Preclinical data details effects of EZH2 inhibitor
CAMBRIDGE, Mass.—Epizyme, Inc. has published data from preclinical studies of its clinical candidate EPZ-6438, which is being explored as a potent, selective small-molecule inhibitor of histone methyltransferase EZH2 in genetically defined non-Hodgkin lymphoma (NHL). The research appeared in the April issue of Molecular Cancer Therapeutics. The compound is capable of soliciting sustained tumor growth inhibition in animal models of EZH2 mutant-bearing NHL, and the work also enabled the team to develop an assay to determine methylation of H3K27 in tumor, bone marrow, peripheral blood mononuclear cells and other surrogate tissues, as well as a quantitative PK/PD relationship. The data also details the correlation between inhibition of EZH2, methylation of the EZH2 target, reversal of lymphomagenic gene expression and anti-proliferative effects specific to EZH2 mutant-bearing NHL cell lines.