Dibs on DUBs
August 2013
by Jim Cirigliano  |  Email the author


LONDON—Cancer Research Technology (CRT)—a subsidiary of Cancer Research UK—and U.S.-based FORMA Therapeutics have announced a research collaboration designed to discover tools, technologies and drug candidates against a variety of protein homeostasis regulators called deubiquitinating enzymes (DUBs).  
Under the agreement, FORMA and CRT's Discovery Laboratories will broadly investigate various DUBs and will share responsibility for the drug discovery activities during the investigation's early stages, with FORMA leading on preclinical and early clinical development.  
In addition, a collaborative consortium will be formed consisting of FORMA and up to 10 of its Asset Discovery and Development Company subsidiaries, CRT's Discovery Laboratories and five principal investigators initially, including professors Michael Clague and Sylvie Urbé of the University of Liverpool, Dr. Benedikt Kessler of the University of Oxford, Dr. David Komander of the Medical Research Council at the Laboratory of Molecular Biology in Cambridge and Dr. Huib Ovaa of the Netherlands Cancer Institute's Chemical Biology Laboratory—all renowned academic researchers.
The partnership will combine FORMA's capacity for rapid screening and high-speed synthesis of targets, its compound library and its chemical biology approach with CRT's breadth of expertise and pre-established relationships with research partners and universities in the United Kingdom.  
Ubiquitin biology is a complex area that has been known for some time, but in which pharmaceutical interest has emerged only recently as its importance to a range of human diseases has become apparent. Ubiquitin-dependent pathways have been implicated in cancer, and FORMA began interrogating this space in September 2012. DUBs play a role in regulating protein ubiquitination, which is involved in many cellular processes. They can be used as tools for manipulating protein levels in cells.

"As key regulators of ubiquitin recycling, processing, proofreading and disassembly, there is a tremendous opportunity to build a franchise of complementary therapeutics targeting the diverse collections of protein complexes," says Dr. Keith Blundy, CEO of CRT.  
Of approximately 90 known DUBs, about 50 have potential applications in oncology, although relatively little is known about this class of enzyme. Since announcing the collaboration, FORMA has already screened about a dozen targets and has triaged through the hits thus far.  
The partnership formed out of an existing relationship between the two organizations. "We met with FORMA back in 2010," says Blundy. "From this initial interaction involving compound sharing, we went on to discuss other ways of collaborating, and to build the DUBs alliance out of these discussions."  
"Our goal is quite broad," says FORMA Founder and CEO Dr. Steven Tregay. "We want to broadly survey the area of DUBs and bring some targets forward into clinical development. The area is fruitful—we hope to identify multiple clinical candidates."  
"This initiative with FORMA allows us and our Cancer Research UK investigators to explore a very exciting emerging area of cancer biology on an unprecedented scale and in a highly collaborative partnership that has the potential to deliver value for all parties and, most importantly, to bring new cancer drugs that will hopefully benefit patients in the future," says Blundy.  
FORMA Therapeutics is a Massachusetts-based drug discovery company that targets cancer pathways to create small-molecule cancer therapies. FORMA's goal is to build an integrated research and development organization that is able to operate on scale and move quickly into new areas of clinical interest. It is currently building a pipeline of cancer therapies in areas including tumor metabolism, epigenetics, protein homeostasis and protein-protein interactions.  
CRT is the for-profit arm and wholly owned subsidiary of Cancer Research UK, the world's largest cancer charity, based in London. CRT is a specialist commercialization and development company that works closely with international cancer scientists and their institutions to protect intellectual property and to establish links with commercial partners. CRT's Discovery Laboratories translate academic discoveries into industrial propositions. Discovery Laboratories has an active project portfolio of 15 projects and major partnerships with AstraZeneca and Cephalon.  
Code: E081322

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