Epizyme's PRMT5 inhibitor shows efficacy in pre-clinical models of mantle cell lymphoma

Dec 10 2014

Epizyme, Inc. (NASDAQ:EPZM), a clinical stage biopharmaceutical company creating innovative personalized therapeutics for patients with genetically defined cancers, announced today the results from a preclinical study showing in vitro and in vivo activity of its first-in-class PRMT5 inhibitor EPZ015666 in mantle cell lymphoma (MCL), an aggressive form of non-Hodgkin lymphoma (NHL). PRMT5 is an arginine methyltransferase (RMT), a subset of histone methyltransferases (HMTs), that is overexpressed in multiple human malignancies, including MCL. These data will be presented today by Elayne Penebre, Ph.D., Senior Scientist, Epizyme, at the 56^th annual meeting of the American Society of Hematology (ASH) in San Francisco, Calif.

“PRMT5 is the third target to come from the Epizyme platform, following EZH2 and DOT1L. Not only is EPZ015666 our first RMT inhibitor, it is the first RMTi to demonstrate in vivo activity in preclinical models. We look forward to extending our studies in MCL, as well as other tumor types,” said Robert A. Copeland, Ph.D., Chief Scientific Officer, Epizyme.

EPZ015666 demonstrated potent killing of cancer cells in vitro and efficacy in animal models of MCL, with correlation to methyl mark inhibition. EPZ01566 is orally bioavailable and demonstrated dose-dependent inhibition of intracellular symmetric arginine di-methylation of SmD3, a PRMT5 substrate that plays a critical role in RNA processing. In pre-clinical studies, Z138 and Maver MCL cell lines were shown to be sensitive to EPZ015666, and in xenografts of these cell lines, the compound showed dose-dependent tumor growth inhibition.

The PRMT5 clinical development program is part of a collaboration and license agreement with GSK.