lost or osteoarthritis develops. And though cartilage-repair surgery has improved over the years, the repaired scar tissue isn’t as strong as real cartilage and isn’t able to bear the same weight. Patients who get surgery at 20 years old—as athletes who get injured often have to do—may develop osteoarthritis in their 30s and 40s and need additional surgery.

For about two decades, Dr. Chu and other researchers in the field have been trying to improve treatment by regenerating cartilage tissue. While many scientists have been successful at creating new tissue in the lab, they haven’t been able to grow cartilage in humans. The main challenge is that the structure of cartilage, which is critical to its supporting weight, is hard to mimic, says Fei Wang, director of the Musculoskeletal Tissue Engineering and Regenerative Medicine Program at the National Institute of Arthritis and Musculoskeletal and Skin Diseases in Bethesda, Md., which funds many researchers working on cartilage regeneration.

“It’s easy to generate a piece of tissue, but it’s not so easy to generate a tissue that works,” says Dr. Wang.

Over the last 10 years, Dr. Chu has also been studying how to identify cartilage injury at a reversible stage—that is, before the surface breaks down—and how to treat damaged cartilage and osteoarthritis more effectively.

Consisting mostly of water, cartilage is made up of a tough scaffold structure that encloses the water, much like a water bed. If the structure of the cartilage is ruptured, its integrity is destroyed and the fluid escapes. Thus any regenerated tissue needs to include a structure capable of bearing weight.

Not only is cartilage repair difficult, but it is hard to diagnose as well. Patients don’t feel pain—cartilage doesn’t contain any nerve endings—and there aren’t good tools for detecting injury to it until it becomes permanently damaged. People often don’t know they have a problem until they develop a more-serious disease that causes pain after the cartilage has further eroded.

Yet damage is likely to occur immediately after injury. Last month, Dr. Chu published a study in the Journal of Sports Medicine showing that even when cartilage appears visually healthy after a trauma, many of the cells underneath the impact site quickly die. If there was a way of immediately detecting and treating the cartilage damage, these people could be spared years of arthritic pain and disability, she says.

Dr. Chu is studying new imaging techniques for early detection of cartilage damage. For example, optical coherence tomography, which provides a three-dimensional image by scattering light through tissue, potentially has the ability to give detailed images of cartilage but without damaging the tissue, says Dr. Chu. She published work on this imaging technique in the Journal of Orthopedic Research in October.

Dr. Chu is also researching better ways for surgeons to treat cartilage damage in humans. She and her collaborators at Cornell University, Colorado State University and University of California, San Diego, recently began a study—funded by $1.7 million federal grant—looking at a new way of promoting cartilage growth by studying horses.

With microfracture, which has been growing in popularity as a way to treat patients soon after acute injury, surgeons puncture tiny holes into the bone beneath the damaged cartilage, prompting blood and bone marrow to fill the holes. The theory is that some of the bone marrow contains stem cells—which are cells that can grow into different types of cells—and other growth-promoting cells in the blood, a process that generates cartilage-like scar tissue. But this tissue isn’t as strong and doesn’t work as well as real cartilage, and the long-term benefits of the surgery aren’t well researched, according to Ranjan Gupta, professor and chairman of orthopedic surgery at the University of California, Irvine.

Currently, “all of our best efforts create inferior tissue to what we are born with,” says Dr. Chu. Cartilage transplant appears to be effective in filling the damaged cartilage, but isn’t widely available because it is difficult to find healthy cartilage for use in the transplant. “Just because we can’t get [the tissue] perfect unless it’s through transplant doesn’t mean we shouldn’t keep trying to improve the repair,” says Dr. Chu.

In the current study, she and her colleagues hypothesize that the more stem cells that are used to repair cartilage at the site of the damage, the better the regeneration of the tissue should be. They first create a dime-sized cartilage injury in the horse’s stifle joints, which resemble the human knee, and then test two different ways of concentrating the stem cells after taking them from the horse’s own bone marrow to see if either is better than microfracture and how they compare with each other.

One experimental method involves taking bone marrow and immediately spinning the sample in a centrifuge to separate out the part where the stem cells are mostly likely to be, while removing as much of the extra fluid and materials found in bone marrow as possible. The benefit of this technique is that it can be done during the surgery and used in the treatment, says Dr. Chu. The second method entails taking the stem cells from the bone marrow and growing them in a laboratory, which should yield the best crop of stem cells but would take a lot longer and involve additional procedures, she says.

Each horse in the study will be examined at 10 days and three months post-surgery for signs of cartilage repair. So far, 11 out of a total 12 horses have had the surgery. By three months, the injury should be filled with new tissue, says Dr. Chu.

If the use of blood concentrate in the horses appears to repair cartilage better than microfracture, Dr. Chu plans to undertake a similar clinical study on humans, which she estimates would begin in about two years.

Stelara outperforms Enbrel for advanced psoriasis, study finds


A recently approved drug, Stelara, is more effective than a more established drug, Enbrel, in treating moderate to severe psoriasis, according to a new study.

The findings, reported this week in the New England Journal of Medicine, may help patients whose extensive psoriasis is not well-controlled to find an alternative treatment.

“I think it’s pretty clear that Stelara is a dramatically effective drug, one of the most effective drugs we’ve ever had for psoriasis,” Mark Lebwohl, MD, chairman of the dermatology department at Mount Sinai School of Medicine, tells WebMD. Lebwohl’s department was one of 67 sites worldwide to participate in the study.

Both Stelara and Enbrel are biologics — treatments made up of genetically engineered proteins — and used to treat patients who have moderate to severe psoriasis that has not responded to traditional systemic therapies such as methotrexate.

But the two drugs have completely different mechanisms of action. While Enbrel blocks tumor necrosis factor-alpha (TNF-alpha), Stelara targets two inflammatory chemicals, interleukin 12 and interleukin 23, which are involved in the pathogenesis of psoriasis.

Study researcher Christopher Griffiths, MD, a professor of dermatology at England’s University of Manchester Medical School, says if patients taking Enbrel have well-controlled psoriasis, they need not switch to Stelara.

The study’s conclusion “just gives those individuals the reassurance that if for some reason the Enbrel stops working, or wasn’t working as effectively as it was at the beginning, that there’s a proven, logical alternative therapy that they could switch to.”

In the study, 903 patients with moderate-to-severe plaque psoriasis got either Stelara (high or low dose) or high-dose Enbrel.

Comparing Enbrel and Stelara

At week 12 of the study, 65% of patients in the lower-dose Stelara group and almost 71% of those in the higher-dose Stelara group had, at most, minimal signs of their psoriasis, according to their doctors, compared to 49% of patients treated with Enbrel.

“We’ve never had a drug that with so few injections worked so well,” Lebwohl says. Patients in the Sterlara group got one injection when they started the study and another one four weeks later; patients receiving Enbrel received two injections every week for 12 weeks.

Lebwohl says he’s not surprised by the study’s outcome. “We’ve been hearing about [Stelara] for years.” It has already been on the market for one year in Europe and two years in Canada.

The study was sponsored by Centocor, the pharmaceutical company that makes Stelara. Lebwohl has served as an investigator for both Centocor and Amgen, the company that manufactures Enbrel.

Lebwohl’s advice to individuals with psoriasis is to weigh their options. Many patients do well on Enbrel, and it has a long safety track record. Stelara, on the other hand, is “dramatically more effective” but it has not been around long enough to fully gauge how safe it is, he notes.

Data from the 12-week study found that within this short frame, the safety of the two drugs was generally similar. However, Lebwohl cautions that three months is too short a time to determine if Stelara will eventually increase the risk for infections or cancer. Biologic agents affect the body’s immune system, which explains this potential risk.

Sonia Fiorenza, Amgen’s director of corporate communications, echoes these safety concerns in an email. Dermatologists’ No. 1 concern in treating psoriasis is long-term safety. While Enbrel has an established safety profile with more than 17 years of collective clinical experience, this study does not provide comparative efficacy and safety data beyond three months, she writes.

Psoriasis affects at least 2% of the world’s population. For the most part it is a young person’s disease, with three-quarters of cases appearing before the age of 40. It is not contagious and there is no cure.

People with moderate to severe psoriasis face significant psychosocial difficulties including depression and isolation. Often they will avoid public places like swimming pools or gyms because even though psoriasis is not contagious, the public perceives it to be so, Griffiths says.

“The advent of the biologic therapies has been life transforming for a lot of patients,” he notes.

Genzyme Investor Suggests Sale of Some Businesses and concentrate on genetic disease


By Elizabeth Lopatto

(Bloomberg) — Genzyme Corp., the world’s largest maker of genetic disease drugs, should sell businesses that don’t focus in that area, said Ralph Whitworth, the head of Relational Investors LLC.

Genzyme’s renal business, which includes Renagel and Renvela, is a poor investment, Whitworth said in an interview. Those two drugs generated $677 million in 2008.

Relational Investors, Genzyme’s fifth-largest shareholder, wants the Cambridge, Massachusetts-based company to focus on its genetic disease treatments, which had sales of $2.23 billion in 2008, accounting for half of the drugmaker’s revenue. Over the last 25 years, Genzyme had a $1.3 billion loss in pre-tax earnings if genetic disease drugs such as Cerezyme were excluded, wrote Yaron Werber, an analyst for Citigroup, in a Jan. 12 note to investors.

“We want to bring discipline to the financial side,” said Whitworth, a founder and principal of Relational Investors, in an interview yesterday. “The discipline increases the likelihood that money’s well-spent.”

Genzyme shares rose 52 cents to $53.50 at 4:14 p.m. New York time in Nasdaq Stock Market composite trading. The company fell 17 percent in the last 12 months.

Genetic-Disease Drugs

Genzyme’s genetic-disease drugs had a return of invested capital of 25.8 percent in 2008, Werber said in his research note. That is a measure of how well a company uses its money from debt and equity markets. Excluding those drugs, Genzyme returned 8.8 percent in 2008.

In 2009, contamination forced its Allston Landing plant to close, creating shortages of its best-selling Cerezyme. The company’s 2009 revenue shrank 2 percent to $4.5 billion because of the shortages, Chief Executive Officer Henri Termeer announced at a J.P. Morgan healthcare conference yesterday.

Though San Diego-based Relational is “disgruntled” by the stock performance, the firm has not called for a change in management, Whitworth said. On Jan. 7, he deferred his request for board representation and agreed to support the company’s slate of directors in 2010. If he requests representation by November, he’ll be appointed to the board, according to the agreement.

Carl Icahn

Billionaire investor Carl Icahn is also an investor in Genzyme, having acquired a $72 million stake in the company during the third quarter. Icahn held 1.45 million Genzyme shares as of Sept. 30 after holding none three months earlier.

Termeer said yesterday that he hadn’t spoken to Icahn. Whitworth said in the interview that he didn’t speak to Icahn about Genzyme.

Genzyme said in June it would ration two drugs, Cerezyme and Fabrazyme, after the company closed its Allston Landing plant in Boston to decontaminate after detecting a virus called Vesivirus 2117. Most of Genzyme’s medicines treat hereditary disorders caused by lack of enzymes needed for critical bodily functions. the same period a year earlier.

Gaucher disease treatment Cerezyme is Genzyme’s biggest product. People with Gaucher lack an enzyme needed to break down a type of fat that accumulates in organs and bones, causing liver and spleen enlargement, anemia, bruising and bone pain. Gaucher affects about 10,000 people worldwide.

Fabrazyme treats Fabry disease, an inherited illness in which lipids build up to harmful levels in the eyes, kidneys, nervous system and cardiovascular system. Fabry disease affects 5,000 to 10,000 people.

Last Updated: January 13, 2010 16:21 EST

MOLECULAR BIOMETRICS CLOSES $12.5 MILLION SERIES B EQUITY FUNDING


Molecular Biometrics®, Inc., a metabolomics company developing novel clinical diagnostic tools for applications in personalized medicine, today announced it has completed a $12.5 million Series B financing. New investor Atlas Venture (Waltham, MA) led the round with participation from existing investors.

The financing will allow the company to accelerate the global launch of the company’s lead product, ViaMetrics-E™, a rapid, non-invasive procedure that is designed to enhance in vitro fertilization (IVF) outcomes; implement manufacturing and product enhancements; and complete its ongoing FDA clinical study. ViaMetrics-E aids in the identification of viable embryos having the greatest reproductive potential, thus improving pregnancy rates in IVF, and ultimately reducing the number of embryos transferred along with the complications and healthcare costs that accompany multiple births.

“This is a very exciting time for Molecular Biometrics,” said James T. Posillico, PhD, President and Chief Executive Officer, Molecular Biometrics. “We are expanding our commercial operations to support the international launch of ViaMetrics-E, while completing the necessary regulatory requirements to market the product in the United States. We believe that ViaMetrics-E will fill a large and growing unmet need in the IVF market. We are very pleased to be supported by such a strong group of investors, and we welcome their ongoing role in developing our company.”

“Reducing the risk of multiple births while, at the same time, improving IVF pregnancy rates has long been a major challenge in infertility treatment. Since ViaMetrics-E can accurately identify embryos with the greatest reproductive potential, fewer embryos can be implanted while maintaining or even improving pregnancy rates. The advent of ViaMetrics-E represents a significant advancement in the IVF field.” said Peter Barrett, a Partner in Atlas Venture’s Life Sciences group, who will be joining the company’s Board of Directors. “This new procedure can have an immediate and important impact on infertility treatment, and has already been well received by reproductive specialists worldwide.”

Metabolomics at Molecular Biometrics Metabolomics is a complex scientific process that identifies and measures individual signals from many small molecular compounds produced during cellular metabolism. The company’s novel technology platform creates a ‘metabolomic profile’ or ‘fingerprint’ of an embryo’s potential viability, prior to possible embryo transfer in an IVF cycle. Metabolomic profiling provides a simultaneous evaluation of large numbers of biomarkers that reflect embryo development in culture media.

Molecular Biometrics developed a proprietary near infrared (NIR) biospectroscopy platform for its metabolomic applications. This technology rapidly measures the vibrational energy ‘signatures’ produced by small molecule functional groups, creating a unique profile of molecules that are descriptive of cellular function and viability. The signatures are further analyzed by proprietary bioinformatics, which evaluates the biological and chemical data produced by NIR biospectroscopy, using sophisticated computer and statistical techniques to distinguish between the often subtle differences that separate normal physiology from the onset or progression of disease, or an individual’s response to therapeutic intervention.
About Molecular Biometrics® Molecular Biometrics, Inc. is applying novel metabolomic technologies to develop accurate, non-invasive clinical tools for use in personalized medicine to evaluate normal biologic function in health and in disease, and for drug discovery and development. The company’s proprietary technology is being applied in reproductive health, IVF and neurodegenerative disease (e.g., Parkinson’s disease). Molecular Biometrics is headquartered in Norwood, MA, with research and development facilities in New Haven, CT, and Montreal, Quebec.

‘Longevity’ Gene May Cut Dementia Risk


Richard B. Lipton

Richard B. Lipton

(BRONX, NY) – Scientists at Albert Einstein College of Medicine of Yeshiva University have found that a “longevity gene” helps to slow age-related decline in brain function in older adults. Drugs that mimic the gene’s effect are now under development, the researchers note, and could help protect against Alzheimer’s disease.

The paper describing the Einstein study is published in the January 13 edition of the Journal of the American Medical Association.

“Most work on the genetics of Alzheimer’s disease has focused on factors that increase the danger,” said Richard B. Lipton, M.D., the Lotti and Bernard Benson Faculty Scholar in Alzheimer’s Disease and professor and vice chair in the Saul R. Korey Department of Neurology at Einstein and senior author of the paper. As an example, he cites APOE ε4, a gene variant involved in cholesterol metabolism that is known to increase the risk of Alzheimer’s among those who carry it.

“We reversed this approach,” says Dr. Lipton, “and instead focused on a genetic factor that protects against age-related illnesses, including both memory decline and Alzheimer’s disease.”

In a 2003 study, Dr. Lipton and his colleagues identified the cholesteryl ester transfer protein (CETP) gene variant as a “longevity gene” in a population of Ashkenazi Jews. The favorable CETP gene variant increases blood levels of high-density lipoprotein (HDL) – the so-called good cholesterol – and also results in larger-than-average HDL and low-density lipoprotein (LDL) particles.

“Most work on the genetics of Alzheimer’s disease has focused on factors that increase the danger. We reversed this approach and focused on a genetic factor that protects against age-related illnesses.”
— Richard B. Lipton, M.D.

The researchers of the current study hypothesized that the CETP longevity gene might also be associated with less cognitive decline as people grow older. To find out, they examined data from 523 participants from the Einstein Aging Study, an ongoing federally funded project that has followed a racially and ethnically diverse population of elderly Bronx residents for 25 years.

At the beginning of the study, the 523 participants – all of them 70 or over – were cognitively healthy, and their blood samples were analyzed to determine which CETP gene variant they carried. They were then followed for an average of four years and tested annually to assess their rates of cognitive decline, the incidence of Alzheimer’s disease and other changes.

Amy E. Sanders

Amy E. Sanders

“We found that people with two copies of the longevity variant of CETP had slower memory decline and a lower risk for developing dementia and Alzheimer’s disease,”says Amy E. Sanders, M.D., assistant professor in the Saul R. Korey Department of Neurology at Einstein and lead author of the paper. “More specifically, those participants who carried two copies of the favorable CETP variant had a 70 percent reduction in their risk for developing Alzheimer’s disease compared with participants who carried no copies of this gene variant.”

Amy E. Sanders, M.D.The favorable gene variant alters CETP so that the protein functions less well than usual. Dr. Lipton notes that drugs are now being developed that duplicate this effect on the CETP protein. “These agents should be tested for their ability to promote successful aging and prevent Alzheimer’s disease,” he recommends.

Other co-authors of the paper, “Association of a Functional Polymorphism in the Cholesteryl Ester Transfer Protein (CETP) Gene with Memory Decline and Incidence of Dementia,” are Cuiling Wang, Ph.D., Mindy Katz, M.P.H., Carol A. Derby, Ph.D., and Nir Barzilai, M.D., from Einstein, and Laurie Ozelius, Ph.D., from Mt. Sinai School of Medicine.

The research was funded by the National Institute on Aging, one of the 27 institutes and centers of the National Institutes of Health.

Anika buys Fidia biopolymer’s unit for $34 mln


* Expects deal to add to earnings in second year

* To pay $17.1 mln cash, 2 mln shares

* Says to develop direct U.S. sales capability

* Sees FDA approval for osteoarthritis drug in H2 2010

* Shares up 1 pct

Dec 31 (Reuters) – Anika Therapeutics Inc <ANIK.O> said it acquired a unit of privately held Italian company Fidia Farmaceutici Spa in a cash-and-stock deal worth about $34 million.

Anika said it will pay $17.1 million in cash and offer about 2 million shares for Fidia Advanced Biopolymers (FAB).

The acquisition is expected to add to Anika’s earnings in the second year of combined operations, it said in a statement.

Anika also said that it will develop its own direct U.S. sales capability to capture significantly higher margins from the domestic sales of its single-injection osteoarthritis treatment, Monovisc.

“We are planning to leverage FAB’s strong distributor partners in Europe and Asia to enhance sales of Monovisc and Anika’s other products in new and existing international markets,” Anika Chief Executive Charles Sherwood said.

The company expects to receive the U.S. Food and Drug Administration’s approval for Monovisc in the second half of 2010.

Shares of Anika were trading up 1 percent at $8.60 in early morning trade Thursday on Nasdaq.

For the alerts, double click [ID:nWNBB4761] . (Reporting by Anand Basu in Bangalore; Editing by Unnikrishnan Nair)

Revance Therapeutics raises $25 million


Revance Therapeutics Inc. raised $25.62 million in venture funding, according to a filing with the Securities and Exchange Commission. Revance

The Newark business, started a decade ago, seeks drugs useful in skin treatments and so-called “aesthetic medicine.” It’s been studying a type of botulinum toxin in a gel “for the treatment of crow’s feet wrinkles.” Executives at Revance — its CEO is Daniel Browne — hope that this treatment, RT001, will be less painful than injected Botox treatments now on the market and will appeal to more people.

Over the summer, Revance licensed another botulinum toxin product to Medicis Pharmaceutical Corp. (NYSE: MRX) of Scottsdale, Ariz., getting $10 million up front and possible milestone payments in 2010 or later of up to $94 million. Medicis, which sells the dermal filler product Restylane, is an investor in Revance, too.

In this latest venture deal, Revance issued $5.7 million worth of special series D stock in exchange for principal and interest it owed on convertible notes.

In the past, Revance has raised venture capital from Singapore’s Bio*One Capital, Medicis, Essex Woodlands Healthcare Ventures, Vivo Ventures, Technology Partners, San Diego’s Shepherd Ventures and Palo Alto Investors.

Robert Byrnes, former CEO of wrinkle-treatment business Thermage Inc., sits on Revance’s board of directors.

CEO Browne started Revance with Jacob Waugh, M.D., who is chief scientific officer.

According to its web site, Revance is hiring in a variety of laboratory and maintenance type jobs.

Bust proves a boon for savvy biotech scavengers


Bay State’s unusually rich trove of used gear can make start-ups’ lives less expensive

By Carolyn Y. Johnson, Globe Staff  |  January 4, 2010

Cannibalism is rife with in the biotech industry!’ BARRY CANTON, cofounder of Ginkgo Bioworks

In a laboratory at Marine Industrial Park in Boston, a wall of stickers reads like an impromptu scorecard of the incessant churn of biotechnology companies.

Peeled from equipment now in use at the start-up Ginkgo Bioworks, the 10 labels bear the names of companies that no longer exist, changed names, were swallowed by bigger companies, or shifted their focus.

Now, their discarded equipment – the incubators, robotic liquid handlers, and centrifuges that used to be working on the next big thing – is being repurposed for the next, next big thing.

It turns out the home of one of the world’s biggest biotechnology hubs is also one of the greatest stores of high-tech hand-me-downs. It’s well known that the region’s universities and brainpower, and the flow of millions of dollars of investments, foster the vibrant life sciences community. But so do its failures.

“Cannibalism is rife within the biotech industry!’’ Barry Canton, a cofounder of Ginkgo Bioworks, wrote in an e-mail. His company has acquired an estimated $600,000 worth of recycled equipment – for about a 90 percent discount.

The lab benches are from Codon Devices, a prominent start-up that raised at least $31 million before closing last year. A lab refrigerator came from Epitome Biosystems, a venture-backed start-up in Waltham that shut its doors after selling its technology to another company.

Other castoffs came from online auctioneers who sell off companies’ assets, universities getting rid of old equipment, and even eBay.

“It’s a very common model,’’ said Nate Tedford, an instructor at MIT who once worked at Epitome, where he watched other start-ups in his building close or move on. “It was just incredible – you’d go pay your respects to the people, say, ‘Hey, how are you doing; what are you doing next?’ ’’ he recalled. Then, practically in the next breath, scientists would be laying claim to the soon-to-be leftovers. “It was like a total yard sale.’’

Cambridge Scientific, an equipment reseller, has outlasted many of its clients over the past 13 years. Unlike biotechnology companies, which can take years to turn a profit – if they ever do – the resale business has been steady, with about $3.9 million in sales expected this year, said operations manager Richard Epstein.

When the economy is sizzling, new, expanding companies come calling. But the allure of marked-down used equipment may be even greater in a down economy, and supply goes up as companies downsize or fail, he said.

“We sell to start-ups constantly – they love us because they can basically outfit two labs for the price of one. . . . But nowadays we sell to a lot of local hospitals, we sell to big companies,’’ Epstein said. “Any lab manager trying to stretch their dollars would look to us as an alternative.’’

On a recent day, two customers from India browsed the warehouse, looking for equipment for a vaccine manufacturing facility. There is a microscope and balance room, another room for high-end devices, and aisle upon aisle of everyday lab equipment – “things that get hot, things that get cold, and things that spin,’’ said the president, Barbara Pearlman.

Equipment sells for around half price. Microscopes range from $500 to $20,000, depending on the model, and a gleaming, high-end device used to analyze large molecules would sell for about $130,000.

There are no price stickers on the equipment, in part, said Epstein, because “we are open to offers – not to sound too much like a used car dealer.’’

Companies typically acquire used equipment through a number of channels, said Michael Raab, a cofounder of Agrivida, a Medford company that is developing crop varieties better suited for biofuel production. Overall, Raab said, his 35-person company has probably paid about 50 percent of the list price for its equipment by making smart choices about what to buy new, and what to buy from resellers and auctions – as well as by knowing when a company is about to go belly-up.

“Usually, we keep an eye out for companies where we know people who are working and they’re saying, ‘Geez, it’s not looking good,’ ’’ Raab said. “We’re just opportunistic about it.’’

For David Preminger, a mechanical engineer who has become a dealer for biotechnology and semiconductor equipment, working with failed biotechs is less heartbreaking than working with semiconductor companies.

“You don’t hear people say, ‘My life is wrecked,’ ’’ Preminger said, noting there are so many new ventures and companies they can work for. “It’s easier emotionally, because it’s not fun to be a grave hunter.’’

He said his business has continued growing, despite the economic downturn, and that he is seeing signs of life, as new companies are beginning to call, anticipating getting funding in the first quarter of this year.

At Ginkgo Bioworks, Canton jokingly pointed out his company’s equipment tag is plain white, with a small barcode, and the company name spelled out in plain lettering. It is less flashy than the colorful metallic stickers the scientists have pried off some of their used equipment.

“So if anything bad happens,’’ Canton said, “it won’t look like we have spent a lot on fancy tags.’’

Carolyn Y. Johnson can be reached at cjohnson@globe.com.

A "shocking" new therapy tackles impotence


An Israeli researcher finds that the device that blasts kidney stones with shockwaves appears to have a restorative effect on the blood vessels of the penis.

By Karin Kloosterman

Treating impotence: Dr. Yoram Vardi, head of the Neuro-Urology Department of Ramban Medical Center

 

For the 35 million men in America alone who suffer from impotence, the issue of erectile dysfunction is no joke. Wonder drugs like Viagra and Cialis have rejuvenated many a couple’s sex life, but not without the associated risks of heart attack and adversely affected vision.

New research from Israel presented to the European Society of Sexual Medicine in Lyon, France in November suggests that a “shocking” new therapy might work to reinvigorate the male sexual organ in a very safe and effective manner. So far, the benefits of the treatment appear to be long lasting.

Dr. Yoram Vardi, head of the Neuro-Urology Department at the Ramban Medical center in Haifa, Israel, has found that the same device that uses shockwaves to blast kidney stones appears to have a restorative effect on the blood vessels of the penis.

In an initial study of 20 middle-aged men with erectile dysfunction – an inability to maintain an erection – for more than three years, researchers conducted a series of treatments that comprised three weeks of shockwave therapy administered in two 20-minute sessions each week.

No pain, all gain

The patients were allowed to rest for three weeks and then an additional course of low-dose shockwave treatments, with about 100 bars of pressure per shockwave, was administered over another three-week period, using a device that resembles a computer mouse.

Vardi found mostly consistent results in all 15 of the 20 men who benefited from the therapy. All the men noted a return of erectile functioning around the seven-week mark, and a six-month follow-up found that for 13 of the men, the effects were long lasting, while two will require additional treatments.

“There was no pain or additional side effects within six months,” Vardi tells ISRAEL21c. “There was an improvement [in erectile function]. A huge improvement.”

How does he explain it? “We feel the effect is something biological,” says Vardi, suggesting that the treatment encourages blood vessel growth, as found in animal studies. The research team is now in the midst of a new series of tests, which will measure any placebo effect.

“We have done 20 patients more and after a few months the results are approximately the same,” the doctor relates, stressing that such a treatment wouldn’t work on men with muscle or nerve problems, but on those whose erectile problem stems from reduced blood flow.

Shock waves grow blood vessels, treat pain

While commercializing the procedure could be a possibility, Vardi wants to concentrate on the science. But as a researcher and physician with decades of experience, he states, “… I have no question that there is something real in [this new therapy] and that it is important.”

This is the first time that low-dose shockwaves have been used to treat erectile dysfunction, although some research indicates that the treatment could also be useful for growing new blood vessels for the heart. The device is used with higher levels of shockwaves to treat shoulder pain in orthopedics patients. The idea of using sound waves to treat erectile dysfunction came to Vardi when he learned that shockwaves were used to treat men with a curvature of the penis known as Peyronie’s disease.

It’s hard to say when a device might be available to the general public, says Vardi, adding that, “First of all we want to test it more and understand better how effective it can be and how long the [effects of] treatment lasts.” Also, while many men currently self-medicate their erectile disorder, the new shock treatment would require medical consultation and would have to be administered by a physician.

Vardi hopes that in the long run the shockwave therapy could be used to diagnose heart disease at an early stage. Since erectile dysfunction appears in the early stages of diabetes, hypertension and heart disease, a flaccid penis could be a red flag indicating a more grave life-threatening disorder.

By Karin Kloosterman
December 27, 2009

An Israeli researcher finds that the device that blasts kidney stones with shockwaves appears to have a restorative effect on the blood vessels of the penis.

 

Treating impotence: Dr. Yoram Vardi, head of the Neuro-Urology Department of Ramban Medical Center.

For the 35 million men in America alone who suffer from impotence, the issue of erectile dysfunction is no joke. Wonder drugs like Viagra and Cialis have rejuvenated many a couple’s sex life, but not without the associated risks of heart attack and adversely affected vision.

New research from Israel presented to the European Society of Sexual Medicine in Lyon, France in November suggests that a “shocking” new therapy might work to reinvigorate the male sexual organ in a very safe and effective manner. So far, the benefits of the treatment appear to be long lasting.

Dr. Yoram Vardi, head of the Neuro-Urology Department at the Ramban Medical center in Haifa, Israel, has found that the same device that uses shockwaves to blast kidney stones appears to have a restorative effect on the blood vessels of the penis.

In an initial study of 20 middle-aged men with erectile dysfunction – an inability to maintain an erection – for more than three years, researchers conducted a series of treatments that comprised three weeks of shockwave therapy administered in two 20-minute sessions each week.

No pain, all gain

The patients were allowed to rest for three weeks and then an additional course of low-dose shockwave treatments, with about 100 bars of pressure per shockwave, was administered over another three-week period, using a device that resembles a computer mouse.

Vardi found mostly consistent results in all 15 of the 20 men who benefited from the therapy. All the men noted a return of erectile functioning around the seven-week mark, and a six-month follow-up found that for 13 of the men, the effects were long lasting, while two will require additional treatments.

“There was no pain or additional side effects within six months,” Vardi tells ISRAEL21c. “There was an improvement [in erectile function]. A huge improvement.”

How does he explain it? “We feel the effect is something biological,” says Vardi, suggesting that the treatment encourages blood vessel growth, as found in animal studies. The research team is now in the midst of a new series of tests, which will measure any placebo effect.

“We have done 20 patients more and after a few months the results are approximately the same,” the doctor relates, stressing that such a treatment wouldn’t work on men with muscle or nerve problems, but on those whose erectile problem stems from reduced blood flow.

Shock waves grow blood vessels, treat pain

While commercializing the procedure could be a possibility, Vardi wants to concentrate on the science. But as a researcher and physician with decades of experience, he states, “… I have no question that there is something real in [this new therapy] and that it is important.”

This is the first time that low-dose shockwaves have been used to treat erectile dysfunction, although some research indicates that the treatment could also be useful for growing new blood vessels for the heart. The device is used with higher levels of shockwaves to treat shoulder pain in orthopedics patients. The idea of using sound waves to treat erectile dysfunction came to Vardi when he learned that shockwaves were used to treat men with a curvature of the penis known as Peyronie’s disease.

It’s hard to say when a device might be available to the general public, says Vardi, adding that, “First of all we want to test it more and understand better how effective it can be and how long the [effects of] treatment lasts.” Also, while many men currently self-medicate their erectile disorder, the new shock treatment would require medical consultation and would have to be administered by a physician.

Vardi hopes that in the long run the shockwave therapy could be used to diagnose heart disease at an early stage. Since erectile dysfunction appears in the early stages of diabetes, hypertension and heart disease, a flaccid penis could be a red flag indicating a more grave life-threatening disorder.

Texas State agrees to destroy more than 5 million stored blood samples from newborns


Destruction of samples stored for possible medical research ends lawsuit against state.

By Mary Ann Roser

AMERICAN-STATESMAN STAFF

To settle a lawsuit, the state has agreed to destroy more than 5 million blood samples from newborns that it had stored indefinitely for possible research without parents’ consent, the two sides said Tuesday.

The Texas Civil Rights Project filed the lawsuit in U.S. District Court in San Antonio in March on behalf of four parents and a pregnant woman who dropped out later. It claimed that the state’s collection and storage of the samples amounted to “an unlawful search and seizure” and violated the privacy rights of the parents and their children. Under the settlement, the state will destroy 5.3 million samples it has collected between 2002, when the Department of State Health Services began storing the blood, and May 27, when a new state law restricting the practice was signed.

Federal Judge Fred Biery approved the settlement agreement Dec. 14 and gave the state 120 days — until April 13 — to finish destroying the samples, which are stored at Texas A&M University’s School of Rural Public Health.

This year, when stories in the American-Statesman brought the practice to light, the state health department and some medical researchers defended it, saying that collecting the blood spots on paper — done when newborns are screened for various health disorders — might one day provide valuable clues about childhood cancer and other diseases. They said that because the samples were coded and did not identify the babies by name, privacy rights were protected.

But the Texas Legislature approved a law in May requiring medical professionals to inform parents or guardians that the blood spots would be collected and stored indefinitely and could be used for research. Parents who objected could send a statement to the state health department, and their child’s samples would have to be destroyed within 60 days. If the parents didn’t do that, the child could upon reaching adulthood.

Between the time the law passed and Nov. 2, about 6,900 Texans have signed forms asking that the state destroy their child’s samples, out of 240,000 children born in that period, department spokeswoman Allison Lowery said. The department is getting 500 to 600 requests a week to destroy samples, she said.

A statement from the state health department said it “believes settling this lawsuit is in the best interest of this program’s core mission to screen all newborn babies in Texas for life-threatening disorders. Newborn screening saves children’s lives, and settling this lawsuit allows us to continue operating this critical program.”

Jim Harrington , director of the nonprofit civil rights group in Austin, said his organization was “very pleased with the way it worked out.”

Harrington said there were only two options to end the lawsuit: destroy the samples or try and go back to 2002 and get consent from all parents. About 400,000 babies a year are born in Texas.

Among the parents who sued was Austin lawyer Andrea Beleno, Harrington’s daughter-in-law. Her son Joaquin Harrington was born in November 2008, and Beleno said she had no idea “in the haze after giving birth” that any blood had been drawn and stored.

“To me, this whole thing was about consent,” she said. “If they had asked me … I probably would have consented. The fact that it was a secret program really made me so suspicious of the true motives, there’s no way I would consent now.”

Harrington said he will work with a legislative committee before the next regular session in 2011 to refine the new law.

He wants the state to divulge what research it is using the samples for and whether anyone is making money from it. He also wants to see how well the “opt out” provision is working.

Many other states do what Texas had been doing, and a consumer group in Minnesota has been fighting the practice there for several years.

“The State of Texas has taken first steps to restoring the genetic privacy rights of Texas children. This is a wonderful Christmas present for Texas citizens,” Twila Brase, president of the Citizens’ Council on Health Care in St. Paul/Minneapolis, said in a statement.

maroser@statesman.com; 445-3619

Hormones in Concert


Multiple hormones act in concert to regulate blood sugar and food intake. The idea has already led to a new diabetes therapy; will it also yield new strategies for obesity?

By Christian Weyer ; Illustrations by Greg Betza

Stepping on the scale each day and diligently recording their caloric intake and body weight in a little booklet, my patients marked the progress and failures of their dieting efforts. It was the mid-1990s and I was working as a medical fellow in endocrinology and metabolism at the University of Düsseldorf Medical Center in Germany. During the day, we optimized insulin therapy in patients with Type 1 or Type 2 diabetes, using modern tools such as new insulin analogs, glucose meters, and insulin pumps. In the evening, I supervised an outpatient obesity clinic. Our department was internationally renowned as an accredited World Health Organization collaborating center, and patients came from far and wide to seek care for their diabetes, and a variety of obesity-related conditions.

In many respects, the work was very successful, at least in the short term. Young patients with Type 1 diabetes, many with early signs of microvascular complications, achieved their target glucose control levels for the first time since diagnosis. Obese patients, after losing 10% or more of their body weight, saw marked improvements in their liver function tests, cardiovascular risk factors, and/or sleep apnea.

But the limitations of our treatment approaches became apparent over the long term. Upon intensifying insulin treatment, most diabetes patients gained weight and many grew frustrated with the unpredictable glucose swings and constant insulin dose adjustments. Likewise, the vast majority of patients in our obesity clinic saw a relentless regain of their body weight.

In the clinical setting, it was not uncommon for doctors to advise their patients to try harder and be more disciplined. After all, with adequate willpower and meticulous tracking of blood sugars and ingested calories, there had to be a way to do better. From a scientific perspective, however, it was quite evident that the root of the problem was far more complex.

I was drawn to endocrinology because I was intrigued by the complexity and elegance with which hormonal signaling systems govern whole-body metabolism and many other vital functions. Most hormones have multiple actions that are well coordinated, and naturally integrated with other hormonal systems. It is, in many respects, the equivalent of individual musicians playing together in a philharmonic orchestra producing the most melodic, beautiful symphonies. Some hormones, such as insulin, thyroid hormone, or cortisol, are “major players,” and their deficiency or excess can result in life-threatening metabolic derangements. Others, such as calcitonin, pancreatic polypeptide, or amylin can be viewed as complementary signals that enhance, or “fine-tune,” a tightly regulated metabolic process. In many cases, the central nervous system (CNS) orchestrates and balances these hormonal interactions, serving as the role of conductor.

Working model of pramlintide/metreleptin mechanism of action, inferred from preclinical and clinical studies with monotherapy and combination therapy.

A number of important discoveries and developments occurred in the mid-1990s that ushered in a new era of endocrinology-based research and treatment approaches for diabetes and obesity. In diabetes, I had followed with great interest the emerging recognition within the medical scientific community that glucose control was governed by a number of glucoregulatory hormones other than insulin. In obesity, the whole field was electrified by a seminal discovery from Rockefeller University. Using positional cloning, Jeff Friedman and colleagues had identified a fat-derived cytokine hormone, called leptin (from the Greek word leptos, for thin). Mice lacking the leptin gene (ob/ob) displayed a slowed metabolism, a marked increase in food intake, and a profoundly obese phenotype. These abnormalities were corrected by replacing the missing hormone. This discovery not only provided scientific evidence that body weight was regulated by a complex biological feedback system, it also pointed to a pivotal role of hormonal signals in body weight regulation. Clearly, in the expanding panoply of existing and newly discovered hormones, leptin looked like a major player.

While the exact roles of leptin and some of the newer, glucoregulatory hormones—amylin and glucagon-like peptide 1 (GLP-1)—were still to be defined, I wondered whether they might be some of the “missing links” that could explain my patients’ struggles with glucose and weight control. The more I immersed myself into the evolving science, the more I felt compelled toward clinical research rather than clinical practice.

In late 1997, I moved to the United States to work as a visiting researcher with the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), in Phoenix, Arizona. For more than 3 decades, the Phoenix branch of the NIDDK had been conducting pioneering studies on the epidemiology and pathophysiology of obesity and diabetes in Pima Indians, a population with the highest reported prevalence rates of both disorders in the world.

With respect to obesity research, our group was world-renowned for its work on energy expenditure (metabolic rate). We conducted a series of short- and long-term studies showing that weight loss was accompanied by a prompt and sustained drop in metabolic rate and leptin levels. Seeing these results firsthand, I was convinced that the weight regain I had seen in many of my patients was not merely due to a lack of willpower, but rather the manifestation of a powerful, neuroendocrine-mediated metabolic compensation—what we call weight loss counterregulation. In other words, as people lose weight, their bodies mount a response to conserve energy and boost appetite to resist further weight loss, and eventually promote weight regain.

Virtually overnight, diabetes became a disease that was not only recognized as a multi-hormonal disorder, but could also be treated as such.

While the line of research I pursued at NIDDK contributed important insights into the pathophysiology of obesity and diabetes, there was little opportunity to translate scientific findings into novel treatment approaches.

In late 2000, I decided to join San Diego–based Amylin Pharmaceuticals, Inc., a company I had followed with interest for several years. Amylin was the only company I was aware of that was exclusively focused on developing peptide hormone therapeutics for metabolic disorders. The company had just submitted a New Drug Application (NDA) for its lead drug candidate pramlintide. It is an analog of amylin, a hormone co-secreted with insulin by β-cells in the pancreas. Amylin had emerged as a possible “partner hormone” to insulin, complementing insulin’s action in postprandial metabolism. It acts as a neurohormone that binds to receptors in the area postrema of the hindbrain. That binding slows gastric emptying via signals from the vagus nerve and suppresses excess glucagon, a hormone that normally raises blood sugar by triggering the release of glucose stores from the liver.1 The net result is a moderation of glucose influx after a meal, to better match the rate of insulin-mediated glucose disposal.

In parallel, the company was conducting early clinical studies with a second peptide hormone candidate. This was exendin-4 (exenatide), a GLP-1 agonist that held great promise in the management of Type 2 diabetes. GLP-1, a hormone secreted by enteroendocrine cells in the gut, had the intriguing and unique ability to stimulate insulin and amylin secretion in a glucose-dependent manner—that is, only when blood glucose levels are above normal levels. Interestingly, it was noticed that both amylin and GLP-1 appeared to act as satiety signals, curbing food intake by sending a neurohormonal signal to the brain to stop eating.

In early 2005, the hard work of many came to fruition, when both first-in-class drug candidates were approved by the FDA. Pramlintide, the amylin analog, became the first novel, noninsulin peptide therapeutic for Type 1 and Type 2 diabetes in over 80 years. It helps address some of the well-known limitations of insulin therapy by reducing the excessive rise in blood sugar after a meal, erratic glucose swings, and insulin-induced weight gain.2 Exenatide became an attractive alternative to injectable insulin for patients with Type 2 diabetes who were no longer able to control their diabetes with oral agents alone. It offered similar glycemic benefits to basal insulin, but with weight loss rather than weight gain, and without the inherent risk of hypoglycemia or the need for meticulous dose adjustments.3 Virtually overnight, diabetes became a disease that was not only recognized as a multihormonal disorder, but could also be treated as such.

Leptin, the once-hailed “magic bullet” for obesity, was suddenly discarded by many pharmaceutical companies as a failed target.

With both of our approved diabetes drugs having the unique attribute of reducing food intake and body weight, we ventured to tackle obesity as our next therapeutic focus. The scientific community was at that point gaining an increased appreciation that food intake and body weight were governed by a complex interplay between various hormonal signals and the brain. However, in stark contrast to the potent glucose-lowering effect of insulin and GLP-1 agonists in diabetes, no single hormonal pathway caused sufficient weight loss to be considered a therapeutic breakthrough. The once-hailed “magic bullet” for obesity, metreleptin, Amgen’s analog of human leptin, had failed to induce meaningful weight loss in people with general obesity, and was suddenly discarded by many pharmaceutical companies as a failed target.

While metreleptin treatment was not effective in inducing weight loss in patients with general obesity, several studies of rare diseases had emerged hinting at leptin’s therapeutic potential in several “low-leptin” states. Steven O’Rahilly and Sadaf Farooqi had identified a handful of children with congenital leptin deficiency caused by a frame-shift mutation in the leptin gene, named “ob.” As with the ob/ob knockout mice, these leptin-deficient (ob/ob) children displayed a voracious appetite and marked, early-onset obesity. Leptin replacement with metreleptin led to a profound reduction in food intake and body weight. Meanwhile, teams led by Phil Gorden from the NIDDK and Abhimanyu Garg from the University of Texas Southwestern, had administered metreleptin to patients with severe lipodystrophy. This rare syndrome, characterized by a severe loss of adipose tissue and a leptin deficiency, commonly manifests with extremely high circulating lipids, marked insulin resistance, and diabetes that is difficult to control even with very high doses of insulin. Metreleptin dramatically improved these metabolic problems in most patients.4 In a third example of patients with a “low-leptin state,” Christos Mantzoros and colleagues from Harvard demonstrated that metreleptin therapy was able to restore normal ovulatory menstrual cycles in female athletes whose menstrual cycle had stopped because of very low body fat (a syndrome called hypothalamic amenorrhea). Perhaps most relevant to the problem of weight regain in obesity, Rudy Leibel and Michael Rosenbaum from Columbia University showed that using metreleptin to restore normal leptin levels in people who had lost 10% of their body weight almost completely mitigated the counterregulatory responses that drive weight regain.5

As these academic clinical studies with leptin were progressing, we had established our own internal obesity research program. Rather than focusing on single-hormone pathways, we embarked on a comprehensive preclinical program in diet-induced obese rats that tested various dual- and triple-hormone combinations. Our overarching notion was that in normal physiology, food intake and body weight were not regulated by a single, predominant hormonal signal, but rather by a sophisticated interplay of hormonal signals emanating from fat cells (e.g. leptin), β-cells of the pancreas (e.g., amylin) and from cells in the gut (e.g., PYY3–36). With our team of biologists and peptide chemists, we began to systematically modify the native hormones to identify proprietary analogs that were more potent and efficacious than their naturally occurring counterparts.

The initial results from these preclinical studies were stunning to us. While most of the individual hormones induced modest weight loss, we discovered profound, additive, and even synergistic reductions in body weight when testing various dual- and triple-hormone combinations. Moreover, we identified various hormone analogs that achieved marked weight loss even when given alone. With several regimens, we could essentially normalize body weight in obese rodents. While we realized the complexities of translating these results into pharmaceutically tractable interventions, we sensed that we were onto something big. We coined the acronym INTO, for Integrated Neurohormonal Therapy for Obesity, to describe our new obesity research strategy.6

Among the most striking discoveries was a synergistic interaction between amylin and leptin. When given alone, leptin did not reduce body weight in obese rats, but after combining it with amylin, we saw a synergistic effect that led to marked, sustained, fat-specific weight loss (see graphic).7,8 We reasoned that if these results would translate to human obesity, combined treatment with amylin and leptin receptor agonists (i.e., pramlintide + metreleptin) could have tremendous potential.

Though work remains to be done, our findings provide solid clinical proof-of-concept for pairing hormones that are naturally involved in the regulation of food intake and body weight.

In early 2006, Amylin licensed the exclusive rights to leptin from Amgen. Later that year, we initiated our first clinical proof-of-concept study testing the pramlintide/metreleptin combination in approximately 180 overweight and obese volunteers. All subjects followed a strict low-calorie diet for 4 weeks, then were randomized to treatment with pramlintide alone, metreleptin alone, or the pramlintide/metreleptin combination. The stakes were high. Would leptin finally show a clear weight-loss effect, after a dozen or so failed clinical trials?

In late 2007, we unblinded our study and were thrilled to find that our hypothesis on the benefits of combination therapy with pramlintide/metreleptin had borne out in humans. Overweight and obese study participants who completed 20 weeks of combination treatment (after 4 weeks on a low-calorie diet) with pramlintide/metreleptin had lost an average of 13% (>25 lbs) of weight, far more than those receiving pramlintide or metreleptin alone.9 Earlier this year, we confirmed and expanded our findings in a second, larger Phase 2b clinical trial (without an initial period of time on a low-calorie diet) in approximately 600 subjects, showing that pramlintide/metreleptin worked best in obese individuals with mild-to-moderate obesity. In those patients, weight loss with pramlintide/metreleptin again exceeded 10% over 28 weeks, with the vast majority of weight loss being attributable to a reduction in fat mass (approximately 20 lbs).10

Additional studies in larger patient populations are required before the therapeutic potential of the pramlintide/metreleptin combination can be fully assessed. For now, our findings provide solid clinical proof-of-concept for our strategy of pairing hormones that are naturally involved in the regulation of food intake and body weight, and which may have complementary and/or synergistic interactions.

When reflecting on the aforementioned development programs in diabetes and obesity, a number of commonalities emerge. It has become abundantly clear that body weight and glucose metabolism are both regulated by a complex interplay of multiple hormones. Understanding the interaction among these hormones, and combining hormonal signals that have additive or synergistic interactions, can lead to innovative therapeutic approaches. This concept is exemplified by amylin agonism (with pramlintide), which has been successfully developed as an adjunctive therapy to insulin for the treatment of diabetes, and has now also shown promise as an adjunctive therapy to leptin for the treatment of obesity.

While it will take years or decades before the therapeutic utility of peptide hormones in obesity are fully realized, I firmly believe that endocrine solutions will become an integral part of future treatment paradigms.

Christian Weyer, MD is the vice president of Medical Development at Amylin Pharmaceuticals, Inc.

References

1. J.D. Roth et al., “Implications of amylin receptor agonists: integrated mechanisms and therapeutic applications,” Arch Neurol, 66:306-10, 2009.

2. C. Weyer et al., “Amylin replacement as an adjunct to insulin therapy in type 1 and type 2 diabetes mellitus: A physiological approach towards improved metabolic control,” Current Pharm Design, 7:1353-73, 2001.

3. J.L. Iltz et al., “Exenatide: An incretin mimetic for the treatment of type 2 diabetes,” Clinical Therapeutics, 28:652-65, 2006.

4. E.A. Oral et al., “Leptin-replacement therapy for lipodystrophy,” N Engl J Med, 346:570-8, 2002.

5. M. Rosenbaum et al., “Low-dose leptin reverses skeletal muscle, autonomic, and neuroendocrine adaptations to maintenance of reduced weight,” J Clin Invest, 115:3579-86, 2005.

6. H. Chen et al., “Role of islet-, gut-, and adipocyte-derived hormones in the central control of food intake and body weight: Implications for an integrated neurohormonal approach to obesity pharmacotherapy,” Current Diabetes Reviews, 4:79-91, 2008.

7. J. Trevaskis et al., “Amylin-mediated restoration of leptin responsiveness in diet-induced obesity: Magnitude and mechanisms,” Endocrinology, 149:5679-87, 2008.

8. J.D. Roth et al., “Leptin responsiveness restored by amylin agonism in diet-induced obesity: Evidence from nonclinical and clinical studies,” Proc Natl Acad Sci U S A, 105:7257-62, 2008.

9. E. Ravussin et al., “Enhanced weight loss with pramlintide/metreleptin: An integrated neurohormonal approach to obesity pharmacotherapy,” Obesity, 17:1736-43, 2009.

10. “Amylin Pharmaceuticals announces positive results from dose-ranging clinical study of pramlintide/metreleptin combination treatment for obesity,” Amylin Pharmaceuticals press release, July 9, 2009; available online at http://phx.corporate-ir.net/phoenix.zhtml?c=101911&p=irol-news

The Scientist
Volume 23 | Issue 12 | Page 34

The year ahead for Israeli Biotech


Here are five major trends in the sector.
Gali Weinreb
2010 opens with a sense of optimism ahead a transition to a post-crisis era following a mixed year for the Israeli biomedical industry. There are five major trends in the biotechnology industry for 2010.1. Capital is back, but there is less of it.

The year from late 2008 through late 2009 was mainly characterized by uncertainty. Consequently, investment institutions did not transfer money to venture capital funds, which feared to spend what they already had and kept the money for their current portfolio companies. Financing rounds at the same or lower values than previous rounds were widespread.

In 2010, wallets are expected to open, and the first signs have already seen in other countries in the past few months. Financial institutions have to invest in something, and venture capital has actually not disappointed of late.

Venture capital funds also have to invest in new companies in order to revive the dream; after all, it the funds’ raison d’etre. It is doubtful if the funds will be able to raise new capital quickly, but at least they will funds previously committed.

However, the level of investment of 2007, the best year in the history of biomedical investment, is unlikely to be repeated.

The appetite for biomedical investment is also affected by normal macroeconomic conditions, not just those related to crises, such as lengthy development periods, mergers among potential buyers of portfolio companies, and the ongoing absence of a primary market for IPOs.

The Nasdaq revival

After a prolonged drought on the Nasdaq primary market, IPOs resumed during the fourth quarter, including offerings by some fairly new biomedical companies. A large number of companies have published prospectuses, and are now waiting for the right signals from the financial market.

Experts assert that 2010 will be better than 2009, but that’s not hard. There was not a single IPO by a biomedical company between September 2008 and September 2009.

The Tel Aviv Stock Exchange (TASE) also has a number of pending prospectuses for IPOs. Only one biomedical company has held an IPO since the start of the crisis: D-Pharm Ltd. (TASE: DPRM), in August. The drug development company held its IPO at a company value of $30 million before money, a low value for a company undergoing Phase III clinical trials. The share has since soared to give a current market cap of NIS 553 million.

Although the market is interested in IPOs at low prices by potentially fantastic biomedical companies, it is not certain that there will be any such offerings.

3. TASE moment of truth

No young TASE-listed biomedical company went out of business in 2009, although two turned into stock market shells: Topspin Medical Inc. (TASE:TOPMD) and Elutex Ltd. (TASE:ELTX), and neither case was directly related to the economic crisis.

The crisis crowded and strangled many young TASE-listed biomedical companies. In the past two quarters, there were a range of offerings based on shelf prospectuses, as well as rights offerings. Currently, almost all the companies have the wherewithal to survive through the end of 2010. The exceptions are TRD Instrum Ltd. (TASE:TRD), and Intercure Ltd. (TASE:INCR), which will have to offer plans for raising additional capital.

Young TASE-listed biomedical companies will face an interesting year, especially companies with negligible sales and heavy losses. They managed to raise capital over the past year and to survive, perhaps in the hope that the end of the crisis will solve their problems. If they cannot prove themselves in a normal year, they probably won’t get another chance.

4. More exits

After two waves of exits in December 2008 and December 2009, there is no reason for mergers and acquisitions by large and mid-sized pharmaceutical and medical equipment companies to stop. The return of the IPO alternative may even raise prices a bit, albeit Israeli exits are already at good prices.

During 2010, companies such as Pfizer Inc. (NYSE: PFE; LSE: PRZ), Roche AG (SWX: RO), and Merck Inc. (NYSE: MRK) will continue to digest their acquisitions of Wyeth, Genentech, and Schering Plough, respectively. However, huge acquisitions won’t prevent these giants from making smaller buys; they have deep enough pockets.

The question will be how many of the projects acquired by the large companies will be able to be brought to advanced clinical trials, in which the big money is invested. The ability to move forward will determine the milestone payments that the Israeli companies will get.

5. Waiting for the biomed fund

In March 2010, the winners of the government biomed fund will be announced. The optimistic scenario holds that there will be three winners, each of which will manage a $100 million fund.

The introduction of such a large amount of money at one shot could set off shockwaves in the industry, especially if most of the money goes to pharmaceutical and biotechnology companies, as the tender requires. Such inflation could raise company values and might encourage the founding of new start-ups which otherwise would not exist.

The question is whether this money will succeed at the funds’ primary goal, which is to support late-stage companies by providing an alternative to external deals at low prices. This remains to be seen.

Published by Globes [online], Israel business news – www.globes-online.com – on December 24, 2009

© Copyright of Globes Publisher Itonut (1983) Ltd. 2009

Novartis acquires marketing rights for novel broad-spectrum antibiotic


Novartis has signed an agreement with Paratek Pharmaceuticals that entitles Novartis to the worldwide rights to market PTK0796 — a novel broad-spectrum antibiotic capable of fighting multidrug-resistant bacterial infections. The agreement involves an upfront payment of an undisclosed amount from Novartis, with Paratek eligible to receive a total of US$485 million, including milestone payments. The companies will share the responsibility and costs for the development of PTK0796.

The increasing prevalence of multidrug-resistant bacterial strains, together with the decline in the discovery and development of new antibiotic classes, has made the effective tre

atment of many bacterial infections increasingly difficult. “Such multidrug-resistant organisms pose particular challenges in hospital environments,” explains Professor Richard Wenzel, Virginia Commonwealth University, USA. “Efficacy, an oral regimen, and single daily dosing are desirable characteristics for novel antibiotics, but the ability of these organisms to acquire resistance genes readily, the high level of environmental contamination, inadequate infection control and the limited pipeline of antibiotics severely hamper these goals,” he adds. “There is an urgent need for the identification of new antimicrobial targets and the development of new antibiotics with few side effects,” says Professor Robert Daum, University of Chicago Medical Centre, USA.

In this context, studies of PTK0796 — the first in a new aminomethylcycline class of antibiotics, the activity of which is linked to inhibition of bacterial protein synthesis — are so far encouraging. PTK0796 exhibits potent, broad-spectrum activity against a wide range of bacteria and, most importantly, “…appears to be active against many antibiotic-resistant pathogens, such as methicillin-resistant Staphylococcus aureus (MRSA) infections, that have been occurring in epidemic numbers in the United States” notes Daum. Indeed, in a Phase II study involving 200 patients with complicated skin and skin structure infections (cSSSI), in which approximately 50% of the infecting bacteria were MRSA, once-daily oral or intravenous PTK0796 treatment for 14 days achieved a clinical success rate of 98%, with the drug meeting primary safety and tolerability end points. “The availability of PTK0796 in both oral and parenteral forms suggests that transition from parenteral treatment to an oral treatment phase may be performed easily,” says Daum. This may offer a convenient way for patients to continue antibiotic treatment after leaving the hospital.

However, there are some potential limitations to the application of PTK0796. “In the case where the pathogen is known, health-care providers will prefer to narrow the antimicrobial treatment spectrum to accurately target the causative bacterium. Additionally, previous tetracycline derivatives have not been suitable for children younger than 9 years of age, as they tend to accumulate in teeth and bones, raising concern about unsightly cosmetic defects,” notes Daum.

“Although PTK0796 would not solve all the problems due to burgeoning antibiotic-resistant infections, it could be an interesting addition to the anti-infective armamentarium. Further developmental activities should be conducted to identify its niche,” concludes Daum. PTK0796 is currently in Phase III clinical trials for cSSSI, and clinical trials for a number of other potential indications are under way.

Alcon buys Israeli glaucoma treatment co Optonol


The deal with the US eye care company could be worth hundreds of millions of dollars.
Gali Weinreb
Israeli glaucoma treatment company Optonol Ltd. has been acquired by US eye care company Alcon (NYSE: ACL) in a deal potentially worth hundreds of millions of dollars.optonolOptonol will receive an initial cash payment of $150 million for its Ex-Press mini-glaucoma shunt family of products for glaucoma filtering surgery. Milestone payments could earn the company, which is headquartered in Kansas City and has its development center in Neve Ilan near Jerusalem, hundreds of millions of dollaalconrs.

Optonol was founded in 1996 as a spin-off of Jerusalem-based stent developer Medinol Ltd. by CEO Yaron Ira and Benad Goldwasser. The two remain major shareholders in the company, which has raised $30 million, mainly from venture capital funds, over the years. The company’s most recent round of fund raising was for over $20 million from Israel Healthcare Ventures, which owns 13% of the company, and Pitango, which owns 30%. Other well known shareholders in the company include former Likud MK Naomi Blumenthal, Mizrahi Tefahot Bank (TASE:MZTF) CEO Eli Yones and IDB Holding Corp. (TASE:IDBH) co-CEO Avi Fischer.

Optonol’s flagship Ex-Press product is a novel miniature surgical implant used to lower intraocular pressure (IOP) in patients with glaucoma. The company has annual revenue of several million dollars.

Alcon’s VP pharmaceutical products said, “This transaction demonstrates Alcon’s strong commitment to providing physicians with comprehensive treatment options for patients with glaucoma, the world’s second leading cause of blindness. This surgical procedure provides incremental surgeon and patient benefits over traeculectomy, which is currently considered the standard of care in glaucoma surgical therapy.”

The closing of the acquisition is subject to customary closing conditions and the receipt of required regulatory approvals and is expected to occur by the end of the first quarter of 2010.

Published by Globes [online], Israel business news – www.globes-online.com – on December 14, 2009

© Copyright of Globes Publisher Itonut (1983) Ltd. 2009

Pfizer Acquires a Stem-Cell Therapy from Athersys


By ANDREW POLLACK

Pfizer said Sunday that it was buying the rights to a somewhat controversial cell therapy from Athersys, a biotechnology company — a sign of big pharmaceutical companies’ growing interest in stem cells.

Pfizer will have the rights to develop Athersys’s cells to treat inflammatory bowel disease, the companies are expected to announce on Monday. It will pay Athersys $6 million initially and up to $105 million in the future.

The relatively small payment reflects that “it’s really early for cell therapy and there’s more research to be done,” said Ruth McKernan, chief scientific officer of Pfizer Regenerative Medicine, a unit created by the company about 18 months ago to develop treatments based on stem cells.

Athersys’s cells, derived from human bone marrow, have not yet been tested in people with inflammatory bowel disease, a term that encompasses ulcerative colitis and Crohn’s disease. But the product, called MultiStem, is in early human testing as a treatment for heart attacks and for cancer patients receiving bone marrow transplants.

Athersys, founded in 1995 and based in Cleveland, is publicly traded and still unprofitable. Its shares closed at $1 on Friday.Pfizer

Stem cells can form different types of tissue in the body. Pfizer and Athersys envision the cells being infused into patients not to replace damaged tissue but rather to produce various proteins that would help existing tissues heal or prevent them from being damaged.

Stem cells derived from adult tissues, like MultiStem, are less ethically controversial than stem cells from human embryos. But MultiStem has been dogged by scientific controversy.

The cells were initially developed at the University of Minnesota, which said they were multipotent adult progenitor cells — almost as versatile as embryonic cells. But some scientists had trouble replicating those findings, and some papers published by the Minnesota researchers were retracted or corrected.

Dr. McKernan said that those controversies were “in the past now” and that scientists have been able to replicate the findings.

Big pharmaceutical companies have been cautious about stem cells because of the ethical controversies and the early stage of the research. Also, some cell-based therapies must be tailored to each patient, a departure from the business model of producing one-size-fits-all pills.

But as the science of stem cells has advanced, drug companies are taking an interest.

Pfizer is also developing a stem-cell treatment for macular degeneration, an eye disease, working with University College London. It is doing research with Novocell, a San Diego company trying to turn embryonic stem cells into insulin-producing cells to treat diabetes.

Novo Nordisk is working with Cellartis on stem-cell treatments for diabetes. Johnson & Johnson has invested in Novocell and Tengion, another regenerative medicine company. GlaxoSmithKline is providing $25 million to Harvard’s stem-cell institute. And Novartis and Roche have invested in Cellerix, a Spanish stem-cell company.

Myriad Pharmaceuticals to Acquire Javelin Pharmaceuticals


Creates Pipeline With Potential Near-Term Product Launch of Dyloject(TM) and Portfolio of Early-, Mid- and Late-Stage Drug Candidates in Cancer,  HIV and Pain

SALT LAKE CITY, UT and CAMBRIDGE, MA, USA | Myriad Pharmaceuticals (Nasdaq:MYRX) today announced the company has entered into a definitive agreement to acquire Javelin Pharmaceuticals (NYSE Amex:JAV). The acquisition augments Myriad’s portfolio of product candidates with Dyloject(TM) (diclofenac sodium for injection), a New Drug Application (NDA)-submitted candidate with the potential, based on its safety and efficacy profile, to become a valuable addition to hospital formularies as an injectable NSAID for the multimodal management of moderate-to-severe postoperative pain.javelin

Under the Agreement and Plan of Merger, Myriad Pharmaceuticals will acquire all of the outstanding shares of Javelin common stock in exchange for Myriad Pharmaceuticals stock, resulting in the Javelin stockholders owning approximately 41% of the combined company immediately after the closing. The ownership interest of Javelin shareholders may increase up to a maximum of approximately 45% depending upon the timing of FDA approval of Javelin’s lead drug candidate Dyloject. The transaction is expected to close in the first quarter of 2010. Concurrent with the closing of the transaction, Myriad Pharmaceuticals’ board of directors may be expanded to eight members, including up to two members to be nominated by Javelin.

“We believe that this transaction represents a highly effective vehicle to unlock the long-term potential of Myriad Pharmaceuticals and near-term value of Javelin Pharmaceuticals,” commented Adrian Hobden, Ph.D., President and Chief Executive Officer of Myriad Pharmaceuticals. “Myriad is well positioned to successfully launch Dyloject upon FDA approval by leveraging our financial resources and the expertise of our core commercial team. In turn, we believe that potential Dyloject revenue will support the development of our existing clinical stage drug candidates MPC-4326, Azixa, and MPC-3100.”

Martin Driscoll, Chief Executive Officer of Javelin Pharmaceuticals, added, “This agreement creates a fully integrated biotechnology company with a submitted NDA for approval of a specialty care product, Dyloject, backed by significant financial resources, a broad pipeline for growth, and a seasoned management team for future commercialization efforts.”

An NDA for Dyloject was submitted by Javelin on December 2, 2009. Dyloject is an injectable formulation of diclofenac. The development package includes data from two positive Phase 3 studies in postoperative abdominal and orthopedic pain together with safety data accrued from greater than 1,300 patients.

Diclofenac, a member of the class of drugs known as non-steroidal, anti-inflammatory drugs, or NSAIDs, is widely prescribed as an oral treatment for postoperative pain due to its combination of efficacy and tolerability. There remains an underserved medical need in the hospital setting for injectable NSAIDs that are safe, effective and fast-acting in patients unable to take oral medications. Effective use of injectable NSAIDs offers the potential to reduce opioid use and thereby accelerate patient recovery and shorten hospitalization. There is a growing demand for alternatives to opioids in the management of postoperative pain.

“Dyloject has demonstrated a very exciting profile in controlled studies showing statistically significant results in two registration trials, which have been submitted to the FDA for approval consideration earlier this month,” said Ed Swabb, Chief Medical Officer of Myriad Pharmaceuticals. “If approved, Dyloject will be an important tool in the therapeutic armamentarium for multimodal management of postoperative pain.”

Dyloject is approved and marketed in the United Kingdom by Therabel Pharma N.V. Myriad Pharmaceuticals will assume all rights to future milestone payments and royalties due from Therabel Pharma N.V.

About the Combined Pipeline

Myriad expects that, after commercial launch, Dyloject’s revenues will help support development of Myriad’s pipeline of promising clinical candidates, including:

* MPC-4326, a first-in-class small molecule inhibitor of HIV-1 maturation in Phase 2 studies for the oral treatment of HIV infection;

* Azixa(TM), a Phase 2 drug candidate being developed for the treatment of advanced primary and metastatic tumors; and

* MPC-3100, a fully synthetic, orally bioavailable inhibitor of Hsp90 in Phase 1 testing for the treatment of cancer.

Transaction Terms

Under the terms of the definitive merger agreement, Javelin shareholders will receive 0.282 shares of Myriad stock for each share of Javelin stock outstanding, representing a 16.8% premium over the average closing price of Javelin stock over the last 10 trading days. At the time of closing, Myriad will issue shares of common stock to Javelin shareholders representing approximately 41% of the fully diluted ownership of the combined company. Additional shares of common stock, representing approximately 4.1% of the fully diluted ownership of the combined company, will be placed in escrow and may be delivered, in whole or in part, to the pre-merger shareholders of Javelin, depending on the timing of FDA approval of Dyloject prior to June 30, 2011 as follows:

* If approval of Dyloject is received on or before June 30, 2010, the exchange ratio will be increased to 0.3311, representing a 37.1% premium over the average closing price of Javelin stock over the last 10 trading days.

* If approval of Dyloject is received after June 30, 2010, but before January 31, 2011, the exchange ratio will be increased to 0.3066, representing a 27% premium over the average closing price of Javelin stock over the last 10 trading days.

* If approval of Dyloject is received after February 1, 2011, but before June 30, 2011, the exchange ratio will be increased to 0.2943, representing a 21.9% premium over the average closing price of Javelin stock over the last 10 trading days.

* If approval of the Dyloject is received after July 1, 2011, the exchange ratio will remain 0.282, representing a 16.8% premium over the average closing price of Javelin stock over the last 10 trading days.

The boards of directors of both companies have unanimously approved the proposed transaction, which is subject to customary closing conditions, including receipt of required shareholder approvals of both companies.

Concurrent with the signing of the definitive agreement, the companies have entered into a loan and security agreement whereby Myriad will provide up to $6 million of interim financing to fund Javelin’s operating activities prior to closing, which is expected to occur during the first quarter of 2010.

Deutsche Bank Securities Inc. acted as financial advisor to Myriad Pharmaceuticals, Inc. in connection with the transaction. UBS Investment Bank acted as financial advisor to Javelin Pharmaceuticals, Inc.

About Myriad Pharmaceuticals

Myriad Pharmaceuticals, Inc. is a biotechnology company focused on discovering, developing, and commercializing novel small molecule drugs that address severe medical conditions, including cancer and HIV infection. Our pipeline includes clinical and pre-clinical product candidates with distinct mechanisms of action and novel chemical structures that have the potential to be first-in-class and/or best-in-class therapeutics.

About Dyloject:

Dyloject is an injectable formulation of diclofenac with a submitted NDA awaiting filing by the FDA in the United States. Dyloject is already marketed in the United Kingdom. Diclofenac is a prescription NSAID that is widely prescribed to treat postoperative pain. Dyloject has the potential to provide an attractive alternative to other NSAIDs for the management of acute moderate-to-severe pain as a single agent, and to decrease the need for morphine or other opioids in this setting. There exists an underserved medical need for safe and effective injectable NSAIDs.

NSAIDs are widely used postoperatively with opioids, e.g., morphine, to reduce opioid requirements by 30-60% and thereby decrease opioid-related side effects. Combining different types of pain medicines (called “multimodal analgesia”) is the most commonly advocated approach to acute postoperative pain management worldwide. Numerous studies of multimodal analgesia have shown that when patients are given an NSAID along with an opioid, dose requirements and adverse effects of the latter are reduced. Opioid side effects that are reduced by this dose-sparing approach include nausea, vomiting and inadequate breathing.

About Javelin Pharmaceuticals

With corporate headquarters in Cambridge, MA, Javelin applies innovative proprietary technologies to develop new drugs and improved formulations of existing drugs to target unmet and underserved medical needs in the pain management market. The company has one marketed drug in the U.K., an NDA-submitted drug candidate, Dyloject, and two drug candidates in U.S. advanced clinical development.

About MPC-4326:

MPC-4326 is being developed by Myriad Pharmaceuticals, Inc. for the oral treatment of HIV-1 infection. MPC-4326 is the first of a class of antiretroviral (ARV) drug candidates that inhibit HIV-1 replication by interfering with the maturation of the HIV-1 virus. Specifically, MPC-4326 interferes with the last step in the processing of the HIV-1 Gag protein. This inhibition leads to formation of noninfectious, immature virus particles, thus preventing subsequent rounds of HIV infection. As expected for a novel mechanism of action, MPC-4326 retains inhibitory activity against HIV-1 isolates resistant to the four classes of currently approved drugs commonly used by HIV infected patients: NRTIs, NNRTIs, protease inhibitors and fusion inhibitors. No cross-resistance has been observed.

Over 675 subjects, including over 180 HIV-infected individuals, have been studied in clinical trials of MPC-4326. Results from these trials have shown MPC-4326 to be well-tolerated and have demonstrated significant and clinically relevant reductions in viral load in a subset of HIV-infected patients representing approximately 60-70% of HIV-infected patients. This “responder” population can be identified by a simple, rapid and inexpensive assay of the HIV virus. In a Phase 2 clinical trial completed in 2008, MPC-4326 met its primary objective by demonstrating viral reduction in HIV-positive patients. In addition, the safety profile of MPC-4326 was comparable to earlier studies where that profile had been similar to placebo.

About Azixa (MPC-6827):

Azixa, MPI’s most advanced cancer drug candidate, is being developed for the treatment of advanced cancers with brain involvement. Azixa is a novel small molecule that acts as a microtubule destabilizing agent, causing an arrest of cell division with subsequent programmed cell death, or apoptosis, in cancer cells. Several currently marketed clinically effective drugs share the identical mechanism of action. Importantly, however, Azixa has two unique, distinguishing characteristics. In non-clinical studies, Azixa has demonstrated the ability to effectively cross the blood-brain barrier and accumulate in the brain at levels as much as 3000% that in plasma. In addition, Azixa does not appear to be subject to multiple drug resistance (MDR) mechanisms.

Myriad Pharmaceuticals believes that Azixa represents a unique therapeutic opportunity with the potential to treat patients with any primary or secondary (metastatic) brain cancer or any cancer that has developed resistance to conventional chemotherapeutics. Azixa is currently in clinical studies in patients with glioblastoma multiforme and metastatic melanoma.

About MPC-3100:

MPC-3100 is currently in Phase 1 clinical studies. MPC-3100 is a novel, fully synthetic, orally bioavailable, small-molecule inhibitor of Heat shock protein 90 (Hsp90). Hsp90 is a proven target for cancer treatment. Early natural product inhibitors of Hsp90 demonstrated activity in several human cancer clinical studies, including studies of Her2+ breast cancer, multiple myeloma and gastric cancers. However, these compounds have also demonstrated significant toxicity. Unlike these molecules, MPC-3100 is a fully synthetic, small molecule that is orally bioavailable and has very encouraging non-clinical safety and efficacy data. MPC-3100 has the potential to treat a wide range of cancers.

Myriad Pharmaceuticals has an issued composition of matter patent on MPC-3100 and has developed a tablet formulation. These tablets are being used in the ongoing Phase 1 study. The trial has achieved drug levels in patients which are similar to efficacious levels obtained in non-clinical studies.

Heat shock protein 90 (Hsp90) is a chaperone protein that plays an important role in regulating the activity and function of numerous signaling proteins, or client proteins, that trigger and maintain proliferation of cancer cells. Important client proteins in cancer cells include steroid hormone receptors, protein kinases, mutant p53, and telomerase. Hsp90 binds and stabilizes these oncogenes while inhibition of Hsp90 leads to their degradation.

SOURCE: Myriad Pharmaceuticals, Inc.

Eisai exercises option to acquire AkaRx and its oral TPO agonist


Eisai Obtains Worldwide Rights to Develop, Market and Manufacture AKR-501, Therapeutic Agent for Thrombocytopenia

Tokyo, Japan | Eisai Co., Ltd. (Headquarters: Tokyo, President and CEO: Haruo Naito, “Eisai”) today announced that the Company will initiate procedures to acquire AkaRx, Inc. (Headquarters: New Jersey, U.S., CEO: Robert E. Desjardins, “AkaRx”). As a result of the acquisition, AkaRx will become a subsidiary of Eisai Inc., Eisai’s U.S. subsidiary. The buyout price has been set at US$255 million (approximately ¥22.7 billion, converted yen at 89 to the US$).

Eisai obtained an option right to acquire AkaRx through the Company’s acquisition of MGI PHARMA, INC. (“MGI”) in January 2008, as well as a development and license agreement relating to AKR-501 (current research code: E5501). Eisai has expressed its intention to exercise this option, and will acquire all of AkaRx’s capital stock to make it a wholly-owned subsidiary of Eisai Inc. as well as the exclusive worldwide rights to develop, market and manufacture AKR-501. The Company plans to consummate this acquisition on or before January 8, 2010.

AKR-501 is a pharmacological agonist of the receptors of thrombopoietin (TPO), which stimulates platelet production, and is expected to demonstrate its effects in various diseases associated with thrombocytopenia. Eisai is currently conducting Phase II clinical studies of the compound in the U.S. for idiopathic thrombocytopenic purpura (ITP) and thrombocytopenia associated with liver diseases, and has confirmed POC (Proof of Concept) in the clinical studies for ITP. In addition, Eisai will explore its potential as a treatment for cancer chemotherapy-induced thrombocytopenia.

ITP is a disorder that causes a variety of bleeding symptoms due to a decrease in platelet count caused by the destruction of blood platelets as a result of the production of autoantibodies against platelets. The number of patients with the disorder is estimated to be approximately 800,000 (Japan, U.S., major European countries, China, and India). It is known that, in patients with liver diseases, decrease in platelet count as a complication resulting from deficient TPO production causes bleeding tendency, and in many patients with hepatitis C, interferon-induced thrombocytopenia could lead to the cessation of their interferon therapy. If successfully developed, Eisai expects that AKR-501 will provide a new treatment option for patients with thrombocytopenia, as well as increase its contributions to patients in China, India and other countries with a high incidence of hepatitis.

Through this acquisition, Eisai will further enhance its portfolio of pipeline products, and will make contributions towards increasing benefits of patients and their families by addressing the unmet medical needs.

In accordance with the acquisition, Eisai has revised its full-year consolidated business forecast for the fiscal year ending March 31, 2010, (April 1, 2009 to March 31, 2010) as outlined below.

1. Revised full-year consolidated business forecast for the fiscal year ending March 31, 2010 (April 1, 2009 to March 31, 2010)

(unit: million yen)

Net Sales Operating Income Ordinary Income Net Income
Previous Forecast (A) 820,000 103,000 97,000 63,000
Revised Forecast (B) 820,000 80,300 74,300 40,300
Changes in Amount (B-A) 0 22,700 22,700 22,700
Percentage of Change 22.0 23.4 36.0
(Reference)
Business Results for the fiscal year ended March 31, 2009
781,743 91,808 82,583 47,678

The above revised forecasted figures are based only on the estimation of the impact of the acquisition. No revision has been made to the company’s non-consolidated full year business forecast.

Further information with regards to the full-year consolidated business forecast for the fiscal year ending March 31, 2010 (April 1, 2009 to March 31, 2010) will be announced in the financial report for the third quarter of this fiscal year.

2. Reasons for revision
The Company anticipates that it will incur an in-process research & development expense*1 of US$255 million (approximately ¥22.7 billion*2) in accordance with the acquisition of AkaRx.

*1 The amounts assigned to product candidate compounds under development that have no alternative future use shall be booked as one-time R&D expense.

*2 The amount in yen is based on the most recent currency exchange rate. (converted yen at 89 to the US$)

3. Year-end dividend forecast
In cash-flow, the expense that will occur in association with the acquisition of AkaRx, will be accounted as cash-flow used in investment activities and will not affect cash income,* which expresses the company’s ability to generate cash. Therefore, the full-year consolidated cash income forecast of ¥120 billion (an increase of 0.8% year-on-year) shall remain unchanged.

Accordingly, the year-end dividend forecast of ¥80 per share remains the same as the previous forecast and the annual dividend is expected to be ¥150 per share (an increase of ¥10 from the previous fiscal year).

* Cash income = Net income for this period + Depreciation of property, plant and equipment and amortization of intangible assets + In-process R&D expenses + Amortization of goodwill + loss on impairment of long-lived assets (including loss on devaluation of investment securities).

[Please refer to the following notes for an outline of AkaRx, Inc. and AKR-501 as well as information on ITP and thrombocytopenia associated with liver diseases]

About AKR-501

AKR-501(current research code: E5501) is a pharmacological agonist of the receptors of thrombopoietin (TPO), which stimulates platelet production acting on megakaryocytes and their precursors. When administered orally, this novel compound is expected to demonstrate its effects in various diseases associated with thrombocytopenia by promoting an increase in platelet count. Eisai is currently conducting Phase II clinical studies of the compound in the United States for idiopathic thrombocytopenic purpura (ITP) and thrombocytopenia associated with liver diseases, and has confirmed POC (Proof of Concept) in the clinical studies for ITP.

About Idiopathic Thrombocytopenic Purpura (ITP)

Idiopathic thrombocytopenic purpura (ITP) is a disorder that causes a variety of bleeding symptoms due to a decrease in platelet count caused by the destruction of blood platelets. The number of patients with this disorder is estimated to be approximately 800,000 (Japan, U.S., major European countries, China, and India). ITP can be classified into two types: acute ITP which is common in children and chronic ITP common in adults. It is thought that approximately 5 to 20% of the latter are refractory or intractable to treatment.

About thrombocytopenia associated with liver diseases

It is known that, in patients with liver diseases, decrease in platelet count as a complication resulting from deficient TPO and increased destruction of platelet in spleen associated with portal hypertension causes bleeding tendency. While such patients may undergo a platelet transfusion as a surgical procedure, the development of more useful treatment is anticipated due to difficulty in securing transfusable platelets and risk of infection. In many patients with hepatitis C, interferon-induced thrombocytopenia could lead to the cessation of their interferon therapy.

SOURCE: Eisai

Substance abuse diagnostic test for teens can also predict high risk sexual behavior


 

Alcohol and drug use are known contributors to adolescents engaging in dangerous sexual activity; leading to substantial health risks such as unwanted pregnancies, sexually transmitted illnesses, drug overdoses and alcohol poisonings. Yet, research suggests that fewer than half of pediatricians report screening patients for substance use and at-risk sexual behavior. CRAFFT, the diagnostic test developed and currently being employed at Children’s Hospital Boston, allows primary care physicians to accurately screen teens for high risk drug and alcohol use in a matter of minutes. Now, according to a new study appearing in the Journal of Adolescent Health, Children’s researchers have established that the CRAFFT diagnostic test can also identify teens that are more likely to be engaging in high risk sexual behaviors.

The studies researchers found that teens who screened positive for substance use had significantly greater odds of having sexual contact after using drugs or alcohol. According to the findings, these teens were more likely to have unprotected sex, multiple sexual partners and even a sexually transmitted illness. The cross-sectional survey consisted of 305 adolescents from ages 12- to 18-years-old in 3 different urban clinics. Participants were asked the CRAFFT questions, and also completed a self-administered questionnaire about high risk sexual behaviors. Of those who screened positive, 42.6% reported having sexual contact without a condom, 26.1% after drinking alcohol, 15.6% after drug use and 21.7% with a partner who had been drinking alcohol.

Developed by the Children’s Center for Adolescent Substance Abuse Research, the CRAFFT screen, which refers to the mnemonic acronym in the six screening questions, includes questions such as “do you ever use alcohol or drugs to relax, feel better about yourself, or fit in?” and “do you ever forget things you did while using alcohol or drugs?” Answering “yes” to two or more questions is highly predictive of an alcohol or drug-related disorder and now at-risk sexual behavior.

“Primary care physicians are on the frontline of identifying adolescents who are at-risk and all should be screened with questions like these at every routine medical visit,” says Sharon Levy, MD, co-author of the study and physician in the Adolescent Substance Abuse Program at Children’s. “Clinicians should be prepared to discuss high risk sexual behaviors with their patients along with the dangers of engaging in sexual activity while intoxicated. Something as simple as asking an adolescent a few questions during a clinical appointment might make the difference.”

The CRAFFT test is routinely administered during adolescent clinical appointments at Children’s. All adolescents who take the test receive brief advice on alcohol and drug use, and those who test positive are recommended to further assessment for substance use disorders. The authors suggest that these adolescents also receive counseling to avoid high risk sexual behaviors and sexual activity after alcohol or drug use.

Contact: James Newton
james.newton@childrens.harvard.edu
617-919-3110
Children’s Hospital Boston

BioCrossroads spurs 2nd VC fund


INext Fund has $58M to pump into state life sciences startups

By Tom Spalding
tom.spalding@indystar.com

BioCrossroadsIndiana-bred life sciences startups hoping to commercialize new products will be able to seek help from a second venture capital fund organized by BioCrossroads, a key promoter of the state’s life sciences industry.

The group has secured $58 million for the INext Fund, a successor to the $73 million Indiana Future Fund that was formed six years ago and helped 14 Indiana startups.

The new fund’s goal is to help businesses that specialize in breakthrough medical, pharma and biotech products that need upfront cash necessary for survival and success.

The fund is seeded with money from Eli Lilly and Co., the Indiana State Teachers’ Retirement Fund, Indiana University, Purdue University, Notre Dame and the Richard M. Fairbanks Foundation, an Indianapolis-based independent private foundation that donates to nonprofits.

The hope is to build on the success of the previous fund, which provided capital to companies such as BioStorage Technologies, an Indianapolis-based biomaterials storage and inventory management company.

Since receiving venture funding three years ago, the company has tripled its work force, this year announcing plans to invest $6.1 million in a new facility and to add 125 jobs to its existing 70-associate team by 2012.

“We’ve made incredible progress building a market where (venture capital) firms, both local and out of state, are investing in our promising life sciences companies,” said David Johnson, president and CEO of BioCrossroads, a nonprofit that invests in and supports life sciences.

Launching a second fund shows the state is “serious about building new companies,” said Darren Carroll, vice president of Lilly New Ventures and chairman of INext’s advisory committee. “You have to have a lot of dollars flowing in” to these startups, or they will take their idea — and business — elsewhere.

Given the current challenges in the U.S. economy, “building a return-driven fund of this magnitude is very impressive,” said Phil Belt, who is with the Indianapolis branch of Credit Suisse Customized Fund Investment Group, the fund manager.”

Indiana has seen an increase in the number of entrepreneurial life sciences companies, both university-based and private startups, since the formation of the Indiana Future Fund.

In 2001, Indiana was 36th among the states in terms of attracting venture capital dollars. By mid-2009, it had jumped to 19th. Also, from 2001 to 2003, average annual venture capital investment in Indiana companies was $41 million. From 2004 to 2008, the average annual amount was $145 million, according to the publication Venture Economics.

Officials say the $73 million from the Indiana Future Fund helped bring more than $160 million to Indiana startups from venture capital firms across the U.S.

 

Merck’s CGRP receptor antagonist meets Phase III migraine end points


Merck has announced that the antagonist of the calcitonin gene-related peptide (CGRP) receptor telcagepant has met the primary end points in two Phase III trials to treat migraine, which is characterized by attacks of intense throbbing head pain that can last from 4 to 72 hours.

One study showed that the compound led to significant pain relief compared with placebo 2 hours after treatment and sustained freedom from pain up to 24 hours after treatment. A second study comparing telcagepant with rizatriptan (Maxalt; Merck) — a drug from the triptan class of serotonin receptor agonists, which are currently the standard of care for migraine — showed that fewer patients reported pre-specified adverse events (5% versus 11.2%) when given telcagepant.

The rationale for targeting CGRP receptors is based on two key clinical observations, explains Professor Andrew Russo, Director of the Biosciences Program, University of Iowa, USA. “It was almost 20 years ago that Lars Edvinsson and Peter Goadsby showed that CGRP was elevated in the jugular outflow during severe migraine attacks and that treatment with sumatriptan restored the levels to normal, co-incident with the alleviation of the symptoms. Further work from Jes Olesen’s group then showed that injection of CGRP led to the development of headaches in a small group of migraine patients. These observations point to CGRP being a key neuromodulator that may act by sensitizing glutamatergic synapses in the central nervous system, and that too much sensitization leads to migraine.”

Unlike serotonin receptor agonists, CGRP receptor antagonists do not constrict blood vessels and therefore do not seem to have deleterious cardiovascular side effects. These side effects limit the use of triptans in patients who also suffer from cardiovascular disease or uncontrolled hypertension. “In addition, since these drugs act by different mechanisms, it is likely that telcagepant and other CGRP receptor antagonists will help some patients who are not helped by triptans,” says Russo.

However, Merck is delaying its submission of a new drug application for telcagepant owing to the increased levels of liver transaminases that were observed in patients receiving the drug twice daily for 3 months in a Phase IIa study to prevent migraine. Whether this potential hepatotoxicity signal is a class effect or is specific to this compound, and its relation to the dose and frequency of administration of telcagepant, still need to be elucidated. However, if telcagepant shows comparable efficacy to triptans, with no vasoconstriction and a more tolerable side-effect profile, analysts have predicted that sales could reach more than US$1 billion per year. Recent evidence has also implicated CGRP in tumour angiogenesis (Proc. Natl Acad. Sci. USA 105, 13550–13555; 2008), therefore CGRP antagonists might also have potential in other indications.

Top of page

References

FURTHER READING
  1. Goadsby, P. J. Can we develop neurally acting drugs for the treatment of migraine? Nature Rev. Drug Discov. 4, 741–750 (2005)

GSK and Intercell to Develop Patch-Based Vaccines


GlaxoSmithKline Biologicals SA (GSK, London, UK) and Intercell (Vienna, Austria) have formed a strategic alliance to accelerate the development and commercialization of needle-free, patch-based vaccines. The agreement will include Intercell’s candidate vaccine for travelers’ diarrhea (TD), currently in Phase 3 trials, and an investigational single application pandemic influenza vaccine, as well as the use of the patch technology for other vaccines in GSK’s portfolio.

Compared with standard immunization by needles, the patch technology could offer certain benefits, such as easy administration and direct delivery of the antigen and adjuvant to the immune system through natural defense pathway, which could make vaccination more efficient.

In studies, the patch was shown to boost cellular immunity to a diverse range of antigens and to stimulate both B-cell and T-cell responses. It contains the heat labile enterotoxin from E. coli, one of the most potent stimulators of the immune system.

Intercell’s pandemic influenza patch is designed to enhance the immune response to existing injected pandemic influenza vaccines. If successful, the patch will expand the limited vaccine supplies by allowing fewer or lower doses of vaccine.

When used in a combination with an injected pandemic influenza vaccine (H5N1), the patch enhanced the immune response to the vaccine after only a single dose, resulting in a seroconversion rate of 70%, meeting the FDA and EMEA standard for approval of a pandemic Influenza vaccine. The development of a pandemic influenza vaccine patch has been funded in part by the US Department of Health and Human Services.

Under the terms of the agreement, GSK will make an upfront cash contribution of €33.6 million, in addition to an equity investment of up to €84 million through a staggered shareholding purchase option of up to 5% in Intercell. Included in the agreement are Intercell’s investigational TD vaccine, currently in Phase 3, and an investigational single application pandemic influenza vaccine in Phase 2, as well as other potential future patch vaccines.

Bone Marrow Transplants May Cure Sickle Cell in Adults


By Jennifer Thomas
HealthDay Reporter

Researchers say that a new method of bone marrow transplantation cured nine out of 10 adult patients with sickle cell disease, an inherited condition that causes bouts of severe pain, organ damage and sharply limits life expectancy.

Adults have typically not been candidates because they were thought to be too sick to handle the high doses of chemotherapy and radiation necessary to prep the body for the procedure, explained senior study author Dr. John Tisdale, a senior investigator in the molecular and clinical hematology branch at the U.S. National Institutes of Health.

Until now, transplantation was generally reserved for more resilient children, whose bodies had not yet suffered as much damage from sickle cell disease.

But the new method allows for a less grueling pre-transplantation routine, one that even adults with severe sickle cell can tolerate.

More than 70,000 Americans suffer from sickle cell disease, and it is especially common among blacks. People with the disease have abnormal, crescent-shaped hemoglobin. The abnormal cells have difficulty passing through small blood vessels, causing blockages and damaging tissues. Over time, the damage can lead to stroke and severe bouts of pain in the chest, arms, legs, chest and abdomen. Sickle cell disease also damages the kidneys, liver and spleen, leaving people, especially children, more susceptible to infection, said Dr. Lanetta Jordan, chief medical officer for the Sickle Cell Disease Association of America.

Treatments include prophylactic antibiotics to fight infections, blood transfusions and hydroxyurea, the only drug U.S. Food and Drug Administration-approved drug for treating sickle cell, Jordan said.

In the new study, Tisdale and his colleagues gave 10 patients ages 16 to 45 with severe sickle cell disease alemtuzumab, a drug used to suppress immune system T-cells; relatively low doses of radiation; and sirolimus, an immune suppressant to fight rejection. Marrow donors were siblings with matched HLA (human leukocyte antigen) markers in their blood.

None of the patients experienced graft-versus-host disease, one of the most common and potentially fatal complications of bone marrow transplants, in which the body rejects the new bone marrow.

After 30 months, all of them are alive, and nine of the patients had successful grafts and are considered cured of sickle cell disease, according to the study.

“It’s been transforming for these patients,” Tisdale said. “These were the sickest of the sick patients. Some were in the hospital every other week for pain or other crises. Today, some have gone back to school and to work. One patient had a baby.”

The last item is important, because in conventional bone marrow transplants, high doses of chemotherapy drugs and radiation typically destroy fertility. However, the lower level of radiation used in the new method does not seem to do this.

The study is published in the Dec. 10 issue of the New England Journal of Medicine.

Conventional bone marrow transplants cure sickle cell disease by first using chemotherapy and radiation to wipe out the person’s own marrow, which makes the faulty red blood cells. The marrow is replaced with stem cells from a donor’s marrow, which then takes over and begins to produce new, healthy red blood cells.

But when doing the new bone marrow transplants, the researchers noted that not all of the patient’s own marrow was wiped out. Some remained and seemed to co-exist with the donor marrow without causing problems, Tisdale said.

“That meant we didn’t necessarily have to kill the entire bone marrow of the patient to make this work,” Tisdale said, opening the possibility of using an even less toxic means of preparing the body for transplant.

Though most patients in the study are still taking immune-suppressant drugs, researchers hope to eventually wean them off the medications.

Dr. Miguel Abboud, a pediatric hematology/oncology specialist and a professor of pediatrics at the American University of Beirut Medial Center, in Lebanon, said the new protocol is promising, especially since it could eventually include those who don’t have an HLA-matched sibling.

“The findings are very significant because adults with very severe sickle cell disease have decreased life expectancy and multiple morbidities but have limited therapeutic options,” said Abboud, who wrote an accompanying editorial. “In the past these patients were excluded from transplant studies as they are very poor candidates for high dose chemotherapy regimens. This study makes it possible to offer this subset of patients with severe sickle cell disease stem cell transplants.”

Dr. Lakshmanan Krishnamurti, a pediatric hematologist/oncologist at the University of Pittsburgh and director of the Sickle Cell Program at Children’s Hospital of Pittsburgh, has done bone marrow transplants in children, also using a less toxic protocol.

“This is an important paper and a big step forward for the field,” Krishnamurti said. “Now we are able to say, ‘OK, young adults or not so young adults can be transplanted successfully.’ That is a very big deal.”

AstraZeneca Explores Alliances to Spread Cost, Risks


Dec. 10 (Bloomberg) — AstraZeneca Plc is in “exploratory discussions” with competitors for partnerships that would

Shaun Grady, vice president of corporate business development at AstraZeneca Plc., poses in this undated handout photograph released to the media on Dec. 10, 2009. Source: AstraZeneca

Shaun Grady, vice president of corporate business development at AstraZeneca Plc., poses in this undated handout photograph released to the media on Dec. 10, 2009. Source: AstraZeneca

help ease the cost and risk of developing new medicines, said Shaun Grady, vice president of corporate business development.

“We’re working together to get more out of sharing the risk and sharing the cost,” said Grady, 48, in a Dec. 8 telephone interview from London, where the company is based. “We’re looking across the spectrum, but our focus is late-stage assets. That’s where we can make the most difference with the business shape going forward right now.”

AstraZeneca, Eli Lilly & Co. and Bristol-Myers Squibb Co. are the “worst positioned” to overcome the so-called patent cliff drugmakers will encounter in the next five years, when 9 of the world’s 10 biggest drugs lose market exclusivity, Sanford C. Bernstein analyst Tim Anderson wrote in a Dec. 8 note.

Medicines that generated 62 percent of AstraZeneca’s 2008 revenue face competition from lower-priced copies by 2014, according to Bloomberg data. Its Nexium heartburn drug, ranked eighth among the top-selling drugs in 2008 with $5.2 billion in revenue, will lose patent protection starting next year.

AstraZeneca has stepped up the hunt for new products since paying $15 billion for MedImmune Inc. in 2007, signing three licensing partnerships in the last six months. The most recent was last week’s contract to develop a Targacept Inc. depression drug in a transaction valued at as much as $1.24 billion. The U.K. drugmaker prefers licensing deals to acquisitions and plans to announce at least one more partnership before the end of the year, said Grady.

Diabetes Alliance

The executive pointed to two examples of the type of deal AstraZeneca is looking for: a 2007 partnership with Bristol- Myers Squibb Co. to develop Onglyza, a diabetes medicine that won U.S. approval in July, and a June alliance with Merck & Co. to develop a combination of their cancer-fighting compounds.

The executive declined to give names of potential partners or discuss disease areas in which he sees gaps.

“Each therapy area has its own externalization strategy,” said Grady. “They’ll look at their own assets and if there are gaps or omissions, we tend to keep an eye out. We know what we’re good at and we’re concentrating on areas of strength.”

The company doesn’t plan any “significant foray” beyond its key disease areas, which include cancer, respiratory illnesses and mental illness, Grady said.

The U.K. drugmaker doesn’t have a large vaccine or consumer product unit that rivals GlaxoSmithKline Plc and Sanofi-Aventis SA are relying on to cushion looming patent expirations.

“We don’t look at it in terms of the sales we need to replace,” Grady said. “We believe these projects have a good probability of success and will make a big difference in the short- and near-term.”

 

Last Updated: December 10, 2009 08:52 EST

Stem Cells May Hold Hope for Eye Disease


In study on mice, one type of umbilical cell cleared cloudy corneas

TUESDAY, Dec. 8 (HealthDay News) — New research has found that a certain kind of stem cell from human umbilical cords helped restore transparency to the cloudy corneas of laboratory mice,  raising the prospect that they could do the same for people.

Click here to find out more!

Currently, a limited supply of donated human corneas is available to help people with severe corneal and eye diseases.The new research examined human umbilical cord mesenchymal stem cells. When transplanted into the corneal stroma of the mouse eyes, they survived for more than three months without much sign of graft rejection, researcher Winston Kao of the University of Cincinnati School of Medicine, said in a news release from the American Society for Cell Biology.

Transplantation of human organs involves a certain degree of risk because the body tries to reject things it considers foreign. In the study, that happened to another kind of stem cell — human umbilical hematopoietic stem cells — that was transplanted into the mouse eyes.

However, according to Kao, stem-cell transplants hold promise as a treatment for some eye diseases. He said it’s easy to isolate the cells and let them reproduce before storage, and the supply of stem cells is virtually unlimited.

The findings were to be presented Dec. 8 at the American Society for Cell Biology’s annual meeting in San Diego.

More information

The U.S. National Eye Institute has more on corneal disease.

GSK shops around for $3bn worth of acquisitions


Drugs giant looks to expand in emerging and developed markets
Drugs giant GSK is scouring the globe for acquisitions and could splash out more than $3bn to expand in consumer healthcare, over-the-counter medicines, generics and vaccines.

Analysts say the company is looking at acquiring Dr Reddy’s, the Indian generics firm that has large selling operations in Africa, the Middle East and Latin America. Other targets include Genmab, the Danish biotechnology company, Theravance of the US and Aspen, the South African generics firm.

GSK is keen to expand further in emerging markets, especially India and China, where pharmaceutical groups are keen to strike licensing and marketing agreements with Western rivals.

But there are also opportunities for bolt-on acquisitions. “With a strong balance sheet and a rising share price, GSK could easily afford to pay $3bn or more to extend its international operations,” said Navid Malik, analyst at Matrix Corporate Capital.

Seven emerging nations – Brazil, Russia, India, China, Korea, Mexico and Turkey – could account for 70% of pharma sales growth by 2020, says a UBS study.

But GSK is also making acquisitions in developed countries. Earlier this year it moved to broaden its product range by agreeing a $3.6bn deal to buy skincare specialist Stiefel Laboratories. The agreement is consistent with chief executive Andrew Witty’s strategy of diversifying the company’s portfolio away from conventional blockbuster drugs as patents come to an end on key products.

The Stiefel acquisition, which followed GSK’s deal to form a new HIV company with US rival Pfizer, was significantly smaller than the recent mega-mergers in the sector. These include Pfizer’s $68bn takeover of Wyeth and Merck’s $41.1bn deal for Schering-Plough. Mr Witty has spoken of his opposition to large-scale acquisitions, instead preferring to grow GSK via smaller purchases.

GSK’s sales are also being bolstered by sales of swine flu vaccines, which should add £1bn to revenue this year.

Treanda data could lead to 10-fold sales jump


Journal of Clinical Oncology Publishes TREANDA Study Demonstrating Significant Improvement in Overall Response and Progression-Free Survival in Chronic Lymphocytic Leukemiatreanda

FRAZER, Pa., Aug. 3 /PRNewswire-FirstCall/ — Cephalon, Inc. (NASDAQ: CEPH) today announced that the Journal of Clinical Oncology has published data from a pivotal phase 3 study demonstrating that TREANDA (bendamustine HCl) for Injection improved clinical outcomes when compared to chlorambucil in patients with chronic lymphocytic leukemia (CLL). Results of this study were the basis of the March 2008 U.S. Food and Drug Administration (FDA) approval of TREANDA for CLL, the first agent approved by the FDA for this disease since 2001. According to the American Cancer Society, there will be more than 15,000 new cases of CLL diagnosed in 2009 alone. The study results were published online today and will also appear in the print edition later this year.

This Phase 3, randomized, international, multicenter, open-label study evaluated the efficacy and safety of TREANDA compared to chlorambucil in previously untreated patients with advanced (Binet stage B-C) CLL. Patients received TREANDA (100 mg per square meter on days 1 and 2) (n=162) or chlorambucil (0.8 mg/kg on days 1 and 15) (n=157) for up to six treatment cycles. In this study, TREANDA demonstrated significantly better outcomes for both primary endpoints compared to chlorambucil: overall response rate and progression-free survival (PFS).The overall response rate was significantly higher in patients receiving TREANDA than chlorambucil (68% vs. 31%; p<0.0001). Patients in the TREANDA treatment arm also had a higher complete response rate than those treated with chlorambucil (31% vs. 2%) which means that after treatment with TREANDA, some patients had no signs of CLL in their blood.

“CLL is the most common form of adult leukemia in the Western world. Because it is incurable, the goal of treatment is to stabilize the cancer over the long-term by extending periods of remission,” said Prof. Wolfgang Knauf, Onkologische Gemeinschaftspraxis, Frankfurt, Germany and lead investigator of this study. “Treatment options are limited for those with advanced CLL, but this study shows that bendamustine demonstrates significantly better efficacy compared to chlorambucil with a tolerable safety profile.”

The study also showed that patients treated with TREANDA had significantly longer PFS compared to chlorambucil (median PFS 21.6 months vs. 8.3 months; p<0.0001). TREANDA was also associated with an improvement in duration of response compared to chlorambucil (21.8 months vs. 8 months). In the study, TREANDA demonstrated a tolerable safety profile; the most common adverse events included myelosuppression, fever, nausea, vomiting and diarrhea. The Clinical Studies section of the TREANDA prescribing information includes complete FDA-approved study information.

About TREANDA

TREANDA, a novel chemotherapy, was approved by the FDA for the treatment of CLL in March 2008. Efficacy relative to other first line therapies other than chlorambucil has not been established. TREANDA received its second approval in October 2008 for the treatment of patients with indolent B-cell non-Hodgkin’s lymphoma (NHL) that has progressed during or within six months of treatment with rituximab or a rituximab-containing regimen.

The following serious adverse reactions have been associated with TREANDA in clinical trials: myelosuppression, infections, infusion reactions and anaphylaxis, tumor lysis syndrome, skin reactions, and other malignancies.

TREANDA has a unique chemical structure that is synthesized to combine an alkylating group and a purine-like benzimidazole component. Though the exact mechanism of action of TREANDA remains unknown, TREANDA may act in two distinct ways to kill cancer cells. Preclinical studies suggest that TREANDA may lead to cell death by a process known as apoptosis (programmed cell death) as well as by an alternate cell death pathway which disrupts normal cell division known as mitotic catastrophe (a non-apoptotic pathway).

Cephalon holds exclusive rights to market and develop TREANDA in the United States. TREANDA is licensed from Astellas Deutschland GmbH. Bendamustine HCl, the active ingredient in TREANDA, is marketed in Germany by Astellas’ licensee, Mundipharma International Corporation Limited. In Germany, bendamustine is indicated as a single-agent or in combination with other anti-cancer agents for indolent NHL, multiple myeloma, and CLL. SymBio Pharmaceuticals Ltd holds exclusive rights to develop and market bendamustine HCl in Japan and select Asia Pacific Rim countries.

About Cephalon, Inc.

Founded in 1987, Cephalon, Inc. is an international biopharmaceutical company dedicated to the discovery, development and commercialization of many unique products in four core therapeutic areas: central nervous system, inflammatory diseases, pain and oncology. A member of the Fortune 1000 and the S&P 500 Index, Cephalon currently employs approximately 3,000 people in the United States and Europe. U.S. sites include the company’s headquarters in Frazer, Pennsylvania, and offices, laboratories or manufacturing facilities in West Chester, Pennsylvania, Salt Lake City, Utah, and suburban Minneapolis, Minnesota.

Cephalon has a growing presence in Europe, the Middle East and Africa. The Cephalon European headquarters and pre-clinical development center are located in Maisons-Alfort, France, just outside of Paris. Key business units are located in England, Ireland, France, Germany, Italy, Spain, the Netherlands for the Benelux countries, and Poland for Eastern and Central European countries. Cephalon Europe markets more than 30 products in four areas: central nervous system, pain, primary care and oncology.

The company’s proprietary products in the United States include: NUVIGIL (armodafinil) Tablets [C-IV], TREANDA, AMRIX (cyclobenzaprine hydrochloride extended-release capsules), FENTORA (fentanyl buccal tablet) [C-II], TRISENOX, GABITRIL (tiagabine hydrochloride), PROVIGIL (modafinil) Tablets [C-IV] and ACTIQ (oral transmucosal fentanyl citrate) [C-II]. The company also markets numerous products internationally.

 

Questioning a $30,000-a-Month Cancer Drug


By ANDREW POLLACK

A newly approved chemotherapy drug will cost about $30,000 a month, a sign that the prices of cancer medicines are continuing to rise despite growing concern about health care costs.

The price of the new drug, called Folotyn, is at least triple that of other drugs that critics have said are too expensive for the benefits they offer to patients. The colon cancer drug Erbitux, for instance, costs $10,000 a month and the drug Avastin about $8,800 when used to treat lung cancer. The price of Folotyn “seems way higher than I heard of before,” Robert L. Erwin, president of the Marti Nelson Cancer Foundation, a patient advocacy group. “I can’t imagine there not being a backlash against the pricing.”

Drug makers in general have been raising prices sharply in advance of the possible passage of health care overhaul legislation, according to various studies. But the price of cancer drugs has been an issue for several years.

Critics, including many oncologists, say that patients and the health system cannot afford to pay huge prices for drugs that, on average, provide only a few extra months of life at best.

And Folotyn has not even been shown to prolong lives — only to shrink tumors. The drug was approved by the Food and Drug Administration in late September as a treatment for peripheral T-cell lymphoma, a rare and usually aggressive blood cancer that strikes an estimated 5,600 Americans each year. It is available for sale, but its manufacturer, Allos Therapeutics, does not plan to start actively promoting it until January.

Allos defends the price, saying it made a significant investment to develop the first approved drug for this type of cancer.

“It’s a very aggressive disease, and patients right now have no options,” said James V. Caruso, the chief commercial officer for Allos, a 17-year-old publicly traded company based in Westminster, Colo., that has no other drugs on the market.

Mr. Caruso also said the price of Folotyn was not out of line with that of other drugs for rare cancers. Patients, moreover, are likely to use the drug for only a couple of months because the tumor worsens so quickly, he said. So the total cost of using Folotyn will be less than for many other drugs with lower monthly prices.

“We believe we are fairly priced,” he added, “and we’re benchmarked” against other drugs. In a conference call with analysts last month, Mr. Caruso said Allos had “not had pushback of any type at this point” from insurers.

Some drugs for rare cancers are close to Foltyn’s price. Genzyme’s Clolar for pediatric leukemia costs about $34,000 a week, though the company says that only two weeks of treatment are typically needed. Genzyme’s drug Campath, for chronic lymphocytic leukemia, costs about $5,000 a week for several weeks.

GlaxoSmithKline is charging up to $98,000 for a six-month treatment course of Arzerra, a drug approved in late October for chronic lymphocytic leukemia, which strikes about 15,000 Americans a year. About $60,000 of the cost would be incurred in the first eight weeks, when the drug is given more frequently.

Gloucester Pharmaceuticals, which won approval in November for a drug to treat cutaneous T-cell lymphoma, another rare cancer, declined to discuss what it would charge when that treatment, called Istodax, goes on sale in January.

Despite such comparisons, Dr. Lee N. Newcomer, senior vice president for oncology at the big insurer UnitedHealthcare, called the price of Folotyn “unconscionable.” He said that Folotyn alone would cost as much as UnitedHealthcare now typically spends in total to treat a lymphoma patient from diagnosis until death. That median expenditure now, he said, is $87,000 for a little over a year of treatments.

But Dr. Newcomer said insurers would be obligated to pay for Folotyn because there were no alternatives.

Folotyn has not yet shown an effect on longevity. In the clinical trial that led to approval of the drug, 27 percent of the 109 patients experienced a reduction in tumor size. The reductions lasted a median of 9.4 months.

But considering all the patients in the trial, only 12 percent had a reduction in tumor size that lasted for more than 14 weeks. The trial did not compare Folotyn to another drug or a placebo.

“This drug is not a home run,” Dr. Brad S. Kahl, a lymphoma specialist at the University of Wisconsin, said during a meeting of an advisory committee to the F.D.A. on Sept. 2. “It’s not even a double. It’s a single.”

Saying that even a single was helpful, Dr. Kahl was part of a majority on the panel that recommended approval of the drug, 10 to 4.

But after recently learning what Allos planned to charge for Folotyn, Dr. Kahl said he was “disappointed” by the “excessive” price.

“It dampens my enthusiasm for using that drug,” he said. “It creates these huge ethical quandaries about trying a drug that has a modest benefit for the average patient at enormous expense.”

Folotyn is given by a rapid intravenous procedure once a week for six weeks out of every seven. Even to try the drug for the first seven-week cycle to see if it works would cost over $50,000. In the clinical trial, the median duration of use was 70 days, which would cost roughly $70,000 to $80,000. But some patients used the drug for many months.

In a note to clients in October, Joshua Schimmer, an analyst at Leerink Swann, estimated that a typical treatment would last 3.5 months and cost $126,000, or about $36,000 a month.

For investors, a high price is usually a good thing. Mr. Schimmer’s note was entitled “Folotyn Prices High, Reiterate Outperform.” He estimated annual sales of the drug in the United States reaching about $300 million by 2014.

Patient advocacy groups say that while they wish prices were lower, high prices might be needed to encourage companies to develop new drugs.

“It’s a two-edged sword that we have to live with and deal with,” said Louis J. DeGennaro, chief scientific officer of the Leukemia and Lymphoma Society, which has received donations from Allos and other companies. “A peripheral T-cell lymphoma patient,” he said, “at first blush will see this therapy as a very good thing.”

Allos, which is still unprofitable, has lost $350 million since its founding in 1992 and failed to win approval of a previous drug.

“Every dime that goes into the company supports Folotyn,” Mr. Caruso said.

At the time Folotyn was approved in September, stock in Allos briefly peaked above $8.50 but has slipped since then, closing up 16 cents at $6.62, or an increase of nearly 2.5 percent, on Friday.

After the approval, Allos raised $93 million in a secondary stock offering. In the prospectus for that offering, the company said that one of the risks for investors was “the relative price of Folotyn as compared to alternate treatment options.” It said there was a risk it might have to lower the price or offer discounts to successfully market Folotyn.

Like many other companies with high-priced drugs, Allos has established a program to help patients arrange insurance reimbursement. It says it will give the drug free to uninsured patients who cannot pay for it any other way.

And because a patient’s out-of-pocket co-payments alone — Medicare’s is 20 percent — could be thousands of dollars a month for Folotyn, Allos is financing a co-payment assistance program run by the National Organization for Rare Disorders, a patient advocacy group.

While this helps patients, it also helps the company sell more of its drug. If the 20 percent Medicare co-payment is made, then Medicare will pay the other 80 percent of the drug’s price — or about $24,000 a month.

Celgene to Acquire Gloucester Pharmaceuticals for $650 M


Gloucester PharmaceuticalsCelgene Corporation (NASDAQ:CELG) and Gloucester Pharmaceuticals Inc., a privately held pharmaceutical company, announced a definitive merger agreement under which Celgene Corporation will acquire Gloucester Pharmaceuticals. Celgene says the acquisition will continue to advance its leadership position in the development of disease-altering therapies through innovative approaches for patients with rare and debilitating blood cancers. Gloucester Pharmaceuticals develops new therapies that address the unmet medical needs in the treatment of cancer, including cutaneous T-cell lymphoma (CTCL), peripheral T-cell lymphoma (PTCL) and other hematological malignancies.

ISTODAX® (romidepsin) was approved in November 2009, by the U.S. Food and Drug Administration (FDA) for the treatment of CTCL in patients who have received at least one prior systemic therapy.  Additionally, ISTODAX has received both orphan drug designation for the treatment of non-Hodgkin’s T-cell lymphomas, which includes CTCL and PTCL, and Fast Track status in PTCL from the Food and Drug Administration (FDA). The European Agency for the Evaluation of Medicinal Products (EMEA) has granted orphan status designation for ISTODAX for the treatment of both CTCL and PTCL. Accrual of the ISTODAX registration SPA Trial for peripheral T-cell lymphoma (PTCL) is expected to be completed early next year.Celgene

“We are thrilled with this transaction because Celgene’s global leadership in the development and commercialization of innovative treatments for hematologic diseases makes the

m ideally suited to bring the clinical benefits of ISTODAX to patients with CTCL,” said Alan Colowick, M.D., Chief Executive Officer of Gloucester Pharmaceuticals.

CTCL is a type of non-Hodgkin’s lymphoma (NHL) caused by a mutation of T-cells; most types of NHL are of T-cell origin. The malignant T-cells involve the skin, causing plaques, patches, erythroderma and/or tumors and can involve other organs, including the blood, lymph nodes and viscera. According to the Cutaneous Lymphoma Foundation, this rare orphan disease has a greater frequency among men than women; the disease is more common after the age of 50.

“This acquisition reflects our ongoing commitment to improving the lives of patients worldwide through innovative medicines discovered and developed both in-house and through external opportunities,” said Sol J. Barer, Ph.D., Chairman and Chief Executive Officer of Celgene Corporation. “We also would like to recognize the dedication, effort and leadership that Alan and his team have demonstrated in the process of developing and delivering ISTODAX® to patients living with CTCL.”

About Terms of the Agreement
The transaction has been approved by the Board of Directors of both companies and is subject to customary closing conditions, including the expiration or termination of the applicable waiting period under the Hart-Scott-Rodino Antitrust Improvements Act of 1976. Under the terms of the merger agreement, Celgene will acquire Gloucester Pharmaceuticals for $340 million in cash plus $300 million in future U.S. and international regulatory milestone payments. The acquisition of Gloucester will be accounted for as a purchase transaction that Celgene expects to be completed in the first quarter of 2010 and to be neutral to non-GAAP diluted earnings for 2010 and accretive in 2011. J.P. Morgan Securities Inc. acted as the exclusive financial advisor to Gloucester Pharmaceuticals.

About ISTODAX
ISTODAX® (romidepsin) is a member of a new class of cancer drugs known as histone deacetylase (HDAC) inhibitors. HDACs catalyze the removal of acetyl groups from acetylated lysine residues in histones, resulting in the modulation of gene expression. HDACs also deacetylate non-histone proteins, such as transcription factors. HDAC inhibitors can be divided into four main classes: cyclic tetrapeptides (I), short-chain fatty acids (II), hydroxamic acids (III), and benzamides (IV). The cyclic peptide structure of ISTODAX is novel among the cyclic tetrapeptides. In vitro, ISTODAX causes the accumulation of acetylated histones, and induces cell cycle arrest and apoptosis of some cancer cell lines. For full prescribing information, visit www.ISTODAX.com.

About Gloucester Pharmaceuticals
Founded in 2003, Gloucester Pharmaceuticals, Inc. is a privately held biopharmaceutical company that acquires clinical-stage oncology drug candidates with the goal of advancing them through regulatory approval and commercialization. Gloucester’s first drug, ISTODAX® (romidepsin), a novel histone deacetylase (HDAC) inhibitor, was approved in November 2009, by the U.S. Food and Drug Administration for the treatment of cutaneous T-cell lymphoma (CTCL) in patients who have received at least one prior systemic therapy. The Company is also conducting a registration trial in peripheral T-cell lymphoma (PTCL) with an anticipated supplemental NDA filing in 2010 for this indication. Additional studies in both hematologic and solid tumors are currently ongoing.  ISTODAX is approved for the treatment of CTCL in the U.S. and is not approved for the treatment of PTCL or other indications. Gloucester’s investors include Prospect Venture Partners, Rho Ventures, ProQuest Investments, Apple Tree Partners and Novo A/S.

About Celgene
Celgene Corporation, headquartered in Summit, New Jersey, is an integrated global biopharmaceutical company engaged primarily in the discovery, development and commercialization of innovative therapies for the treatment of cancer and inflammatory diseases through gene and protein regulation.

Quark Pharmaceuticals progresses on eye disease study


Quark founder and CEO Dr. Daniel Zurr said, “Over the next 15 months, at least one of our programs should enter a Phase III trial.”

Gali Wienreb

RNA interference (RNAi)-based drug development company Quark Pharmaceuticals Ltd. has reported that it has completed recruitment for its Phase II clinical trial of RTP-801i, its treatment for diabetes macular edema. Quark is developing the drug with Pfizer Inc. (NYSE: PFE; LSE: PFZ), which has the marketing license to the drug.

Pfizer is conducting its own Phase II clinical trial of RTP-801i for age-related macular degeneration (AMD). It purchased the rights for the drug for this purpose from Quark as part of the same licensing agreement.

Quark has also completed patient recruitment for two studies that it is conducting independently. One study is a Phase I clinical trial of its drug for the prevention of acute kidney injury following heart surgery. The second study is a Phase I/II trial of drug candidate QPI-1002 for the prevention of damage to kidney transplants,when the functioning of the new organ is delayed.

Quark hopes that, during the first quarter of 2010, it will begin recruiting patients for an independent study of drug candidate QPI-1007 for protecting nerve cells in the eye from degenerative diseases, such as glaucoma.

Quark founder and CEO Dr. Daniel Zurr said, “Over the next 15 months, at least one of our programs should enter a Phase III trial. We are currently undertaking four trials under US Food and Drug Administration (FDA) Investigational New Drug (IND) guidelines, and a fifth trial is slated to begin shortly.”

Quark’s drugs are based on new mechanisms for drug discovery. The company has developed a technique for investigating the effects of various genes on a range of illnesses by selectively silencing the genes. Both AKLi-5 and RTP-801i are silencing RNA (siRNA) drugs that temporarily inhibit the expression of human p53. The company currently only has Phase I trial results for RTP-801i for AMD, and the treatment was found to be safe.

In 2006, Quark raised tens of millions of dollars in a round led by Japanese funds. It signed the strategic agreement with Pfizer in the same year, under which the company transferred to Pfizer several molecules under development. Pfizer invested tens of millions of dollars in Quark at the time of the agreement, and Quark’s income from the agreement could reach hundreds of millions of dollars in the long term if the drugs reach market.

In early 2007, Quark planned to hold an IPO on Nasdaq on the basis of the Pfizer agreement. The company planned to raise $75 million at a company value of $250-300 million, but withdrew the offering when the market rejected the valuation.

The present announcement may be a feeler aimed at testing a new Nasdaq IPO, now that Quark has several products in the pipeline.

Published by Globes [online], Israel business news – www.globes-online.com – on December 2, 2009

© Copyright of Globes Publisher Itonut (1983) Ltd. 2009

Trellis Bioscience, Inc. Grants MedImmune License for Its Anti-RSV Antibodies in Deal Worth Potentially $338 Million


TrellisTrellis Bioscience, Inc. announced today the granting of a worldwide exclusive license to MedImmune, LLC, the global biologics unit of AstraZeneca, to develop and commercialize Trellis’ antibodies directed against the respiratory syncytial virus (RSV).

Under the terms of the agreement, MedImmune will pay Trellis an upfront cash payment upon signing, as well as additional payments for potential development, regulatory, and commercial milestones. The total payments have the potential to reach $338 million should a product resulting from this licensing agreement reach the market. MedImmune will be responsible for all preclinical and clinical development and commercialization of Trellis’s RSV antibodies worldwide. MedImmune will also pay Trellis royalty payments based on worldwide product sales.

The RSV antibodies were discovered using Trellis’ proprietary CellSpotTM discovery platform, which allows high throughput screening of human B-cells in a multiplexed format, thus enabling rapid identification and isolation of extremely rare human antibodies produced from the B-cells of RSV infected patients.

“We are excited to partner our unique anti-RSV antibodies with MedImmune,” commented James Posada, chief business officer of Trellis. “Given the company’s deep expertise in the field of RSV, we believe MedImmune is the best possible partner for this molecule.”

“The discovery of these antibodies further validates the Trellis CellSpot platform and its ability to screen millions of human B cells to identify very rare human antibodies generated by the human body to fight infection, in this case RSV,” added Stote Ellsworth president and chief technology officer of Trellis.

About CellSpot

Trellis’s patented CellSpot platform is a high throughput, cell analysis technology that enables simultaneous measurement of up to 10 antibody characteristics from single antibody secreting cells, including probes for specificity and affinity. Raising the quality threshold in the primary screen in this manner reduces the hit rate to a level that cannot be reliably accessed without the high throughput enabled by CellSpot’s extreme assay miniaturization. With CellSpot, millions of individual antibody producing cells can be characterized in detail in a few days, generating orders of magnitude more information than conventional methods. CellSpot can thereby examine the entire human repertoire in order to identify cells producing superior antibodies. As fully human antibodies, pre-screened for lack of cross-reactivity to normal human proteins, such antibodies offer the prospect of maximal safety.

About Trellis Bioscience

Trellis Bioscience, Inc. is a private, venture-funded, antibody company focused on the discovery and development of unique therapeutic antibodies from human B cells. To exploit this highly favorable but technically difficult antibody source, Trellis developed its patented CellSpot antibody discovery platform, which enables the rapid identification of rare, superior antibodies directly from human blood. The Company is initially focused on infectious disease targets, with the lead program providing therapeutic antibodies directed against Respiratory Syncytial Virus.

Pfizer And Protalix Enter Into Agreement To Develop And Commercialize Gaucher’s Disease Treatment


Pfizer Deal Signals a Move Into Treating Rare Diseases

ProtalixBy ANDREW POLLACK

The world’s largest drug company is thinking small.

Pfizer said Tuesday that it had licensed the worldwide rights to a treatment for Gaucher disease, a rare genetic disorder, from Protalix Biotherapeutics, an Israeli biotechnology company.

The deal signals the start of an effort by Pfizer to enter the business of selling ultra-expensive drugs for ultra-rare diseases, a market that big pharmaceutical companies once largely ignored.

And the move will put the company into direct competition with Genzyme, the biotechnology company that already sells a drug called Cerezyme to trePfizerat Gaucher disease.

Genzyme has been struggling to recover from a severe shortage of Cerezyme brought about by manufacturing problems.

Pfizer will pay Protalix $60 million initially and up to $55 million later. The companies will split expenses to market the drug and the revenue from its sales on a 60-40 basis, with Pfizer having the larger share.

Protalix is close to filing its application for federal approval of the drug. The product, called taliglucerase alfa, could reach the market next year.

Although analysts viewed the deal as a validation of Protalix’s drug and its novel manufacturing process, shares of Protalix fell nearly 14 percent, to $8.51, apparently because investors were disappointed that Pfizer did not acquire the company. Pfizer’s shares rose nearly 4 percent, to $18.85.

Protalix makes proteins that serve as drugs in genetically engineered carrot cells that grow inside plastic bags. That is far less costly, it says, than the process used by most biotechnology companies, including Genzyme, which is to use genetically engineered hamster ovary cells growing in stainless steel tanks.

That will probably mean that Protalix’s taliglucerase will be cheaper than Cerezyme, though executives at Pfizer and Protalix declined to discuss the price on Tuesday.

Big pharmaceutical companies once tended to disregard rare diseases, preferring to develop blockbusters for common ailments like diabetes and high cholesterol. But with sales growth slowing and older blockbusters losing patent protection, the companies have become more willing, even eager, to sell specialized drugs.

“This is the first step in the pursuit of a formal strategy around orphan drugs and rare diseases,” David Simmons, president of Pfizer’s established products business unit, said in an interview.

While there might be few patients with each disease, he said, “collectively, it’s a very large patient population with a great unmet medical need.”

Besides, Genzyme has proved that even a drug for a rare disease can generate big sales if the price of the drug is high enough. Only about 5,700 people in the world are being treated with Cerezyme. But since the drug costs about $200,000 a patient each year, sales exceeded $1 billion last year.

Pfizer is not alone in pursuing treatments for rare diseases. In October, GlaxoSmithKline announced a deal with Prosensa, a Dutch company, to develop drugs for Duchenne muscular dystrophy. And in June, Novartis won approval from the Food and Drug Administration to sell its drug Ilaris as a treatment for cryopyrin-associated periodic syndrome. Only about 300 Americans suffer from that syndrome, an inflammatory condition caused by a gene mutation.

Philip Nadeau, an analyst at Cowen & Company, called the entrance of Pfizer as a competitor a “modest negative” for Genzyme. However, Mr. Nadeau said, “even Pfizer’s marketing prowess is unlikely to relieve” safety concerns some doctors have about the Protalix drug. The main concern is that because it is produced in plant cells, taliglucerase may spur immune reactions in some patients.

Genzyme’s stock rose a bit less than 1 percent, to $51.11. The company announced Monday that it had resumed shipping some newly manufactured Cerezyme. Manufacturing had been shut down in June after a virus contaminated the company’s factory in Boston.

The shortfall left Genzyme vulnerable to Protalix and also to Shire, a British drug company that is also developing a drug for Gaucher disease. Because of the shortage, the Food and Drug Administration has been allowing some patients to use the Shire and Protalix drugs even though they have not been approved.

Gaucher disease is an enzyme deficiency that can cause an enlarged liver and spleen, anemia, frequent bleeding and bone weakness. All three drugs consist of the enzyme that people with Gaucher disease are missing.

Alberta researcher makes stem cell breakthrough that could help premature babies


EDMONTON — An international team headed by a University of Alberta researcher has used stem cells to heal and protect the lungs of newborn rats – research that could help premature babies with chronic lung disease.

Dr. Bernard Thebaud’s team injected stem cells from bone marrow into the rats’ airways. Two weeks later the rodents were running twice as far on treadmills and had better survival rates.

The stems cells acted like tiny damage control factories, pumping out a healing liquid that scientists are working to understand.

“That healing liquid seems to boost the power of healthy lung cells and helps them to repair the lungs,” said Thebaud, who is also a specialist at Edmonton’s Stollery Children’s Hospital neonatal intensive care unit.

“The human implication is that we envision a stem cell-based treatment for these babies that suffer from chronic lung disease.”

Babies who are born extremely prematurely can’t breathe on their own and need help for their lungs to develop properly. About half of babies born before 28 weeks get chronic lung disease, a condition that can affect lung capacity as they grow up.

Thebaud and his team’s findings are to be published Dec. 1 in the American Journal of Respiratory and Critical Care Medicine and are already attracting international attention. The team included researchers from Montreal, France and the U.S.

“I want to congratulate Dr. Thebaud and his team,” said Dr. Roberta Ballard, a professor of pediatrics at the University of California. “In a few short years I anticipate we will be able to take these findings and begin clinical trials with premature babies.”

Stem cells can develop into different cell types in the body. They can act as an internal repair system, dividing to replenish other cells.

The team, which is partly funded by the Alberta Heritage Foundation for Medical Research, is now looking at the longer-term safety of using stem cells for lung therapy. There is some concern that stem cells could transform into tumours because they have the potential to become any type of cell.

Researchers want to see if the rats show any signs of cancer after they are treated.

The team is also studying the healing liquid produced by the stem cells.

Thebaud said it may be possible to use that liquid on its own to repair and heal the lungs, making the injection of the cells unnecessary.

“Now the million-dollar question is ‘What are (the cells) producing and can we harness that? can we use it as medication?”‘ he said. “We could take that fear out of the equation.”

During the research project Thebaud said he spent many hours peering through his microscope at rat tissue and watching the rodents running on treadmills.

But the image in his mind was always of the premature babies he has treated with damaged lungs that are kept alive on ventilators.

“You see those rats running on the treadmill and you think of a kid who could be able to run with his peers, play soccer or hockey,” he said. “That’s what matters.”

Kangaroos give a lesson in skin cancer prevention


Understanding how kangaroos repair their DNA could be the key to preventing skin cancer in the future, according to new research by Dr Linda Feketeová and Dr Uta Wille from the ARC Centre of Excellence for Free Radical Chemistry and Biotechnology at The University of Melbourne.

Together with scientists from The University of Innsbruck, Austria, Dr Feketeová and Dr Wille are working toward reducing the number of skin cancer-related cases by investigating the chemistry behind potential skin cancer therapies.

The teams are investigating a DNA repair enzyme found in kangaroos and many other organisms, but not humans. This enzyme is very effective in repairing a particular type of DNA damage linked to many skin cancers.

“As summer approaches, excessive exposure to the sun’s harmful UV light will see more than 400,000 Australians diagnosed with skin cancer,”  says Dr Feketeová.

“Other research teams have proposed a ‘dream cream’ containing the DNA repair enzyme which you could slap on your skin after a day in the sun. We are now examining whether this would be feasible by looking at the chemistry behind the DNA repair system.”

Using highly sophisticated technology, the groups are simulating the skin’s UV exposure in the laboratory, and then analysing the DNA repair process in a specialised mass spectrometer instrument.

“We were quite surprised that the DNA’s repair process also resulted in a number of chemical by-products, which have never been seen before,” says Dr Wille”Our plan is to study these products to understand if the DNA repair enzyme could be incorporated into a safe and effective method for skin cancer prevention.”

“But there is still much to investigate before this ‘dream cream’ will be available at the pharmacy, so don’t throw out your sunscreen just yet!” adds Dr Feketeová.

This work will be published as a “hot paper” in the upcoming edition of Chemical Communications.


Harvard team heralds cancer vaccine breakthrough


New approach reprograms the mammalian immune system to attack tumors body-wide
CAMBRIDGE, Mass. – November 25, 2009 – A cancer vaccine carried into the body on a carefully engineered,

David J. Mooney

David J. Mooney

fingernail-sized implant is the first to successfully eliminate tumors in mammals, scientists report this week in the journal Science Translational Medicine.

The new approach, pioneered by bioengineers and immunologists at Harvard University, uses plastic disks impregnated with tumor-specific antigens and implanted under the skin to reprogram the mammalian immune system to attack tumors. The new paper describes the use of such implants to eradicate melanoma tumors in mice.

“This work shows the power of applying engineering approaches to immunology,” says David J. Mooney, the Robert P. Pinkas Family Professor of Bioengineering in Harvard’s School of Engineering and Applied Sciences and Wyss Institute for Biologically Inspired Engineering. “By marrying engineering and immunology through this collaboration with Glenn Dranoff at the Dana-Farber Cancer Institute, we’ve taken a major step toward the design of effective cancer vaccines.”

Most cancer cells easily skirt the immune system, which operates by recognizing and attacking invaders from outside the body. The approach developed by Mooney’s group redirects the immune system to target tumors, and appears both more effective and less cumbersome than other cancer vaccines currently in clinical trials.

Conventional cancer vaccinations remove immune cells from the body, reprogram them to attack malignant tissues, and return them to the body. However, more than 90 percent of reinjected cells have died before having any effect in experiments.

The slender implants developed by Mooney’s group are 8.5 millimeters in diameter and made of an FDA-approved biodegradable polymer. Ninety percent air, the disks are highly permeable to immune cells and release cytokines, powerful recruiters of immune-system messengers called dendritic cells.

These cells enter an implant’s pores, where they are exposed to antigens specific to the type of tumor being targeted. The dendritic cells then report to nearby lymph nodes, where they direct the immune system’s T cells to hunt down and kill tumor cells.

“Inserted anywhere under the skin — much like the implantable contraceptives that can be placed in a woman’s arm — the implants activate an immune response that destroys tumor cells,” Mooney says.

The technique may have powerful advantages over surgery and chemotherapy, and may also be useful in combination with existing therapies. It only targets tumor cells, avoiding collateral damage elsewhere in the body. And, much as an immune response to a bacterium or virus generates long-term resistance, researchers anticipate cancer vaccines will generate permanent and body-wide resistance against cancerous cells, providing durable protection against relapse.

Mooney says the new approach’s strength lies in its ability to simultaneously regulate the two arms of the human immune system: one that destroys foreign material and one that protects tissue native to the human body. The implant-based vaccine recruits several types of dendritic cells that direct destructive immune responses, creating an especially potent anti-tumor response.

“This approach is able to simultaneously upregulate the destructive immune response to the tumor while downregulating the arm of the immune system that leads to tolerance,” Mooney says. “In cancer, this latter arm is typically a limiting feature of immunotherapies, since it can extinguish vaccine activity and afford tumors a degree of protection.”

###
Mooney’s co-authors are Omar A. Ali of Harvard’s School of Engineering and Applied Sciences and Wyss Institute for Biologically Inspired Engineering and InCytu, Inc.; Dwaine Emerich of InCytu, Inc.; and Glenn Dranoff of Dana-Farber Cancer Institute, Brigham and Women’s Hospital, and Harvard Medical School. Their work was supported by the National Institutes of Health, Harvard University, and InCytu, Inc.

Document Actions

Biotech bills give drugmakers too many years of exclusivity


THE BIOTECH INDUSTRY is vital to the Massachusetts economy and the complex drugs made by companies here deserve robust protection as intellectual property. But giving exclusive markets to those companies for too long means that the drugs are priced beyond the reach of some patients for years – and it only adds to the upward pressure on health care costs.

But giving exclusive markets to those companies for too long means that the drugs are priced beyond the reach of some patients for years – and it only adds to the upward pressure on health care costs.

That’s too long, more than double the five years of protection from competition guaranteed for conventional drugs. It’s quite likely that extensive lobbying accounts for some of the disparity; The New York Times recently reported that lobbyists for the biotech firm Genentech ghostwrote parts of official statements made by 42 members of Congress on the parts of the health care reform bill related to generic biotech drugs.

The 12-year protection is also excessive because competition from generics is not likely to erode the ability of the original biotech manufacturers to continue reaping profits. There are onerous technical barriers to making so-called biogenerics, unlike generic versions of conventional medications, so companies that invent original drugs are likely to retain market share despite the new competition. In Europe, where a path for approving generic versions of biologics already exists, the original drugs’ prices have dropped only by about 25 to 30 percent, according to the New England Journal of Medicine.

The downside of this, of course, is that approving generic versions is unlikely to eliminate the drugs’ annual five- and six-figure price tags anytime soon.Yet even modest savings add up. Medicare spends more than $2 billion per year on just one biologic drug, Epogen, used to treat anemia in kidney patients. The Congressional Budget Office estimates that the government could save more than $9 billion over the next decade if biogenerics come on the market after seven years. The long-term savings would be even greater.

In clearing the path for generic alternatives to expensive biologics, Congress should enact a shorter window of market exclusivity than 12 years, but more than the five years afforded to simpler, conventional drugs. A protection period that falls directly in between these extremes would strike a balance between encouraging companies to make biologic drugs and making them affordable.

In this case, what’s optimal for Massachusetts drug firms is not good for the nation or for suffering patients. A compromise is necessary. 

Novartis opens new flu vaccine plant in U.S.


By Jason Arthurs

The bioreactors are empty and running just for show for now, but Novartis opened its first U.S. flu vaccine plant on Tuesday, the first in the country to make flu vaccines out of cells instead of eggs.

Health and Human Services Secretary Kathleen Sebelius toured the plant, whose cell-based technology is designed to be cleaner, quicker and more predictable than the current way most influenza vaccines are made using eggs and will help alleviate the U.S. dependence on imported vaccines.

The bioreactors used to incubate the cells with the virus should also be able to scale up more quickly to make larger quantities of vaccine when needed — such as during pandemics.

It will be years before the facility makes any real vaccine, so it is of no use during the current pandemic of H1N1 swine flu, in which the government is struggling to vaccinate Americans in the face of slow-arriving supplies.

“Cell culture technology for influenza vaccines is not yet approved in the United States; however, part of the HHS contract support for Holly Springs includes funding for the development of a flu cell culture vaccine,” Novartis said in a statement.

“If licensed in an emergency, the facility will be ready to respond to a pandemic as early as 2011. The plant is planned to be running at full scale commercial production in 2013,” it added.

The company operates a cell culture flu vaccine plant in Marburg, Germany, which makes vaccine for the European Union, Iceland and Norway.

The U.S. Centers for Disease Control and Prevention estimates 22 million Americans have been infected with H1N1 flu and it wants to vaccinate at least 160 million people. But just over 50 million H1N1 vaccines have been distributed.

The Health and Human Services Department invested $487 million to help Novartis build the plant in the hopes of making the U.S. flu vaccine supply more reliable.

BILLION DOLLAR INVESTMENT

“The total investment in the facility is nearly $1 billion, through a partnership between Novartis and HHS to support the design, construction, validation and licensing of the manufacturing facility in Holly Springs,” the company said.

When it gets up and going, Novartis says the Holly Springs facility will be able to make 50 million doses of seasonal flu vaccine a year and up to 150 million doses of pandemic vaccine within six months of a pandemic being declared.

“As Congress heard in H1N1 preparedness hearings, the United States needs vaccine production that is more reliable and domestically produced,” David Price, the U.S. House of Representatives member who represents Holly Springs as part of his district, told a ceremony at the plant.

“Since the vast majority of influenza vaccinations are made abroad, Novartis … will put the United States in a better position to meet future influenza threats,” he said.

Wary of uncertain flu vaccine supplies, HHS has contracted with five different companies to make influenza immunizations for the U.S. market — Novartis, Sanofi Aventis, CSL, AstraZeneca unit MedImmune and GlaxoSmithKline.

In 2004, British authorities closed a contaminated plant making vaccine for the U.S. market, cutting in half the U.S. seasonal flu vaccine supply.

Sanofi has a flu vaccine plant in Pennsylvania, but other flu vaccines for the U.S. market are made in other countries.

Many experts have cautioned that in the event of a very serious pandemic, countries would be likely to seize any vaccines made within their own territories.

(Writing by Maggie Fox; Editing by David Storey)

Given unveils next-generation Colon Pillcam


Given Imaging has already obtained the EU CE Mark for the Pillcam Colon2.
Globes’ correspondent23 Nov 09 14:50

Endoscopic capsule developer Given Imaging Ltd. (Nasdaq: GIVN; TASE: GIVN) today unveiled its next-generation Pillcam Colon at the Gastro 2009 Conference in London. The Pillcam Colon2 is a development of the Pillcam Colon1, and is aimed at being more patient friendly, as well as providing better visualization of the colon.

The Pillcam Colon2 includes proprietary, innovative technologies, including intelligent functionality and superior imaging, designed to provide physicians with clear and precise views of the colon and polyps of interest.

Given Imaging has already obtained EU CE Mark certification for the Pillcam Colon2 and has begun marketing in select European countries, with continent wide availability planned by mid-2010.

The Pillcam Colon2 has two-way communications to improve the capsule’s motion and imaging. The number of images has been increased to 35 frames per second from four frames per second. Advanced optics provides a 172-degree field of view offering a near 360-degree view of the colon.

A comparative study of which PillCam Colon2 to colonoscopy at five hospitals in Israel showed a sensitivity of 89% and a specificity of 76% in detecting polyps six mm or larger, and a sensitivity of 88% and a specificity of 89% in detecting polyps ten mm or larger. The study included 98 patients who had risks or warning symptoms of colon disease.

Given Imaging president and CEO Homi Shamir said, “PillCam Colon2 incorporates the cumulative expertise gained from the first PillCam Colon as well as more than one million PillCam capsule ingestions worldwide. Despite the small size of this initial study and the relatively low prevalence of polyps, we are very encouraged by this data and look forward to working with leading gastroenterologists in Europe, the United States and other markets to initiate additional clinical trials.”

Given Imaging also has Pillcams for the small bowel and esophagus.

Given Imaging closed at $16.92 on Nasdaq on Friday, giving a market cap of $495 million, and rose over 4% in premarket trading today. The share rose 4.3% by mid-afternoon on the TASE to NIS 66.93.

Published by Globes [online], Israel business news – www.globes-online.com – on November 23, 2009

© Copyright of Globes Publisher Itonut (1983) Ltd. 2009

UK Gov’t Commits £150 Million to European VC Fund


big-ben-london-clock-towerLONDON (Reuters) – The government on Friday pledged 150 million pounds ($246 million) to a new venture capital fund, planned as Europe’s largest, as it looks to kick start British technology investment and the ailing business sector.

The government hopes to build up the fund to 1 billion pounds over ten years and has been calling on private sector investors to invest alongside it in the UK Innovation Investment Fund, science and innovation minister Lord Drayson said.

“The fund will be the largest technology venture capital fund raised in Europe and will be able to match the scale of the funds we see being raised in the U.S.,” Drayson told Reuters in a telephone interview.

“The UK has a very strong group of technology businesses which require venture capital and we are addressing that today,” he added.

The government has seen strong support from private sector investors for the innovation fund of funds, which will invest in venture capital funds targeting technology companies in the UK as well as Europe, Drayson said.

A fund of funds manager will be appointed next month, Drayson said, when the fund will also announce a first close — the point after which it can start investing the capital initially committed.

British venture capital firms and the businesses they back have long struggled to keep up with their U.S. rivals as investors in the UK have traditionally put less money into the sector, starving businesses of funding.

The UK is the second largest venture capital market in the world but only receives 4 percent of investors’ funds, compared with 30 percent in the United States, the leading market, according to data from Department for Business Innovation and Skills.

However, the government is hoping the scale of the innovation fund will allow larger sums to be invested in individual companies, supporting the growth of the technology sector, Drayson said.

The government recently backed a proposal from Chris Rowlands, a former executive at British private equity firm 3i Group (III.L), to establish a complementary fund providing financing for small and medium sized companies. ($1=.6105 Pound) (Editing by Joel Dimmock)

http://www.biojobblog.com/bigben.jpg

Distracted By Merger, Pfizer Waffles on Future Of La Jolla Incubator


By HEATHER CHAMBERS, San Diego Business Journal Staff

Two years ago, Pfizer Inc. dedicated a building on the campus of its La Jolla laboratories to fledgling life sciences companies where they could focus on research without worrying about raising money or buying expensive equipment.

One of eight buildings on its sprawling 33.5-acre La Jolla campus, The Pfizer Incubator was designed as a place where early stage ideas could grow in exchange for Pfizer’s rights to acquire any resulting products or technologies. The pharmaceutical giant committed to funding each company for roughly $2 million a year for two years.

It soon welcomed three San Diego startups — Fabrus LLC, Wintherix LLC and RGo Bioscience LLC — with promising new approaches to drug development and the potential for Pfizer to reinvigorate its product pipelines.

The first company to graduate the program this year, Fabrus, quietly walked away without a Pfizer contract.

“Pfizer has been caught up with the integration of Wyeth, and Fabrus will be spinning out as an independent entity,” Fabrus CEO Vaughn Smider wrote in an e-mail last week.

The small biotech was testing a technology for identifying antibodies that may one day lead to new drugs.

Smider did not say what led to Pfizer’s decision and calls made to Pfizer seeking more information were not returned by deadline.

Merger Drives Uncertainty

Pfizer spokeswoman Samantha Cummis said most of the details surrounding the incubator’s future are still being worked out as Pfizer merges operations with Wyeth Pharmaceuticals.

“Right now, it’s status quo,” she said.

But the pharmaceutical giant, which pledged in 2007 to invest $10 million a year over five years in the program, hasn’t made any new investments this year. In March, it put the 26,600-square-foot incubator building up for sale under a partial lease-back arrangement, causing some concern among occupants who feared Pfizer would place less emphasis on the program moving forward. The building remains for sale today, according to Cushman & Wakefield Inc. broker Steve Rosetta.

Since the incubator began, circumstances have changed dramatically for the pharmaceutical giant. Its $68 billion merger with rival drug maker Wyeth has resulted in thousands of job reductions and the closure of six of 20 research facilities worldwide.

Its La Jolla laboratories, which serve as a global hub for cancer research and employ roughly 1,000 people, were spared from the cuts. But the future of its incubator remains uncertain.

J&J wants deals with rivals to share risk


By Andrew Jack

Johnson & Johnson, the US healthcare group, will in future take more long-term minority stakes and forge alliances with rival pharmaceuticals companies in an effort to share the rising costs and risks of drug development.

William Weldon, chief executive, told the Financial Times: “The cost of developing compounds has become so high and become so risky that we are looking to share the risks and opportunities and find more and more partnerships.”

His remarks reflect a trend even by large, cash-generative pharmaceuticals companies to find new ways to share the potential costs as well as the profits in proving the safety and efficacy of new drugs to regulators and winning agreement by healthcare systems to reimburse them.

Mr Weldon stressed that he had no deals under consideration, but that US healthcare reform had added even more uncertainty to the environment for drug development. “You’ll see more and more sharing of risks because the upside can be spectacular.”

The comments came in an interview after J&J recently approved alliances involving the purchase of 18 per cent of the equity of Elan, the Ireland-domiciled biotech company, for Alzheimer’s and multiple sclerosis drugs, and a similar investment in Crucell, the Dutch vaccines business.

In a different tack, J&J also this summer signed an alliance with Gilead, the US biotech group, by joint trials to develop a once-daily HIV therapy combining J&J’s experimental medicine TMC278, with Gilead’s Truvada, which combines its drugs Viread and Emtriva.

J&J has long managed at arm’s length many subsidiaries in its three divisions covering consumer healthcare, medical devices and drugs. It allows them to retain considerable autonomy. But it has usually chosen fully to acquire these companies and centralise back-office operations.

A growing number of large pharmaceuticals companies that traditionally took full control of drug development are forging similar partnerships to share risks, including GlaxoSmithKline and Pfizer, which are combining their experimental and existing HIV medicines into a joint venture.

Bristol-Myers Squibb has agreed joint drug development projects with AstraZeneca for cancer and with Gilead for HIV.

As a result of its Elan deal, J&J has also become linked to Elan’s existing partners, Biogen Idec and Wyeth, now part of Pfizer, with which it is developing Alzheimer’s drugs. “We are very happy to partner with Wyeth,” Mr Weldon said.

In both Elan and Crucell deals, the company has agreed to a standstill in its equity holdings for the coming years.

Novartis strikes licensing deal with Incyte


Incyte* Gains access to 2 therapies for blood disorders, cancers

* Novartis to pay Incyte $150 million upfront

* Also pays $60 mln milestone at start of Phase III trial

* Incyte shares rise 5.3 pct; Novartis up 0.6 pct

ZURICH, Nov 25 (Reuters) – Swiss drugmaker Novartis  has struck a licensing deal with Incyte Corp, paying $150 million up front for access to therapies to treat patients with life-threatening blood disorders and cancers.

Incyte shares rose as much as 11.9 percent to their highest level in 14 months.

novartis3-07

The move, which boosts Novartis’ position in oncology, gives it rights to Incyte’s experimental Janus kinase, or JAK, inhibitor outside the United States and to future development of an early-stage cMET inhibitor globally, Novartis said.

Incyte’s JAK inhibitor, known as INCB18424, is in Phase III clinical trials for the treatment of myelofibrosis, a life-threatening condition with no effective medical treatment.

Novartis will pay $150 million upfront to Incyte and $60 million tied to a European study of INCB18424 that began in July. Incyte is also eligible for milestone payments and royalties on future sales.

JPMorgan analyst Cory Kasimov said the deal terms for Incyte “exceed expectations, and importantly, are all the more impressive when considering that Incyte was able to retain 100 percent of U.S. rights.

“Management has clearly delivered a high quality deal with an ideal partner that has formidable experience building a market in the hematology-oncology field,” Kasimov said in a research note.

Incyte shares were up 41 cents, or 5.3 percent, at $8.13 in morning Nasdaq trading, where they rose as high as $8.64. Novartis shares rose 0.6 percent.

Kepler analyst Tero Weckroth said the deal did not seem to be overly expensive, especially as the JAK inhibitor was in late-stage trials: “The deal is neutral to slightly positive to sentiment.”

Myelofibrosis is characterized by varying degrees of bone marrow failure, enlarged spleen and debilitating symptoms, Novartis said.

“INCB18424 has the potential of becoming a first-in-class therapeutic agent for the treatment of this and other hematologic diseases,” the company said.

NicOx Completes $44.92M Fundraising as FDA Accepts NDA for Osteoarthritis Drug


NicOx completed a €30 million (about $44.92 million) private placement with institutional investors. The company separately reported that the FDA accepted its NDA submission for lead osteoarthritis drug, naproxcinod.Nicox logo 2012

The fundraising included a €20 million (about $29.95 million) cornerstone investment by Fonds Stratégique d’Investissement (FSI), which as a result now owns 5.1% of NicOx. Proceeds from the financing round will be used to support NicOx’ drive to become a fully integrated specialty pharmaceuticals company.

NicOx is focused on developing a pipeline of nitric oxide-donating drugs. Naproxcinod is a cyclooxygenase-inhibiting nitric oxide-donating (CINOD) anti-inflammatory agent being developed for relieving the signs and symptoms of osteoarthritis. In addition to its recent NDA submission, NicOx says that it also aims to file for regulatory approval in Europe by the end of this year.

Just last week the company reported positive results from a Phase Ib study with NCX 6560, a nitric oxide-donating HMG-CoA reductase inhibitor in development for cardiovascular indications. The trial, evaluating NCX 6560 versus placebo and Lipitor®, met its primary and secondary endpoints and demonstrated a strong cholesterol-lowering effect in patients with high baseline LDL cholesterol levels.

“The role of NO in preventing pathological processes in the vasculature suggests NCX 6560 could have the potential to reduce the occurrence of serious cardiovascular adverse events such as stroke and heart attack in coronary heart disease patients,” notes Pascal Pfister, CSO and head of R&D at NicOx. “In light of these results, we are keen to see NCX 6560 advanced into Phase II.”

 

GEN_logo

Israeli Gov't to invest $80m in biotech fund


The Finance Ministry and Chief Scientist yesterday published the tender for the biotech fund.
Gali Weinreb

The Ministry of Finance and Office of the Chief Scientist yesterday published the tender for the government biotechnology fund, announced six months ago. According to the tender documents, the government will invest $80 million in the venture.

Sources involved in the tender said that a study by the Ministry of Finance and Office of the Chief Scientist found that the government investment could be leveraged four-fold. Previously, the fund’s organizers mentioned two to three-fold leverage, and capital markets were skeptical about the target.

The tender is slightly different from the call for proposals published two months ago, as well as from the original format defined for the biotech fund. The main difference is that the fund’s manager will have to invest $75-100 million in pharmaceutical and biotechnology companies. The fund manager will be able to investment the balance of the fund in life sciences companies, including medical devices companies, at its discretion. The original breakdown called for at least 75% of the fund to be invested in pharmaceutical and biotechnology companies and only 25% in medical devices companies. Israeli venture capital funds that invest in the life sciences did not like this breakdown.

Another difference is that the tender does not stipulate that the fund must channel investment to companies in advanced clinical trials, instead giving more freedom of action to invest in earlier stage companies as well.

The deadline for candidates to submit bids for managing the biotech fund is February 9, 2010, and the winner will be announced on March 1. The preferred candidates are venture capital funds or holding companies. Pharmaceutical companies with more than $500 million annual revenue may not participate in the tender.

Published by Globes [online], Israel business news – www.globes-online.com – on November 11, 2009

Pfizer eyes deal with Israel’s Protalix


Pfizer, the world’s largest drugmaker, is considering a cooperation deal with Protalix Biotherapeutics and may even try to buy the Israeli company, TheMarker financial newspaper said on Monday.

A Pfizer delegation visited the Protalix facilities in Israel last week, TheMarker said.

Protalix officials were not immediately available for comment.

Protalix has a market cap of $726 million and its stock has surged 415 percent so far this year.

Protalix developed the ProCellEx system for producing medical proteins through the genetic engineering of carrot cells. This method is up to 90 percent cheaper than other production methods including the genetic engineering of mammal cells or bacteria, TheMarker said.

Last month Protalix said its experimental drug to treat Gaucher disease, a rare genetic disorder, was successful in a late-stage clinical trial. If approved, the drug, Uplyso, would compete with Genzyme Corp’s biggest-selling drug, Cerezyme.

Protalix is 19 percent held by Israel’s Biocell.

Protalix Chief Executive David Aviezer has said he expects Protalix to sign a partnership agreement with another pharmaceuticals company by the end of this year.

Gamida Cell and Cellerix Partner on Feasibility Study


Gamida Cell and Cellerix Partner on Feasibility Study

cellerix Pre-clinical study will test new method of improving clinical efficacy of expanded populations of adult stem cells obtained from adipose tissue.

Jerusalem, Israel and Madrid, Spain, October 21, 2009 — Gamida Cell Ltd. and Cellerix, S.A. announced today that the companies are collaborating on a feasibility study to evaluate the added value of combining the proprietary technologies of each.

Gamida Cell is developing a series of technologies to expand, ex vivo, populations of stem/progenitor cells that display increased in vivo homing and engraftment activities. The company’s lead product, StemEx®, comprised of expanded populations of adult stem cells derived from umbilical cord blood (UCB), is used today as an experimental treatment for blood cancers like leukemia and lymphoma. The Company anticipates StemEx® will reach the market in 2011.Gamida Cell

Cellerix is developing a new generation of cell-based medicines using expanded adult stem cells (eASCs) obtained from adipose tissue. The Company is also very active developing its allogeneic eASCs platform as 2nd generation products through its Cx611 program for high potential markets. eASCs are a natural medicine with the capacity to activate physiological repair mechanisms through interaction with affected tissue. This technology represents a potential revolution in the treatment of some diseases that cannot satisfactorily be cured at present.

“Gamida Cell is enthusiastic about working with Cellerix, a world class company and an industry leader,” said Dr. Yael Margolin, president and CEO of Gamida Cell. “Gamida Cell’s technologies have demonstrated to improve in vivo functionality of ex-vivo expanded hematopoietic stem cells.  This collaboration seeks to evaluate the feasibility of improving clinical efficacy of ex vivo expanded adult stem cells obtained from adipose tissue

by means of increasing homing and retention following infusion. The results of this study could lead to an entirely new understanding of the widespread application of our various technologies and expand the number of possibilities for Gamida Cell in terms of product development and partnerships.”

“Cellerix has a promising pipeline of cell therapeutics in advanced clinical trials.  Existing data shows that Gamida Cell’s expansion technologies are very effective in hematopoietic stem cells. Combining the technologies of our companies could lead to developing a new line of cell therapeutics.  We are looking forward to seeing the results of this collaboration with an eye on further co-development and commercialization opportunities,” said Eduardo Bravo, CEO at Cellerix.

About Cellerix, S.A.

Cellerix is a biopharmaceutical company with a pipeline of late clinical stage cell therapy products (phase II and III) targeting indications that represent a high unmet medical need.

The company has three products undergoing clinical trials: Ontaril® (Cx401) for the treatment of complex perianal fistulas, currently in Phase III, first medicine expected to reach the market in 2011, Cx501 a cell therapy product for treating epidermolysis bullosa (EB) currently in Phase II and Cx601 consists of a formulation based on donor cells (allogeneic origin) for treating complex perianal fistulas in Crohn’s disease patients now  in phase II. Ontaril®, Cx501 and Cx601 have been designated orphan status by the European Medicines Agency (EMEA). Cellerix has a solid investor base, its ownership structure includes blue chips international VCs and corporate funds from two big pharma companies.

About Gamida Cell

Gamida Cell Ltd. is a world leader in stem cell expansion technologies and therapeutic products. The company is developing a pipeline of products in stem cell transplantation and in tissue regeneration to effectively treat debilitating and often fatal illnesses such as cancer, hematological and autoimmune diseases. Gamida Cell’s therapeutic candidates contain populations of adult stem cells, selected from non-controversial sources such as umbilical cord blood and bone marrow, which are expanded in culture. Gamida Cell was successful in translating these proprietary expansion technologies into robust and validated manufacturing processes under GMP.  Gamida Cell’s first product, StemEx® for blood cancers, is currently being studied in a pivotal registration trial now enrolling patients at leading stem cell transplant centers worldwide (www.stemexstudy.com).

Gene Behind Gaucher Disease a Player in Parkinson’s


By Ed Edelson
HealthDay Reporter

WEDNESDAY, Oct. 21 (HealthDay News) — An unprecedented worldwide study has clinched the case that the gene behind Gaucher disease, a rare neurological disorder, is also involved in Parkinson’s disease.

Gaucher Illustration

Gaucher Illustration

“For those of us who work with rare disorders, it is heartwarming to come up with insights that are applicable to more common disorders,” said Dr. Ellen Sidransky, a senior investigator in the U.S. National Human Genome Research Institute, and leader of a study reported in the Oct. 22 issue of the New England Journal of Medicine.

Gaucher disease affects no more than one in 100,000 people in most populations, with an estimated 5,400 cases in the United States. As many as 3 million to 4 million Americans are estimated to have Parkinson’s disease.

Gaucher disease develops in people who have two defective copies of a gene designated GBA. It codes for production of an enzyme that breaks down glucocerebrosidase, a fatty substance normally found in the body. The faulty gene allows accumulation of the substance, which can harm the spleen, liver, lungs, bone marrow and even the brain.

Discovery that the two conditions have a common genetic element cannot be applied immediately to relieve the stiffness, trembling and other symptoms of Parkinson’s disease, Sidransky said.

“We have to be cautious about jumping into clinical applications,” she said. “This gene plays a more common role in Parkinson’s than other genes, but it is not necessarily predictive of Parkinson’s disease. It is a risk factor rather than a gene that predicts the disease.”

“The work will teach us about the mechanisms of Parkinson’s disease, and once we understand the mechanisms we can come up with therapies that can help patients with Parkinson’s disease. And it could ultimately lead to better therapies that could help patients with Gaucher disease,” Sidransky said.

Several smaller studies have suggested the genetic link between the two conditions, “but there have always been questions based on their size and controls,” Sidransky said. “Once and for all, we have put together a large enough number so that no one will question the results.”

The study she led involved 16 institutions around the world. A listing of the institutions and researchers filled a complete page on the journal in fine print.

Those researchers examined the frequency of GBA variants in 5,691 people with Parkinson’s disease, including 780 Ashkenazi Jews, an ethnic group in which Gaucher disease is more common. Their data was matched with genetic information from 4,898 disease-free individuals, including 387 Ashkenazi Jews.

At least one of two common GBA variants was found in 3.2 percent of the people with Parkinson’s disease, but only 0.6 percent of the disease-free individuals. Among the Ashkenazi participants, 15.3 percent of those with Parkinson’s disease carried a GBA variant, compared to 3.4 percent of disease-free Ashkenazi individuals.

In addition to increasing the risk of Parkinson’s disease, presence of a GBA variant was associated with early onset of the condition, four to five years sooner than ordinarily seen, the study found.

“Its importance is that it may indicate a new pathway to explore for the etiology [cause] of Parkinson’s disease, and ultimately a target for drug discovery,” said Dr. Karen Marder, a professor of neurology at Columbia University Medical Center, and one of the researchers in the trial.

The discovery raises some possible issues about genetic counseling, Marder said, but more work must be done before that can influence medical practice.

“This is among the most important susceptibility factors for Parkinson’s that has ever been discovered, but it is premature to talk about using it in clinical practice,” she said.

More information

Symptoms and treatment of Parkinson’s disease are described by the U.S. National Institute of Neurological Disorders and Stroke.

Eli Lilly Adds Jobs, Plans Cuts


Eli Lilly recently said it plans to cut its workforce to 35,000 by the end of 2011. But a detail in Lilly’s latest earnings announcement shows that the company has actually been moving in the opposite direction this year: The number of worldwide employees rose to 40,800 as of Sept. 30, up from 40,450 at the end of 2008.

The new jobs are largely in China and other emerging markets, Lilly spokesman Mark Taylor told the Health Blog. That’s consistent with a key caveat in Lilly’s job-cut plans — the company says the 35,000 figure excludes “strategic sales force additions in high-growth emerging markets and Japan.”

That means Lilly will continue to add jobs in those markets, even as it cuts jobs in the U.S. and other developed markets. The number of cuts will be greater than the number of new jobs, Taylor said, meaning overall headcount will fall. Beyond that, the company hasn’t given out any details about where the cuts will land.

The overall picture is consistent with what most global pharma players are up to, angling to get into growth markets as fast as possible while slimming down in the developed world, where sales are stagnant.

And even though Lilly added a few hundred jobs overall this year, the company has been shrinking for a while — its total headcount fell by more than 4,000 jobs over the past three years, Taylor noted.



Skin Cells to Predict Cancer Risk


Harry Rubin

Harry Rubin

While some scientists have argued that cancer is such a complex genetic disease that you’d have to sequence a person’s complete genome in order to predict his or her cancer risk, a University of California, Berkeley, cell biologist suggests that the risk may be more simply determined by inexpensively culturing a few skin cells.

Harry Rubin, professor emeritus of molecular and cell biology at UC Berkeley, acknowledges that cancer cells have mutations in hundreds of genes, making it hard to determine which are the key triggers and making prognosis and treatment equally difficult. Even normal tissue differs from person to person because of a myriad of less disruptive mutations and because of different environmental exposures, both of which affect future cancer risk.

But in the September issue of the journal Cancer Epidemiology, Biomarkers and Prevention, Rubin argues that, while it may be hard to dissect the role of each of these mutations, their collective effect should be observable in tissue before any cancers develop.

Specifically, increases in how densely the cells grow, which Rubin argues are a prelude to cancer, may be detectable even before the cancer appears, warning of risks that could be lessened by behavioral changes.

“Over a 50-year career, I’ve worked with cells transforming (into cancer) in culture and seen the first step in a dynamic way, seen cells continuing to multiply when they should have stopped,” Rubin said. “This is the first step in cancer, though not yet cancer, and you can measure these changes quantitatively.”

The problem, of course, is that it is impractical to test all the body’s tissues to determine whether they have abnormal cell growth. But Rubin has found evidence from other studies that, in some cases, skin fibroblasts show these early changes even before cancer appears in other tissues, such as the colon.

“The abnormal growth behavior of skin fibroblasts in cancer-prone individuals has suggested that, at least in some cases, cancer can be considered a systemic disease and that this difference in the behavior of skin fibroblast cells from such individuals may be a practical basis for prevention, diagnosis and management of the disease,” he concluded in his paper.

“It’s a great idea, scientifically; the question is, ‘Is it there clinically?'” said Douglas Brash, professor of therapeutic radiology, genetics and dermatology at Yale School of Medicine. “This is interesting enough that someone should look to see whether it is clinically reliable.”

Dr. Stuart H. Yuspa, co-chief of the Laboratory of Cancer Biology and Genetics at the National Cancer Institute, agreed. “Harry’s ideas are always amazing, and I admired the paper,” he said. “His idea has scientific support, and if it turned out to be correct, it could be extremely valuable for people, assuming they would want to know their risk.”

Rubin bases his argument on various studies over the past 50+ years that show that cancers grow from a larger “field” of abnormally multiplying cells that otherwise look normal. These “field” cells are generally ignored by surgeons when they remove solid cancers – in fact, the large size of the field would make its total removal impossible – but pathologists have shown that the cells are capable of again giving rise to cancers.

“These cells have early mutations that could lead to cancer,” Rubin said. “Even though they look normal, they multiply in places where they shouldn’t and eventually accumulate enough mutations to form a carcinoma. They are the first stage in cancer, but not cancer.”

The inappropriate growth – called cancerization – is a sign that the normal processes that stop growth when cells contact one another have been disrupted, though not fully, because otherwise the cells would invade the underlying connective tissue and become cancerous.

Rubin showed in experiments 15 years ago that if you take cells that grow normally in cell culture and encourage mutations, then select for behavioral abnormalities involving growth, you can get proliferation of cells that behave like cancerization field cells.

Similarly, while normal skin fibroblast cells grow to a certain density and stop, fibroblasts from cancer-susceptible individuals grow to an unusually high density in a Petri dish. That difference between fibroblasts from normal and cancer-susceptible individuals can be amplified to improve identification of those at risk of cancer, Rubin said.

Rubin suspects that the growth change in skin fibroblasts heralds a general change in all the body’s epithelial tissue, that is, the tissues that line all the body organs. The most prevalent cancers – including colon, breast, lung, skin, head and neck – arise from epithelial tissue. In certain cancer-prone families, for example, the same mutated gene is found in all tissues, and the fibroblasts grow to high densities in culture, just like epithelial cells in a precancerous field do in the body.

“If this works out after studying a large number of cases, then the people who are found to have a high probability of developing cancer would be more likely to pay attention to their diet, exercise, weight, smoking and behaviors that are known to contribute to an increased risk of cancer,” he said. “Basic studies of a cell culture model for field cancerization should reveal the conditions that drive or delay the process and could be applied in prevention of cancer.”

Date: October 15, 2009
Source: University of California – Berkeley

Merck’s GARDASIL Approved For Males


Merck & Co., Inc. announced that the U.S. Food and Drug Administration (FDA) has approved GARDASIL [Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine, Recombinant] for use in boys and men 9 through 26 years of age for the prevention of genital warts caused by human papillomavirus (HPV) types 6 and 11.  FDA approval is the first step in an important two-step process.  The next step in the process is an Advisory Committee on Immunization Practices vote on whether to recommend administration of GARDASIL for use in males, as well as public funding through the U.S. Centers for Disease Control and Prevention (CDC) contract.  These votes are expected on October 21.

“We are pleased that GARDASIL is now available to help protect males,” said Richard M. Haupt, M.D., MPH, executive director, Merck Research Laboratories.  “This is an important milestone, because the use of GARDASIL can now help protect boys and girls and young men and women from certain diseases caused by this common virus.”  Approximately 75-80 percent of people acquire one or more types of HPV at some point in their lives.  For most people, the virus will go away on its own.  But, for some people who don’t clear certain types of the virus, HPV diseases can develop, and there is no way to predict who will or won’t clear the virus. According to the CDC, certain types of HPV are associated with precancers and cancer, including cervical, vulvar, and vaginal cancers in women.  In addition, other HPV types cause genital warts in both women and men.

“Nearly 17,000 new cases of genital HPV infection, of any type, occur each day in the United States, in both males and females,” said Anna Giuliano, Ph.D., H. Lee Moffitt Cancer Center, Tampa, Florida.  “While most of these HPV infections clear on their own, this year alone, it is estimated that one million people in the U.S. will develop genital warts, which can cause discomfort and be distressing.  Some resolve without treatment; but, for those that require treatment, warts recur in at least 25 percent of cases.”

GARDASIL helps protect against the four types of HPV, specifically types 6, 11, 16, and 18 that cause the most disease.  It is estimated that HPV types 16 and 18 account for

70 percent of cervical and vaginal cancer cases and up to 50 percent of vulvar cancer cases.  Types 6 and 11 cause approximately 90 percent of all genital warts cases.

“Education about the prevalence of HPV infection and potential disease consequences, along with the benefits and limitations of vaccination with GARDASIL, is important,” says Giuliano.  “As with all vaccination programs, important factors in successful implementation include patient education, along with clear communications by health care professionals.”

GARDASIL was approved in 2006 and is indicated for use in girls and young women 9 through 26 years of age for the prevention of cervical cancer, vulvar cancer, and vaginal cancer and pre-cancers caused by HPV types 16 and 18; genital warts caused by HPV types 6 and 11; and precancerous or dysplastic lesions caused by HPV types 6, 11, 16, and 18.  GARDASIL is contraindicated in individuals with hypersensitivity, including severe allergic reactions to yeast, or after a previous dose of GARDASIL.

Date: October 16, 2009
Source: Merck & Co., Inc.

Faster, Cheaper Stem Cells: Fate Therapeutics Co-Founder, With Scripps Team, Finds Key


Luke Timmerman

One of the scientific co-founders of San Diego-based Fate Therapeutics, along with his team at The Scripps Research Institute, is reporting a major advance that will make it faster, cheaper, and potentially practical on an industrial scale to turn adult cells into stem cells that can morph into any type of cell in the human body.

Sheng Ding and his colleagues at Scripps have found a combination of three conventional small-molecule chemical compounds that can coax a

Rudolf Jaenisch, professor of biology

Dr. Rudolf Jaenisch from Fate Therapeutics

dult human cells into an embryonic-like state. The new technique is about twice as fast as existing methods, and produces 200 times more cells per batch. The research in how to efficiently make these so-called “induced pluripotent stem cells” was sponsored by Fate, and is being published online today in the journal Nature Methods.

The technology, which is exclusively licensed to Fate through its sponsored research agreement with Scripps, is a big feather in the cap for the startup

company as it seeks to strike deals with pharmaceutical and biotech companies that are looking get into the stem cell game. Fate has been a leader in the field since its founding two years ago by a group of top stem cell scientists from Harvard University, the University of Washington, Stanford University, and Scripps. One of those co-founders was Ding, a young scientist who got his first faculty post in 2003 at Scripps.

“This is the first example in human cells of how reprogramming speed can be accelerated. I believe that the field will quickly adopt this method, accelerating [induced pluripotent stem cell] research significantly,” Ding said in a statement from Scripps.

The latest advance builds on the discoveries of Shinya Yamanaka of Kyoto University and James Thomson of the University of Wisconsin, who showed for the first time two years ago that scientists could transform adult human cells into a pluripotent state, like that of cells in an early embryo. That was important because it was a way to circumvent the political and ethical controversy over destroying embryos in order to harvest their stem cells for research.

Pioneering as that work was, it was nowhere near ready for prime-time use in the biotech and pharmaceutical industries. Yamanaka and Thomson used viruses to insert multiple copies of four genes into adult cells. Two of the genes are known to cause cancer. Given that risk, it’s almost impossible to imagine regulators ever allowing cells with that kind of genetic modification to be injected into people who want to, say, regenerate new pancreas cells to treat their diabetes. The other big problem with the original method was that it took four weeks from start to finish, and only worked in about one out of every 10,000 cells.

Today’s announcement is the second big stem cell paper this year from the Ding lab. In May, the Ding lab reported that it had essentially gotten around the first technical challenge with genetic modifications. Ding and his colleagues discovered a way to use genetically engineered protein drugs that could coax adult cells into a pluripotent state without the danger of using cancer-causing genes delivered by viruses. That work was published in the journal Cell Stem Cell.

Five months later, Ding has taken another big step ahead that could make stem cell research much more practical for pharmaceutical companies, says Fate Therapeutics CEO Paul Grayson. As anybody who follows the biotech industry knows, genetically engineered protein drugs—like Amgen’s etanercept (Enbrel) or Eli Lilly’s cetuximab (Erbitux)—are expensive to manufacture. Essentially, using proteins like that to induce a pluripotent state would be cost-prohibitive for what Fate wants to do. That’s why Ding’s team went on a search for small molecules that would do the job.

Fate envisions using induced pluripotent stem cells—at least in the early days of the field—primarily to support basic research into the discovery of new drugs. The rationale is that if you can create new neurons in a lab dish that are like neurons harvested from the human brain, then that could be a very useful platform for testing new drugs designed to deter or reverse the changes associated with Alzheimer’s, multiple sclerosis, or Parkinson’s. Further in the future, induced pluripotent stem cells that have been made to differentiate into neurons might be injected into people as regenerative treatments.

So if Fate is going to create a method for churning out these valuable induced pluripotent cells, it will have to be fast, cheap, and reproducible, like all good industrial processes. That’s why Ding’s paper today is so important, Grayson says. Small molecule compounds are really cheap and readily available compared with genetically engineered proteins.

“This is Sheng’s next big leap forward,” Grayson says. “It makes the whole process much more efficient.” With small molecules, Grayson adds: “We’re talking about dollars per gram instead of tens of thousands of dollars,” as with genetically engineered proteins.

But the researchers aren’t getting carried away with excitement; lots of big challenges remain. One of the critical ones is with what scientists call “heterogeneity,” which essentially means they need to make sure they’re getting consistent results. For example, the FDA would want to be absolutely certain that induced pluripotent stem cells can be differentiated into, say, neurons with uniform consistency, so that it knows exactly what is being injected into a person.

Fate isn’t trying to pretend that it has the process of making induced pluripotent stem cells completely nailed for pharmaceutical industry grade experiments. “As Rudy Jaenisch has said, you can wait for it all to be figured out and miss the boat, or you can work on it now and help shape it,” Fate spokeswoman Jessica Yingling told me last month, citing remarks by MIT and Whitehead Institute biologist Rudolf Jaenisch, an advisor to Fate.

It will be very interesting to see if this latest paper by Ding, and the speed and efficiency gains it may represent, will be enough to get Big Biotech and Big Pharma to jump on the bandwagon with Fate, and start to help shape it, to use Jaenisch’s phrase. After all, Fate has raised $25 million in capital since its founding, and it is growing fast. With ambitions like this, it will definitely need more capital. Grayson was a bit cagey about what the new results mean for his ability to do deals with pharma companies, but he did say, “It’s great for the field, and for Fate Therapeutics in our relationship with Big Pharma.”

Luke Timmerman is the National Biotechnology Editor for Xconomy

Compound Shows Potential For Slowing Progression Of Lou Gehrig’s Disease


ALSScienceDaily (Oct. 20, 2009) — A chemical cousin of a drug currently used to treat sepsis dramatically slows the progression of amyotrophic lateral sclerosis, better known as ALS or Lou Gehrig’s disease, in mice. The results offer a bit of good news in efforts to develop a therapy to stop or slow the progression of a disease that generally kills its victims within just a few years.

In a paper published online Oct. 19 in the Journal of Clinical Investigation, scientists studied the use of a form of an enzyme known as activated protein C, or APC, to slow the cell death that occurs in ALS. They were able to extend the lifespan of mice with an aggressive form of the disease significantly, by about 25 percent. The compound also extended the length of time that the mice were able to function well despite showing some symptoms of the disease, and it reduced the pace of muscle wasting that is a hallmark of ALS.

While the investigators say that more research must be done before the enzyme is tested in people with the disease, they are encouraged that the work involves a compound that has already been proven to be safe and is currently given to patients via a common injection for another condition. The team hopes to test a treatment in patients within five years.

The work was done by investigators from the University of Rochester Medical Center, the University of California, San Diego School of Medicine, The Scripps Research Institute in La Jolla, University of Notre Dame, and a Rochester-based start-up biotech company, Socratech.

Corresponding author of the study is neuroscientist Berislav Zlokovic, M.D., Ph.D., of the University of Rochester Medical Center, whose group collaborated with laboratories led by Don Cleveland, Ph.D., a widely recognized ALS expert at UC San Diego, and John Griffin, Ph.D., an APC expert at Scripps. First authors of the paper were Instructor Zhihui Zhong of Rochester and post-doctoral associate Hristelina Ilieva of UC San Diego.

The research involved mice with a mutation in a gene known as superoxide dismutase 1 (SOD1), which plays an important role keeping cells safe from damaging molecules known as free radicals. While the cause of most cases of ALS is unknown, scientists do know that SOD1 plays a role in approximately 3 or 4 percent of cases – providing an opportunity to study the disease’s initial steps, which occur long before key nerve cells appear sick or die. In addition, recent studies have suggested that the accumulation of mutant forms of SOD1 is linked to most sporadic cases of ALS.

Cell death is central to the symptoms of ALS, a chronic disorder of motor neurons in the brain, brainstem and spinal cord which results in a progressive paralysis that generally kills individuals within five years of onset. Currently there is no cure or even a treatment that can effectively slow disease progression.

In a surprising finding last year, a team led by Zlokovic and Cleveland found that SOD1 mutations weaken the crucial natural barrier between blood and the spinal cord. In effect, blood vessels in the spinal cord become leaky, allowing toxic substances to flood into the spinal cord. Because of the defect, motor neurons are exposed directly to biochemical byproducts of hemoglobin such as iron, which forms reactive oxygen molecules that injure or kill neurons.

Now, the team has shown that APC dramatically lessens the activity of the SOD1 mutation. This protects neurons that are under assault by blocking the synthesis of aberrant forms of the molecule in motor neurons and other cells in the spinal cord. These include microglia cells, which the Cleveland laboratory has shown play a key role in the inflammatory response and progression of ALS. In addition to reduced SOD1 activity, the flow of dangerous byproducts of hemoglobin into the spinal cord was eliminated by APC, saving neurons.

Currently the group is studying alternate forms of APC, in an effort to create the form that best quells the symptoms of ALS while causing few unwanted side effects, such as bleeding. Zlokovic says the form of APC currently used to treat sepsis carries an increased risk of bleeding and likely will not be appropriate for treating ALS in humans.

While other researchers are exploring the possibility of silencing SOD1 to treat ALS, Zlokovic notes that most approaches would require invasive surgery and delivery by direct infusion into the spinal cord. APC, in contrast, is already approved as an injection.

“The success of this research project has been very gratifying, and we are hopeful that a form of APC will ultimately be useful as a treatment for this disease,” said Zlokovic, who is professor of Neurosurgery and Neurology and director of the Center for Neurodegenerative and Vascular Brain Disorders at Rochester.

“I began this line of research at the request of an old friend – a childhood pal with whom I was friends my whole life, until he got ALS and died just a few years later. It was very sad. Clearly, something has to be done – new treatments are needed,” added Zlokovic.

Zlokovic and Griffin are named as inventors on several patents and applications related to APC, and Zlokovic is the founder of ZZ Biotech, a company developing new treatments for stroke and Alzheimer’s disease. Zlokovic and the University both hold a stake in ZZ Biotech and Socratech.

Other authors include Lee Hallagan, Robert Bell, Itender Singh, Nicole Paquette, Meenakshisundaram Thiyagarajan, Rashid Deane, Steven Lane, Anna Zlokovic, Todd Liu and Konstantin Stojanovic of the University of Rochester; Jose Fernandez of Scripps; Nienwen Chow of Socratech; and Francis Castellino of Notre Dame. The work was funded in part by the National Institutes of Health.


Journal reference:

  1. Zhong et al. Activated protein C therapy slows ALS-like disease in mice by transcriptionally inhibiting SOD1 in motor neurons and microglia cells. Journal of Clinical Investigation, 2009; DOI: 10.1172/JCI38476
Adapted from materials provided by University of Rochester Medical Center.

Scientists demonstrate link between genetic defect and brain changes in schizophrenia


 

CHAPEL HILL For decades, scientists have thought the faulty neural wiring that predisposes individuals to behavioral disorders like autism and psychiatric diseases like schizophrenia must occur during development. Even so, no one has ever shown that a risk gene for the disease actually disrupts brain development.

Anthony LaMantia

“For practically ever other disease, we know what cells take a hit,” said senior study author Anthony LaMantia, Ph.D., professor of cell and molecular physiology and co-director of the Silvio M. Conte Center for Research in Mental Disorders at the UNC School of Medicine.

Now, researchers at the University of North Carolina at Chapel Hill School of Medicine have found that the 22q11 gene deletion a mutation that confers the highest known genetic risk for schizophrenia is associated with changes in the development of the brain that ultimately affect how its circuit elements are assembled

In studies conducted in mice, the researchers discovered that the genetic lesion alters the number of a critical subset of neurons that end up in the brain’s cerebral cortex the region critical to reasoning and memory. The defect also causes another type of nerve cell called GABAergic neurons to be misplaced within the brain’s cortical layers, resulting in a subtle miswiring of the organ.

“For practically ever other disease, we know what cells take a hit,” said senior study author Anthony LaMantia, Ph.D., professor of cell and molecular physiology and co-director of the Silvio M. Conte Center for Research in Mental Disorders at the UNC School of Medicine. “For multiple sclerosis the myelinating oligodendrocytes in the brain falter, for Lou Gehrig’s disease the motor neurons in the brain stem degenerate. But we really had no idea what was happening in schizophrenia, or in any of the psychiatric diseases for that matter until now.”

His study will be presented Oct. 17 at the Society for Neuroscience meeting in Chicago, by Daniel Meechan, Ph.D., post-doctoral fellow in the LaMantia laboratory and the first author of a recent paper in Proceedings of the National Academy of Sciences that details the findings.

The study lends the first clear support to the “neurodevelopmental hypothesis” a scientific theory LaMantia calls the “Hail Mary” of schizophrenia pathologists.

For many years, researchers searched in vain for any indication that the brains of patients with schizophrenia were different from normal subjects –for some laboratory finding along the lines of the plaques and tangles characteristic of Alzheimer’s disease or the degeneration of dopamine cells that are the calling card of Parkinson’s disease. Similar degenerative change has never been identified for schizophrenia. Finally they proposed that the defects in schizophrenia must arise before the brain is fully formed, rather than after.

Then researchers began to discover regions of the genome — many of which had neurodevelopmental functions — that made people susceptible to schizophrenia.

In this study, LaMantia and his colleagues decided to pursue deletion of one such region on human chromosome 22, which causes DiGeorge syndrome in humans, because it is the single best-defined genetic lesion associated with schizophrenia. They tracked two subclasses of neural stem cells — called basal and apical progenitors — throughout early brain development in a mutant mouse with the same genetic deletion. They found that the basal progenitors divided more slowly than they should, and as a result the cells that they give rise to in the cortex were not generated in the proper numbers.

The researchers also looked at another population of cells, the GABAergic cells that are thought to essentially put the brakes on electrical activity in mature cortical circuits. The function of these cells is believed to be one of last processes to be disrupted in the schizophrenic brain. LaMantia found that these GABAergic neurons never made their way to their correct positions in the cortical layers of the brain of the mouse model of DiGeorge Syndrome .

The researchers would now like to figure out how these alterations in the circuitry of the brain affect the behavior of the mouse. They also hope that understanding the “mis-wiring” of the brain in a genetic animal model of schizophrenia would help them understand the causes of the disease in the general population.

“Now that we know what cells can be affected in schizophrenia, it opens up new avenues in thinking about the molecular mechanisms underlying this and other psychiatric illnesses,” said LaMantia. “We can even begin to look for biomarkers of the disease that can be used for better diagnosis and treatment.”

 

Contact: Les Lang

llang@med.unc.edu

919-966-9366

University of North Carolina School of Medicine

 

Funding for the studies led at UNC came from the National Institutes of Health and the Silvio M. Conte Center. Study co-authors from LaMantia’s laboratory at UNC include postdoctoral fellows Daniel W. Meechan, Erin S. Tucker and Thomas M. Maynard.

GEN_logo

 

Biotechs Back From The Dead


Matthew Herper, 10.16.09, 6:00 AM ET

Just a year ago, it seemed a near certainty that the global financial crisis was going to decimate the biotechnology industry.

In January, half of 370 small biotech firms had less than a year of cash, according to the Biotechnology Industry Organization. Seventy biotech stocks were trading at less than $1 a share. Yet financing was hard to come by, with no new initial public offerings. In March, Stephen Brozak at WBB Securities warned of “zombie biotechs,” companies without the financial wherewithal to get research done.

But biotech didn’t die off–it came roaring back. A Forbes screen of the industry shows that 50 companies that traded for less than $1 a share in the past 52 weeks now trade for at least $2, and 30 of them sport market capitalizations of more than $100 million–13 have ballooned to more than $200 million. Ten have seen a price increase of 1,000% or more, although most still count as risky micro-caps.

What happened? For the most part, the same thing that always saves biotechnology companies: luck. More specifically, “binary events” like clinical trial results, regulatory approvals and other signs that moribund products might sell turned these companies around.

Human Genome Sciences, which just months ago traded for 50 cents a share, is now at $19.50 thanks to blowout results for its lupus drug Benlysta, an increase of more than 4,000%. Before that, the smart money was on failure.

Vanda Pharmaceuticals had gotten a “not approvable” letter from the FDA for its antipsychotic, but managed to get the FDA to change its mind. Then, this week, it sold the rights to the drug to Novartis for milestones and a royalty. It’s up 2,000%.

Jazz Pharmaceuticals has rocketed more than 1,000% on data that its narcolepsy drug Xyrem may work in fibromyalgia.

The most amazing comeback is that of Vermillion, a tiny developer of diagnostic tests that is still in Chapter 11 bankruptcy. The company, which developed a blood test called OVA1 to measure the likelihood that ovarian tumors are malignant, was facing worries about whether it could pay bondholders before the financial crisis hit. Its stock was delisted from the Nasdaq on Sept. 26, 2008.

Vermillion filed for bankruptcy protection on March 30, 2009, when it had less than $1 million in cash left. The entire executive team resigned to save cash, continuing to work on a consulting basis. The board took payment in equity. Only three employees–one in regulatory affairs, one in quality control, and one to handle financial affairs–remained on the payroll. Gail Page, the company’s executive chairman, says the only way she could keep the company alive was to put it in suspended animation.

On Sept. 11, 2009, the Food and Drug Administration cleared the OVA1 test, and Vermillion shares began to rocket upward on the Pink Sheets. Quest, Vermillion’s marketing partner, gave Vermillion $1.5 million in funding and said it wouldn’t demand that a $10 million loan made in 2005 be paid off immediately. Its shares are up 180,000% from their 52-week low. Page says her investors include Quest and the family of biotech giant George Rathmann.

Vermillion is still a bankrupt company trading on the Pink Sheets, with all the risks that implies. Right now, it doesn’t have an estimate for the potential market for the OVA1 test. The company has until Nov. 29 to file a plan of reorganization. Eventually, it hopes to re-emerge on the Nasdaq.

Not every company has escaped. Some, like genomics firm DeCode Genetics, are still living on as hobbled stock. Others, like brain drug maker Memory Pharmaceuticals, got bought up cheap. (In Memory’s case, the buyer was Roche.)

Brozak, the analyst who warned of biotech zombies, notes that Big Pharma’s troubles are keeping biotech valuations up. He points to Johnson & Johnson’s $1 billion purchase of Cougar Biotechnology as one of the deals that keep biotech investors hoping that their stock will get acquired, too.

Phoenixes Or Flukes?
These biotech companies were all recently penny stocks, but now have market capitalizations of more than $100 million after price increases of 1,000% or more.
Company Name Recent Price Market Capitalization (Millions) 52-Week Low Increase (%)
Vermillion Inc. 18 100.8 0.01 179900
Human Genome Sciences Inc. 19.42 3,118.30 0.45 4216
Vanda Pharmaceuticals Inc. 11.88 313 0.45 2540
Keryx Biopharmaceuticals Inc. 2.24 127.4 0.09 2389
Jazz Pharmaceuticals Inc. 8.66 241.4 0.52 1582
Winner Medical Group Inc. 6.08 130.8 0.38 1500
Ista Pharmaceuticals Inc. 4.42 138.5 0.29 1424
Helicos BioSciences Corp. 2.64 194.1 0.21 1157
Antigenics Inc. 2.15 186.4 0.19 1032
BioCryst Pharmaceuticals Inc. 9.47 352.4 0.85 1014

Sources: Interactive Data and Reuters Fundamentals via FactSet Research Systems.

Pfizer May Cut $3 Billion in Research With Wyeth Deal


By Shannon Pettypiece and Andrea Gerlin

Oct. 15 (Bloomberg) — Pfizer Inc. may slash as much as $3 billion in research after combining its laboratories with Wyeth, putting thousands of scientists out of work and narrowing the drugmaker’s search for new products.

With the $68 billion deal closed, Pfizer will probably trim its combined research budget, Martin Mackay, president of Pfizer Global Research and Development, said in an interview. While Mackay didn’t say by how much, Pfizer may hold the line at about $8 billion, the same as it spent by itself in 2008, said Barbara Ryan, a Greenwich, Connecticut-based analyst for Deutsche Bank, in a telephone interview. That’s 30 percent less than the total both companies spent on research last year.

Pfizer has trimmed jobs and limited the diseases it studies in the last two years to save money as it braces for the loss of $10 billion in sales when its Lipitor cholesterol pill faces generic competition in 2011. While Pfizer Chief Executive Officer Jeffrey Kindler said he bought Wyeth to help offset those losses, the drugmaker’s ability to innovate over time may be diminished with fewer scientists to find new treatments, said Kenneth Kaitin, of Tufts University in Medford, Massachusetts.

“These big acquisitions don’t do a thing for research,” said Kaitin, director of the Tufts Center for the Study of Drug Development. “I don’t think anyone should be fooled into thinking these big acquisitions have anything to do with innovation or increased research and development capacity.”

Nine Areas

Pfizer, the world’s biggest drugmaker, has narrowed its drug-development focus to nine disease areas led by cancer, brain disorders and diabetes. It has trimmed its scientific programs on heart failure, high cholesterol and obesity. The New York-based company also reorganized its research centers so that each area of therapeutic research is based at one location.

Over the short term, Pfizer is close to meeting its goal of having 24 to 28 products in late-stage development by December, Mackay said in an Oct. 2 interview. That includes a pill developed for rheumatoid arthritis, CP- 690550, which could generate $1.5 billion annually, said Cowen & Co. analyst Craig Gordon. Existing treatments for that disease are injected.

Such late-stage products, though, have been years in development. Since 2007, the company has fired more than 2,000 researchers and closed laboratories in Michigan, Japan and France. While the Wyeth purchase may help Pfizer offset the loss of Lipitor revenue initially, the research cuts may challenge the combined company’s long-term growth, Kaitin said.

“This is just a delaying tactic, it doesn’t increase output in terms of research,” Kaitin said. “This is a survival technique for big pharma.”

Joint Operations

Pfizer and Wyeth will begin joint operations tomorrow, Pfizer said today in a statement. Wyeth shares will stop trading today and each outstanding share of Wyeth will be converted to $33 in cash and 0.985 of a Pfizer share.

Moody’s Investor Services lowered its long-term rating of Pfizer to A1 from Aa2. Fitch Ratings dropped Pfizer’s long-term issuer default rating to AA- from AA.

Mackay, in an interview at the company’s Sandwich, England, laboratories, said that while no final figure has been reached, the combined research budget would be reduced. The drugmaker will review projects in the next six weeks, said David Roblin, who heads the Sandwich laboratory where Viagra, Pfizer’s top- selling erectile drug, was invented.

Scientists at the two companies aren’t permitted to exchange information about their work until the merger is completed, and are “desperate” to talk, Roblin said Oct. 2.

“As soon as the close happens, the phones will be red hot,” Roblin said. “It’s an exciting time for scientists because there’s nothing like new data.”

Potential Targets

The company looked at more than 100 potential acquisitions before deciding to buy Wyeth, Mackay said. The merged company, he said, will focus on cancer, pain, neurological disorders, heart and circulatory diseases, diabetes, infectious diseases and antibacterials and vaccines.

Pfizer rose 29 cents, or 1.7 percent, to $17.66 at 4:15 p.m. in New York Stock Exchange composite trading after announcing the acquisition would be completed today. Pfizer has gained 8.7 percent in the past 12 months.

Pfizer is not alone in scaling back research spending to combat sinking revenue from cheaper copy drugs. Products that now generate $137 billion in sales are expected to face generic competition during the next five years, said IMS Health Inc.

Industry Job Cuts

Johnson & Johnson, based in New Brunswick, New Jersey, said this week its research budget fell 13 percent in the third quarter compared with a year earlier. British drugmaker AstraZeneca Plc has slashed at least 700 research positions and GlaxoSmithKline Plc, also based in London, said last year it planned to eliminate as many as 850 researchers.

The proportion of sales that pharmaceutical companies spend on research may sink to 13 percent next year, from 16 to 18 percent of sales, Ryan said.

Spending cuts have resulted in a flood of scientists into the job market, said Michael Steiner, who provides financial and career counseling to pharmaceutical professionals at RegentAtlantic Capital LLC in Morristown, New Jersey. Steiner said he has more than 100 pharmaceutical clients. Many who have lost their jobs are considering teaching, consulting or working at small biotechnology companies.

Job openings at large pharmaceutical firms are scarce, and some of his clients have been looking for work for more than a year, he said.

High School Chemistry Teachers

“Pretty much all the high school chemistry jobs have been filled,” said Steiner in a telephone interview. “Some of these are people who have been at a company for more than 25 years and are now entering the job market for the first time.”

Most pharmaceutical researchers need a Ph.D. in biology or chemistry and some have medical degrees, according to the U.S. Bureau of Labor Statistics. Drugmakers also employ laboratory technicians and support staff, jobs that typically require a high school diploma or an associate degree.

In Ann Arbor, Michigan, where Pfizer closed its 2,100- person laboratory in 2008, more than a dozen ex-Pfizer employees have taken jobs at the nearby University of Michigan, the school said in 2008. Among them is Michael Wilson, who started working as a pharmaceutical researcher at Warner Lambert Co. 25 years ago on development of Lipitor, now the world’s best-selling medicine with $12.4 billion in 2008 revenue. Pfizer bought Warner Lambert in 2000.

Former Pfizer employees displaced by lab closures in Ann Arbor and Kalamazoo, Michigan, have formed at least 44 companies, according to economic development groups Ann Arbor Spark and Southwest Michigan First.

New Venture

One such company, Kalexsyn Inc., was founded by two chemists fired by Pfizer when it bought Pharmacia Corp. in 2003. Kalexsyn provides contract chemistry work and early stage laboratory research for pharmaceutical companies.

Pfizer said in January it would fire 19,000 workers, about 15 percent of the merged drugmakers’ 129,500 employees. That is in addition to the more than 14,000 positions it has eliminated since 2007. Madison, New Jersey-based Wyeth spent $3.4 billion on research in 2008 and has about 6,000 researchers. Pfizer spent $7.9 billion last year with about 10,000 scientists.

Following the Wyeth acquisition, Mackay and Mikael Dolsten, now president of Wyeth research, will divide executive responsibility for research and development at the combined company. Mackay will oversee traditional research into chemicals and Dolsten will guide development of biotechnology products derived from living cells.

Wyeth Officers Retained

“I’ve known Mikael Dolsten for some time and I’m a great admirer,” Mackay said. “The notion of us both running this organization just made a lot of sense.”

Nine chief scientific officers have been appointed to lead therapeutic and technical areas of the company’s R&D, some retained from Wyeth, Mackay said.

Mackay said he expects scientific collaborations with external partners to continue once the merger is completed.

“I don’t think we’re going to aim for the Pfizer culture or the Wyeth culture or any legacy company,” Mackay said. “To make this work in this two-division model with Mikael and I running it, collaboration is going to be at the forefront.”