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Bristol-Myers Squibb and ZAI Lab Enter Licensing Agreement to Develop,Manufacture and Commercialize Brivanib in China

On March 23, 2015 Bristol-Myers Squibb Company (NYSE: BMY) and ZAI Lab Limited (ZAI Lab), a leading innovative biotech company based in China, reported that the companies have signed a definitive agreement under which ZAI Lab will acquire exclusive rights in China (including Hong Kong and Macau) to develop, manufacture and commercialize brivanib, an orally available kinase inhibitor in Phase 3 development for oncology indications including hepatocellular carcinoma (HCC).

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ZAI Lab will be responsible for developing, manufacturing and commercializing brivanib in China. Bristol-Myers Squibb will be eligible to receive developmentbased milestone payments and tiered royalties from the commercial sales of brivanib in China, if brivanib is approved for marketing by Chinese authorities. Bristol-Myers Squibb also will have the option to co-promote brivanib in China with ZAI Lab and share commercial profits. Bristol-Myers Squibb retains all development and commercialization rights to brivanib outside of China, Macau and Hong Kong. Additional terms were not disclosed.

"HCC is the most common form of primary liver cancer and patients with intermediate-stage HCC typically live only 20 months after diagnosis on average," said Karl Lintel, president, Bristol-Myers Squibb China. "We are pleased to partner with ZAI Lab to further investigate brivanib as a potential treatment for patients living with HCC in China. Earlier studies of brivanib in this patient population suggest brivanib may be an effective therapy, prolonging time to progression to advanced disease for patients who have no other effective treatment options."

Samantha Du, Ph.D., founder and CEO of ZAI Lab said: "We are very excited about this agreement. Brivanib has already been tested in multiple global Phase 3 studies with a large number of Chinese HCC patients participating in the trials. Encouraging
efficacy data have been observed among the Chinese HCC patients with an acceptable safety profile. China accounts for more than 50% of global annual incidence of liver cancer, with more than 400,000 new cases and 371,000 deaths in 2012. Based on the
preliminary analysis of the extensive Phase 3 data, brivanib may offer a new treatment option for Chinese HCC patients."

Pfizer And Lilly Preparing To Resume Phase 3 Chronic Pain Program For Tanezumab

On March 23, 2015 Pfizer Inc. and Eli Lilly and Company reported that they are preparing to resume the Phase 3 clinical program for tanezumab (Press release, Eli Lilly, MAR 23, 2015, View Source;item=137402 [SID:1234513834]). As a result, Pfizer expects to receive a $200 million upfront payment from Lilly in accordance with their collaboration agreement. This announcement follows a decision by the U.S. Food and Drug Administration (FDA) to lift the partial clinical hold on the tanezumab development program after a review of a robust body of nonclinical data characterizing the sympathetic nervous system response to tanezumab. The data were submitted to the FDA in February 2015.
In the prior clinical studies of more than 11,000 patients, tanezumab demonstrated clinically meaningful efficacy vs. placebo and other select commonly used pain medicines. A partial clinical hold has been in place for tanezumab and all other anti-nerve growth factor antibodies since December 2012 due to adverse changes in the sympathetic nervous system of mature animals. Studies in terminal cancer pain were allowed to proceed.

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"We are pleased with the FDA’s decision as chronic pain remains an area of significant unmet medical need and we believe tanezumab has potential to offer a new, non-narcotic option," said Steve Romano, MD, senior vice president and head of Global Medicines Development at Pfizer’s Global Innovative Pharmaceuticals Business.

"We’re pleased to work with Pfizer to resume the Phase 3 program, and we’re confident that tanezumab, if approved, can be an innovative treatment with the potential to help millions suffering from painful conditions," said David Ricks, Lilly senior vice president and president, Lilly Bio-Medicines.
It is estimated that nearly one in five adults suffer from chronic pain.

About Tanezumab
Tanezumab is a humanized monoclonal antibody that selectively targets nerve growth factor (NGF), a regulator of pain processing and sensitivity. NGF levels increase as a result of injury or inflammation and in chronic pain states. Tanezumab selectively binds to NGF, thereby inhibiting this protein from activating pain-signaling neurons.

FORMA THERAPEUTICS AND CANCER RESEARCH TECHNOLOGY FORM TWO VIRTUAL COMPANIES TO ADVANCE DEUBIQUITINATION ASSETS

On March 23, 2015 FORMA Therapeutics and Cancer Research Technology, Ltd. (CRT) reported the formation of two new virtual Asset Discovery and Development Companies (ADDCos) with novel chemical matter targeting undisclosed deubiquitinating enzymes (DUBs) (Press release, Forma Therapeutics, MAR 23, 2015, View Source [SID:1234509334]). ADDCos are virtual companies seeking to achieve rapid innovation in a compelling scientific area through the collaboration of academic thought leaders, FORMA drug discovery scientists and a world class development network.

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This builds on an ongoing initiative between FORMA and CRT, the commercial arm of Cancer Research UK, to discover innovative tools, technologies and therapeutic drug candidates against a variety of DUBs that regulate protein homeostasis. Under their agreement, FORMA is pairing its ultra-efficient drug discovery capabilities with expertise from CRT’s Discovery Laboratories (CRT-DL) in translating academic discoveries and the exclusive world class academic network of Cancer Research UK scientists.

Protein ubiquitination, a highly regulated cellular process controlled in part by DUBs to maintain protein homeostasis with appropriate protein levels and function, contributes to a large number of wide-ranging human diseases when aberrantly dysregulated. DUBs, as members of diverse protein complexes, are key regulators of ubiquitin recycling, processing, proofreading and disassembly. DUBs contain a catalytic domain surrounded by one or more accessory domains, some of which contribute to target recognition, and collectively represent molecular features ideally suited for therapeutic intervention.

"DUBs continue to prove to be highly attractive drug discovery targets warranting further exploration," stated Steven Tregay, Ph.D., President and CEO, FORMA Therapeutics. "A tremendous impact has been made by organizing diverse scientific disciplines within a consortia framework to advance protein homeostasis research and discoveries into active research. Additionally, this partnership’s discovery programs, by virtue of structural and computational insights, have already helped accelerate new advances in medicinal chemistry."

These virtual companies represent the collective efforts of a collaborative consortium consisting of FORMA, CRT-DL and five Cancer Research UK scientists including:

Professor Michael Clague – University of Liverpool, Liverpool, UK
Dr. Benedikt Kessler – The University of Oxford, UK
Dr. David Komander – Medical Research Council, Laboratory of Molecular Biology, Cambridge, UK
Dr. Huib Ovaa – Chemical Biology Laboratory, Netherlands Cancer Institute, The Netherlands.
Professor Sylvie Urbé – University of Liverpool, Liverpool, UK

Keith Blundy, CEO of Cancer Research Technology, said, "The unique structure of this partnership unites complementary skills and capabilities to develop this very exiting emerging area of biology. The teams behind the newly formed virtual companies have proven expertise in translating research discoveries into potential new drugs – that may ultimately bring breakthrough cancer treatments to patients."

FORMA Therapeutics and CRT form two virtual companies to advance deubiquitination assets

On March 23, 2015 FORMA Therapeutics and Cancer Research Technology Ltd. (CRT) reported the formation of two new virtual Asset Discovery and Development Companies (ADDCos) with novel chemical matter targeting undisclosed deubiquitinating enzymes (DUBs) (Press release, Cancer Research Technology, MAR 23, 2015, View Source [SID1234523211]). ADDCos are virtual companies seeking to achieve rapid innovation in a compelling scientific area through the collaboration of academic thought leaders, FORMA drug discovery scientists and a world class development network.

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Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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This builds on an ongoing initiative between FORMA and CRT, the commercial arm of Cancer Research UK, to discover innovative tools, technologies and therapeutic drug candidates against a variety of DUBs that regulate protein homeostasis. Under their agreement, FORMA is pairing its ultra-efficient drug discovery capabilities with expertise from CRT’s Discovery Laboratories (CRT-DL) in translating academic discoveries and the exclusive world-class academic network of Cancer Research UK scientists.

Protein ubiquitination, a highly regulated cellular process controlled in part by DUBs to maintain protein homeostasis with appropriate protein levels and function, contributes to a large number of wide-ranging human diseases when aberrantly dysregulated. DUBs, as members of diverse protein complexes, are key regulators of ubiquitin recycling, processing, proofreading and disassembly. DUBs contain a catalytic domain surrounded by one or more accessory domains, some of which contribute to target recognition, and collectively represent molecular features ideally suited for therapeutic intervention.

"DUBs continue to prove to be highly attractive drug discovery targets warranting further exploration," stated Steven Tregay, Ph.D., President and CEO, FORMA Therapeutics. "A tremendous impact has been made by organizing diverse scientific disciplines within a consortia framework to advance protein homeostasis research and discoveries into active research. Additionally, this partnership’s discovery programs, by virtue of structural and computational insights, have already helped accelerate new advances in medicinal chemistry."

These virtual companies represent the collective efforts of a collaborative consortium consisting of FORMA, CRT-DL and five Cancer Research UK scientists including:

Professor Michael Clague – University of Liverpool, Liverpool, UK
Dr. Benedikt Kessler – The University of Oxford, UK
Dr. David Komander – Medical Research Council, Laboratory of Molecular Biology, Cambridge, UK
Dr. Huib Ovaa – Chemical Biology Laboratory, Netherlands Cancer Institute, The Netherlands
Professor Sylvie Urbé – University of Liverpool, Liverpool, UK
Keith Blundy, CEO of Cancer Research Technology, said: "The unique structure of this partnership unites complementary skills and capabilities to develop this very exiting emerging area of biology. The teams behind the newly formed virtual companies have proven expertise in translating research discoveries into potential new drugs – that may ultimately bring breakthrough cancer treatments to patients."

MEI Pharma Announces Top-Line Data From Randomized Phase II Clinical Study Of Pracinostat In Front-Line Myelodysplastic Syndrome

On March 23, 2015 MEI Pharma reported top-line data from a randomized Phase II clinical study of its investigational drug candidate Pracinostat in combination with azacitidine in patients with previously untreated intermediate-2 or high-risk myelodysplastic syndrome (MDS) (Press release, MEI Pharma, MAR 23, 2015, View Source [SID:1234502473]). The double-blind, placebo-controlled study enrolled a total of 102 patients, randomized one-to-one, at 19 sites in the U.S.

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According to the top-line data, the combination of Pracinostat and azacitidine showed no difference in the rate of complete remission (CR), the study’s primary endpoint, compared to azacitidine alone. Data from event-driven endpoints, including duration of response, event and progression free survival and overall survival, are immature and will require longer follow-up in order to achieve meaningful conclusions. There were no new or unexpected toxicities observed in the study. Fatigue, gastrointestinal toxicities and myelosuppresion occurred more frequently in the combination group and resulted in a higher rate of drug discontinuations compared to azacitidine alone. The Company expects to present full results of the study at a scientific meeting later this year.

"Our goal when we initiated this study was to build on prior data and rigorously assess the clinical benefit of Pracinostat in combination with azacitidine in MDS," said Daniel P. Gold, Ph.D., President and Chief Executive Officer of MEI Pharma. "While we are disappointed with these top-line response data, we are diligently analyzing the entire data set as well as subsets from this study. Specifically, we are trying to fully assess the impacts of discontinuations on clinically important efficacy outcomes, including duration of response, event and progression free survival and overall survival. These findings will be important to inform the future development path for Pracinostat."

At the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting In December 2014, the company reported significant clinical activity from 33 evaluable patients in an open-label, single-arm Phase II study of Pracinostat and azacitidine in elderly patients with newly diagnosed acute myeloid leukemia (AML). Further follow-up indicates that the response rate and overall survival of these patients continued to increase. To date, 12 patients have been on study for more than six months, including five who have surpassed one year. Data from all 50 patients enrolled in this study have been submitted for presentation at the European Hematology Association (EHA) (Free EHA Whitepaper) Annual Congress in June 2015.

"AML represents another important component of our Pracinostat development strategy," continued Dr. Gold. "We remain encouraged by the durable responses and long-term tolerability observed in our ongoing Phase II study and will continue to monitor these patients closely to get a better estimate of the survival benefit. However, we do not intend to initiate any further studies of Pracinostat and azacitidine until we have gained a more complete understanding of the totality of clinical data surrounding the combination. We expect to be in a position to share more information regarding these findings and future development plans for Pracinostat later this year."

About Pracinostat

Pracinostat is an oral histone deacetylase (HDAC) inhibitor that has been tested in a number of Phase I and Phase II clinical studies in advanced hematologic disorders and solid tumor indications. Pracinostat has been generally well tolerated in more than 300 patients, with manageable side effects often associated with drugs of this class, notably fatigue. Pracinostat has exhibited pharmacokinetic properties in these studies that compare favorably to other oral HDAC inhibitors, including Zolinza (vorinostat) and Farydak (panobinostat).

MEI Pharma owns exclusive worldwide rights to Pracinostat.