Kerentech

$ 1.1 B Agreement  beetwen Roche and Aileron

Aileron Therapeutics and Roche  announced today that they have entered into a collaboration to discover, develop 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, which include oncology, virology, inflammation, metabolism and CNS.

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.

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, regulatory 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. For more information: www.aileronrx.com.

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. For more information:

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.

“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 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 upon 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.

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

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.

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.

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.

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.

A Global License and Research Collaboration Agreement on compounds designed to restore the p53 tumor suppressor function in cancer cells
Ascenta 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.

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.”