Three partners, one target

Two British research organizations team with California-based pharma company to discover and develop novel blood cancer drug candidates

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DUBLIN, Calif.—Astex Pharmaceuticals Inc., a pharmaceuticalcompany dedicated to the discovery and development of novel small-moleculetherapeutics and based in a U.S. city with a name that evokes Ireland, hasinitiated a collaboration with two U.K.-based organizations, Cancer ResearchTechnology Ltd. (CRT) and The Institute of Cancer Research (ICR) in London.
Under the terms of the deal, the trio will work together todiscover and develop drug candidates targeting an undisclosed epigenetic targetin a blood cancer with high unmet medical need.
As the collaborators note, dysregulated epigeneticmechanisms are now understood to underlie various types of cancer, and thesemechanisms have been successfully targeted by the first generation ofepigenetic anticancer drugs. In some cases, they says, specific epigeneticmutational events can be linked to disease etiology, providing an opportunityto develop highly targeted personalized medicines and associated companiondiagnostics that will ultimately improve survival and reduce side effects.
The choice of Astex as a partner in this effort with CRT—thecancer-focused technology development and commercialization arm of CancerResearch UK—and ICR flows from that understanding, as Astex brings itsrespected fragment-based drug discovery platform and epigenetic drugdevelopment experience. At the same time, the collaboration enjoys ICR'sexpertise in blood cancer biology and proven success in drug discovery at theCancer Research UK Cancer Therapeutics Unit at the ICR.
"This new partnership builds on the highly successfulcollaboration which Astex entered into with the ICR and CRT in 2003 on anothercancer target, PKB/Akt," noted Dr. Harren Jhoti, president of AstexPharmaceuticals, in the news release about the collaboration. "Thatcollaboration led to the discovery of two clinical candidates, the first ofwhich, AZD5363, was taken into Phase I by our partner AstraZeneca in early 2011and the second of which, AT13148, is being prepared to be taken into Phase Iunder our development partnership with Cancer Research UK."
Discussions on the current collaboration began about a yearago when Astex and ICR scientists began to discuss their interests andexpertise in epigenetics and their respective drug discovery efforts focusingon a novel epigenetics target, according to Tom Heightman, director ofmedicinal chemistry at Astex and project leader for the collaboration.
"Although this collaboration did not flow directly fromAstex's past collaboration with ICR and CRT on PKB, given that our PKBcollaboration (partly funded by Cancer Research UK) led to the discovery of twonew drugs which are continuing to move forward in development, we still havevery regular contact with scientists from ICR and Cancer Research UK,"Heightman tells ddn. "Our frequentcontact and our experiences of working together very successfully in the pastwere certainly factors in triggering our interest and discussions about thisnew collaboration."
As Prof. Paul Workman, director of the Cancer Research UKCancer Therapeutics Unit at ICR puts it, "ICR scientists are pioneers atunraveling blood cancer drug targets, which others have considered challengingto drug effectively. We have a very strong track record of designing drugs toattack challenging biological targets and bringing them into clinical trial,and given Astex's complementary expertise, we are very excited about thepotential of this collaboration."
Heightman says that Astex recognizes the strategic value ofestablishing alliances with leading academic institutes that can providecomplementary expertise and capabilities, particularly in target identificationand validation to support its drug discovery projects to identify noveltargeted agents. 
"Epigenetics is an exciting new field in cancer therapy," henotes. "The timing of this specific effort is driven by two recent scientificadvances—first, elucidation of the roles of a number of epigenetic regulatoryproteins in specific groups of cancer patients, providing both a strongtherapeutic rationale and clear diagnostic prediction of patient responses; andsecond, demonstration of the tractability of new epigenetic regulatory proteinfamilies for small-molecule discovery."
The collaboration fits well with Astex's desire to build onits epigenetic franchise, with Heightman noting that Astex receives royaltiesfrom sales of Dacogen, which was developed by one of its founder companiesSupergen—but it also fits well with ICR's goal to continue to developcutting-edge personalized medicines for patients with inadequately treatedcancers, he adds.
"The deal will ensure that the research program benefitsfrom the necessary investment to progress the research to its full potentialwhile building on the validation and assay development work that has beencarried out at the ICR and funded by Cancer Research UK and others," said Dr.Phil L'Huillier, director of business management at CRT, in the announcementabout the deal.
In addition to its California headquarters, Astex has aEuropean corporate and research center in Cambridge, United Kingdom.

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