Dibs on DUBs

LONDON—Cancer Research Technology (CRT)—a subsidiary ofCancer Research UK—and U.S.-based FORMA Therapeutics have announced a researchcollaboration designed to discover tools, technologies and drug candidatesagainst a variety of protein homeostasis regulators called deubiquitinatingenzymes (DUBs).

Under the agreement, FORMA and CRT's Discovery Laboratorieswill broadly investigate various DUBs and will share responsibility for thedrug discovery activities during the investigation's early stages, with FORMAleading on preclinical and early clinical development.

In addition, a collaborative consortium will be formedconsisting of FORMA and up to 10 of its Asset Discovery and Development Companysubsidiaries, CRT's Discovery Laboratories and five principal investigatorsinitially, including professors Michael Clague and Sylvie Urbé of theUniversity of Liverpool, Dr. Benedikt Kessler of the University of Oxford, Dr.David Komander of the Medical Research Council at the Laboratory of MolecularBiology in Cambridge and Dr. Huib Ovaa of the Netherlands Cancer Institute'sChemical Biology Laboratory—all renowned academic researchers.

The partnership will combine FORMA's capacity for rapidscreening and high-speed synthesis of targets, its compound library and itschemical biology approach with CRT's breadth of expertise and pre-establishedrelationships with research partners and universities in the United Kingdom.

Ubiquitin biology is a complex area that has been known forsome time, but in which pharmaceutical interest has emerged only recently asits importance to a range of human diseases has become apparent.Ubiquitin-dependent pathways have been implicated in cancer, and FORMA beganinterrogating this space in September 2012. DUBs play a role in regulatingprotein ubiquitination, which is involved in many cellular processes. They canbe used as tools for manipulating protein levels in cells.

"As key regulators of ubiquitin recycling, processing, proofreadingand disassembly, there is a tremendous opportunity to build a franchise ofcomplementary therapeutics targeting the diverse collections of proteincomplexes," says Dr. Keith Blundy, CEO of CRT.

Of approximately 90 known DUBs, about 50 have potentialapplications in oncology, although relatively little is known about this classof enzyme. Since announcing the collaboration, FORMA has already screened abouta dozen targets and has triaged through the hits thus far.

The partnership formed out of an existing relationshipbetween the two organizations.

"We met with FORMA back in 2010," says Blundy. "From thisinitial interaction involving compound sharing, we went on to discuss otherways of collaborating, and to build the DUBs alliance out of thesediscussions."

"Our goal is quite broad," says FORMA Founder and CEO Dr.Steven Tregay. "We want to broadly survey the area of DUBs and bring sometargets forward into clinical development. The area is fruitful—we hope toidentify multiple clinical candidates."

"This initiative with FORMA allows us and our CancerResearch UK investigators to explore a very exciting emerging area of cancerbiology on an unprecedented scale and in a highly collaborative partnershipthat 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 discoverycompany that targets cancer pathways to create small-molecule cancer therapies.FORMA's goal is to build an integrated research and development organizationthat is able to operate on scale and move quickly into new areas of clinicalinterest. It is currently building a pipeline of cancer therapies in areasincluding tumor metabolism, epigenetics, protein homeostasis andprotein-protein interactions.

CRT is the for-profit arm and wholly owned subsidiary ofCancer Research UK, the world's largest cancer charity, based in London. CRT isa specialist commercialization and development company that works closely withinternational cancer scientists and their institutions to protect intellectualproperty and to establish links with commercial partners. CRT's DiscoveryLaboratories translate academic discoveries into industrial propositions.Discovery Laboratories has an active project portfolio of 15 projects and majorpartnerships with AstraZeneca and Cephalon.