ORIC Pharmaceuticals Shares Positive Phase 1b Data For ORIC-944 in Combination With AR Inhibitors In mCRPC

ORIC Pharmaceuticals, Inc. has reported new efficacy and safety findings from its ongoing Phase 1b study evaluating ORIC-944, a potent PRC2 inhibitor, administered once daily in combination with approved androgen receptor (AR) inhibitors for patients with metastatic castration-resistant prostate cancer (mCRPC). The emerging data highlight the therapy’s potential to address mechanisms of resistance in heavily pretreated patients.

“We continue to be encouraged by ORIC-944 combination data, which further demonstrate its potential as a best-in-class PRC2 inhibitor that may benefit a broad range of patients with prostate cancer,” said Jacob M. Chacko, M.D., president and chief executive officer. “The tolerability and efficacy data to date provide compelling validation for the doses we’ve selected for the dose optimization portion of the Phase 1b trial. We look forward to sharing dose optimization data in 1Q 2026 ahead of initiating our first global Phase 3 registrational trial in mCRPC in the first half of next year.”

Participants in the study had previously received a median of three prior lines of treatment, including abiraterone acetate, at least one prior chemotherapy regimen, and various other approved or investigational agents. This median excludes background androgen deprivation therapy and first-generation AR inhibitors. In the dose-escalation cohorts, patients received ORIC-944 at 400 mg, 600 mg, 800 mg, or 1,200 mg once daily, paired with either apalutamide (240 mg once daily) or darolutamide (600 mg twice daily). Updated PSA data were available for 20 patients, while circulating tumor DNA (ctDNA) analyses were performed for 17 patients with detectable ctDNA at baseline. All results were assessed as of September 22, 2025.

The safety analysis indicates that ORIC-944 combined with apalutamide or darolutamide continues to be well tolerated, supporting long-term use. Most treatment-related adverse events (TRAEs) were Grade 1 or 2, consistent with the known biology of PRC2 and AR inhibition. As of the data cutoff, only one patient experienced a Grade 3 TRAE, and there were no Grade 4 or Grade 5 adverse events attributed to the combination therapy. These early results reinforce ORIC-944’s potential as a next-generation therapeutic option for resistant prostate cancer.