On March 25, 2025 ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, reported that a preclinical abstract highlighting the potential of ORIC-944, a potent and selective allosteric inhibitor of PRC2 to treat prostate cancer, has been accepted for poster presentation at the 2025 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting taking place April 25-30, 2025 in Chicago, IL (Press release, ORIC Pharmaceuticals, MAR 25, 2025, View Source [SID1234651410]).
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Poster presentation details:
Title: ORIC-944, a PRC2 inhibitor with best-in-class properties, restores luminal features and restricts adaptation in prostate cancer models, conferring synergy with AR pathway inhibitors
Abstract Number: 452
Date & Time: Sunday, April 27, 2025, 2:00 – 5:00 p.m. CT
Session Category: Experimental and Molecular Therapeutics
Session Title: Epigenetic Targets
Location: Poster Section 20
Abstract Highlights
ORIC-944 is a potent, highly selective, orally bioavailable, allosteric inhibitor of PRC2 that demonstrates best-in-class drug properties, including potency, solubility, and pharmacokinetics, with half-life supporting once daily dosing. In preclinical prostate cancer models, ORIC-944 demonstrated robust inhibition of PRC2, enhanced luminal cell state, and increased androgen receptor (AR) signaling. Analysis of chromatin revealed that ORIC-944 specifically restricts accessibility to lineage-associated transcription factors known to impart cellular plasticity in prostate cancer. This plasticity-restricted luminal state conferred by PRC2 inhibition is dependent on AR, leading to antitumor activity either in the hormone-depleted context or in the combination setting with an AR pathway inhibitor (ARPI). Together these data indicate that ORIC-944 reinforces a luminal cell state and, notably, restricts access to plasticity genes leading to a highly AR-dependent state in prostate models. This mechanism supports the observed preclinical synergy between PRC2 inhibition and ARPIs in both ARPI-sensitive and ARPI-resistant settings. These results position ORIC-944 as a potential best-in-class PRC2 inhibitor that blocks prostate tumor adaptation, restores luminal features, and sensitizes tumors to ARPIs. A phase 1b trial of ORIC-944 in combination with ARPIs is ongoing in metastatic prostate cancer (NCT05413421).