On April 2, 2014 GlaxoSmithKline announced its decision to stop the MAGRIT trial (NCT00480025), a Phase III trial of its MAGE-A3 cancer immunotherapeutic in non-small cell lung cancer (NSCLC) patients, after establishing that it will not be possible to identify a sub-population of gene-signature positive NSCLC patients that may benefit from the treatment (Press release GlaxoSmithKline, APR 2, 2014, View Source [SID:1234500361]).
Data from the trial announced on 20 March 2014 showed that it did not meet its first or second co-primary endpoints as it did not significantly extend disease-free survival (DFSiv) when compared to placebo in either the overall MAGE-A3 positive population (first co-primary endpoint) or in those MAGE-A3-positive patients who did not receive chemotherapy (second co-primary endpoint).
GSK continued with the MAGRIT trial to investigate the third co-primary endpoint of DFS in a gene signature positive sub-population, which was designed to identify a subset of MAGE-A3 positive patients that may benefit from the treatment. However, the pre-planned independent third-party analysis of a proportion of the data (to identify a gene signature classifier) has concluded that assessment of the third co-primary endpoint is not feasible due to an insufficient treatment effect.
The trial will be stopped and GSK will now gain access to the un-blinded data, in order to conduct a full assessment of the findings and understand learnings for other aspects of immunotherapy development within GSK.
The Independent Data Monitoring Committee (IDMC) indicated that its review of the current safety information revealed no specific safety concern and the data is in line with the known safety information for the MAGE-A3 cancer immunotherapeutic.
MAGRIT, a randomised, double-blind, placebo-controlled trial, evaluated the efficacy and safety of the MAGE-A3 cancer immunotherapeutic in Stage IB, II and IIIA completely resected non-small cell lung cancer (NSCLC) patients whose tumours expressed the MAGE-A3 gene.
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Novel Pharmacodynamic Assays to Measure Glutaminase Inhibition Following Oral Administration of CB-839 (Parlati, et al.)
On April 1, 2014 Calithera Biosciences presented the corporate presentation (Presentation, Calithera Biosciences, APR 1, 2014, View Source [SID1234535308]).
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NEOMED includes a new drug discovery project in its pipeline
On April 1, 2014 NEOMED, an organization whose mission is to create a bridge between academic research and the pharmaceutical industry, reported the launch of a new oncology drug discovery project (Press release, NEOMED, APR 1, 2014, View Source [SID1234527383]). The project, from a US company Epigenetix Inc. (Florida), has been selected by NEOMED to develop novel inhibitors of Brd4, a protein that functions as an epigenetic modulator and whose potential in the treatment of cancer is being explored. The initial stages of drug discovery will involve IntelliSynRD, a Montreal-based medicinal chemistry company located in the NEOMED Institute.
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"This is a very important project for NEOMED which we will undertake in collaboration with our partners. We aim to deliver a candidate drug within the next six to eight months. We are confident that we can achieve this together thanks to our team of scientists and the support of our network at the NEOMED Institute, and elsewhere in Canada." said Dr. Max Fehlmann, President and Chief Executive Officer of NEOMED and the NEOMED Institute.
"We are very pleased to have the support of an organization such as NEOMED to advance the development of new inhibitors of Brd4 and confirm the importance of epigenetics in the treatment of various forms of cancer. NEOMED’s expertise and its network will quickly move this project forward. The fact that our preferred provider of medicinal chemistry, IntelliSynRD, is part of the NEOMED Institute is an important advantage for the success of the project," said Joe Collard, President and Chief Executive Officer of Epigenetix Inc.
The most recent discoveries have shown that changes in the spatial shape of DNA can be as important as those in its sequence to explain the causes of certain diseases, in particular cancers. Although the DNA sequence cannot be easily modified, the spatial form of the DNA molecule is controlled by a family of enzymes that can be targeted with new classes of drugs. The ambition of epigenetics approaches is to restore the normal functions, especially in cancer cells.
Fairjourney Biologics, BioRap Technologies and Hadasit Medical Research Services and Development Ltd. collaborate to discover therapeutic antibodies that modulate Heparanase, a validated target for cancer therapy
On April 1, 2014 BioRap Technologies reported that Fairjourney Biologics signed a Research and Option Agreement with BioRap Technologies at the Rappaport Institute and Hadasit Medical Research Services and Development Ltd. to develop antibodies against Heparanase (Press release, BioRap Technologies, APR 1, 2014, View Source [SID1234516033]). Heparanase was discovered as a target for anti-cancer therapy by Prof. Israel Vlodavsky, a cancer research scientist at the Rappaport Institute and Hadassah Medical Center (Nat. Med. 1999. 5: 793-802).
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Under the terms of the agreement, Fairjourney Biologics will use its expertise in antibody discovery and engineering to develop a superior panel of antibodies, using phage display to tackle multiple epitopes of this target. BioRap Technologies will perform the in-vitro and in-vivo proof of concept at the Rappaport Institute. Fairjourney Biologics has an option to develop the antibody drug candidates on an exclusive basis.
Vlodavsky’s discovery of the extracellular matrix as a reservoir for bioactive molecules provided the basis for the current appreciation of the tumor microenvironment and its significance in cancer progression and treatment. A major achievement of Vlodavsky is the cloning and characterization of heparanase (endo-β-D-glucuronidase), the sole functional enzyme responsible for degradation and remodeling of the extracellular matrix. The normal physiological functions of Heparanase include tissue remodeling and repair.
Abnormal expression of Heparanase is implicated in a variety of pathologic processes, including tumor growth, angiogenesis, metastasis, inflammation and glomerular diseases. Preferential expression of this enzyme has been shown in various human tumors. Heparanase knock-out mice have been reported to lack significant abnormalities. Vlodavsky is the pioneering scientist in this area of research, offering basic insights and new treatment strategies for various cancers and other diseases.
Currently, various chemically modified heparins or heparan sulfate mimics have been generated as Heparanase inhibitors. PI-88 (sulfated malto-oligosaccharide), PG545 (fully sulfated tetrasaccaride), Roneparstat (SST0001), and M402 (both glycol-split species of heparin) are being tested in Phase I/II clinical trials (hepatocellular carcinoma, melanoma, myeloma, lung carcinoma, pancreatic carcinoma).
"The biology of Heparanase makes this enzyme a very attractive novel therapeutic target. We are delighted with the opportunity to generate neutralizing antibodies that are expected to profoundly affect tumor growth, angiogenesis and metastasis," commented Maria Gonzalez-Pajuelo, Fairjourney Biologics’ CSO.
António Parada, Fairjourney Biologics’ CEO emphasized, "After an outstanding track record developing new therapeutic antibodies to partners, it’s time for the company to also have assets. This move will foster value creation and secure broader services from our clients, by demonstrating our capability to deliver more comprehensively on the value chain."
Israel Vlodavsky received his Ph.D. from the Wiezmann Institute (Rehovot, Israel) followed by a postdoctoral training in UCLA and UCSF. He then established the Tumor Biology Research unit of the Hadassah-Hebrew University Medical Center. In 2002, he was recruited to the Technion (Haifa, Israel) where he established the Cancer & Vascular Biology Research Center View Source
FORMA THERAPEUTICS AND CELGENE CORPORATION ANNOUNCE A NOVEL AND EXPANSIVE MULTI-YEAR STRATEGIC ALLIANCE
On April 1, 2014 FORMA Therapeutics, an innovative R&D organization in pursuit of ground-breaking medicines in oncology and other therapeutic areas, reported a second strategic collaboration and option agreement with Celgene Corporation, a leader in addressing high unmet medical needs (Press release, Forma Therapeutics, APR 1, 2014, View Source [SID:1234509320]).
"It is extremely rewarding to have our team recognized for their creativity and productivity and to receive substantial funding. Most of all, we look forward to expanding our relationship with Celgene, which is based on a deep and open scientific interchange."
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This new collaboration will enable FORMA to extend its unique capabilities across broad areas of chemistry and biology. Upon signing the agreement, FORMA received an upfront cash payment of $225 million, and the parties entered into a collaboration with a term of 3 ½ years. In addition to the 3 ½ year collaboration, Celgene has the option to enter into up to two additional collaborations with terms of two years each for additional payments totaling approximately $375 million. Should each collaboration be successful and Celgene ultimately elect to enter all three collaborations, the combined duration of the three collaborations may extend for at least 7 ½ years. During the third collaboration term, Celgene will have the exclusive option to acquire FORMA, including the U.S. rights to all licensed programs, and worldwide rights to other wholly owned programs within FORMA at that time.
"This new alliance enables FORMA to maintain autonomy in defining our research strategy and conducting discovery through early clinical development of our product portfolio."
The scope and potential duration of this collaboration allows the parties to comprehensively evaluate emerging target families for which FORMA’s platform has exceptional strength. Under the terms of the agreement, Celgene has an option to license the rights to select current and future FORMA programs in exchange for undisclosed additional development and regulatory milestone payments. Celgene will assume responsibility for all global development activities and costs after completion of Phase 1 clinical trials. FORMA retains U.S. rights to all such licensed assets, including responsibility for manufacturing and commercialization. For products not licensed to Celgene, FORMA will maintain worldwide rights.
"Progress in our existing collaboration, coupled with emerging evidence of the power of FORMA’s platform to generate unique chemical matter across important emerging target families, leads us to expand the collaboration and enable a unique collaborative relationship — one that complements the significant strengths of our internal discovery and development organization," said Thomas Daniel, M.D., President, Global Research and Early Development, Celgene Corporation.
"Independent from the previously signed partnership with Celgene whereby they secured ex-U.S. rights to a defined set of protein homeostasis targets, this second agreement expands across FORMA’s preclinical and future clinical development efforts, encompassing numerous protein target families and covering a broad range of therapeutic areas," said Steven Tregay, Ph.D., President and CEO, FORMA Therapeutics. "Importantly, this new alliance enables FORMA to maintain autonomy in defining our research strategy and conducting discovery through early clinical development of our product portfolio. It aligns our company with Celgene’s global leadership in hematology and immune-mediated inflammatory diseases and a shared strategic directive to transform healthcare."
Kenneth W. Bair, Ph.D., Chief Scientific Officer and Head of Research and Development, FORMA Therapeutics, added, "It is extremely rewarding to have our team recognized for their creativity and productivity and to receive substantial funding. Most of all, we look forward to expanding our relationship with Celgene, which is based on a deep and open scientific interchange."
"This second collaboration with FORMA is based upon a very strategic relationship and complete alignment between FORMA’s and Celgene’s R&D efforts. This expansive collaboration will allow FORMA’s powerful drug discovery engine to probe multiple emerging areas of biology in the pursuit of step-ahead therapies for future patients," stated George Golumbeski, Ph.D., Senior Vice President for Business Development, Celgene Corporation. "Both organizations take pride in developing creative alliances that fully enable the science to succeed, and this initiative is truly reflective of that concept."
"The expansion of FORMA’s relationship with Celgene demonstrates a mutual belief in the potential of FORMA’s drug discovery programs to provide meaningful clinical outcomes for patients across a broad variety of diseases," noted Rob Sarisky, Ph.D., Chief Business Officer, FORMA Therapeutics. "This substantial collaboration affords us an opportunity to rapidly accelerate FORMA’s innovations to clinical proof of relevance within our capital-efficient business structure."