ORIC-944 + enzalutamide

ORIC-944 + enzalutamide is an investigational combination therapy currently studied for metastatic castration-resistant prostate cancer (mCRPC). ORIC-944 is a potent and selective allosteric inhibitor of the polycomb repressive complex 2 (PRC2) targeting the embryonic ectoderm development (EED) subunit, developed to counteract mechanisms of resistance to androgen receptor (AR) pathway inhibitors such as enzalutamide. Enzalutamide is a second-generation AR inhibitor used in the management of prostate cancer. Preclinical and early clinical studies show that ORIC-944 can render prostate cancer cells more sensitive to AR inhibition, and the combination demonstrates synergy by inducing luminal differentiation and suppressing tumor cell viability. The combination is under clinical evaluation, primarily for safety, tolerability, pharmacokinetics, and preliminary antitumor efficacy in mCRPC[3][5].