ORIC selects rinzimetostat Phase 3 dose and expects Himalayas-1 start in 1H 2026

ORIC Pharmaceuticals reported first quarter 2026 financial results and operational updates, including selection of rinzimetostat 400 mg once daily as the Recommended Phase 3 Dose in combination with darolutamide for the Himalayas-1 Phase 3 global registrational trial in post-abiraterone mCRPC. The company said the trial is expected to initiate in 1H 2026, and reported rinzimetostat data in post-abiraterone mCRPC supporting a potential best-in-disease profile, including a highly differentiated safety profile and landmark rPFS consistent with a competitor PRC2 inhibitor.

As of the March 2026 presentation cutoff dates, rinzimetostat 400 mg once daily in combination with darolutamide demonstrated compelling safety and efficacy across multiple endpoints in post-abiraterone mCRPC. The vast majority of treatment-related adverse events were Grade 1 in severity and consistent with PRC2 and androgen receptor inhibition. A single Grade 3 treatment-related adverse event was observed, and no Grade 4 or 5 adverse events were attributed to rinzimetostat or darolutamide. Dose modifications were rare, with one interruption and one discontinuation, and no dose reductions were required.

With a median follow up of 4.9 months, landmark rPFS rates were 93%, 84%, and 84% at 3, 4, and 5 months, respectively. The company said these rates are consistent with the competitor PRC2 inhibitor currently in Phase 3 in post-abiraterone mCRPC patients and superior to available standard-of-care therapies, including Xtandi, Jevtana, Taxotere, and Pluvicto; for reference, the 5-month landmark rPFS for these approved therapies ranges from approximately 60% to 75%. In the same cohort, 47% of patients, or 7 of 15, achieved a PSA50 response, with 33%, or 5 of 15, confirmed, and 71% of patients, or 10 of 14, achieved more than 50% ctDNA reduction.

ORIC also reported early rinzimetostat dose optimization data in patients with mCRPC previously treated with AR inhibitors. Rinzimetostat 400 mg once daily in combination with the AR inhibitor darolutamide demonstrated landmark rPFS rates of 93%, 85%, and 85% at 3, 4, and 5 months, respectively, with a median follow-up of 4.8 months. The company said it anticipates a rinzimetostat program update in 2H 2026.

In earlier discussion of development plans, the company said rinzimetostat Phase 3 was planned to start after a dose-optimization early look in 20 to 25 patients reporting PSA50 and PSA90 and a 3- to 4-month landmark analysis rather than a mature PFS readout. The company had said it had not seen meaningful differences between apalutamide and darolutamide combinations in safety or efficacy to date, and that the choice for the first Phase 3 was likely to come down to strategic considerations.

For enozertinib, the company said it completed enrollment in the Phase 1b trial as a single agent in first-line patients with advanced NSCLC harboring EGFR exon 20 insertion mutations, and continues to enroll a Phase 1b single-agent trial in first-line patients with advanced NSCLC harboring EGFR atypical mutations and a Phase 1b trial in combination with subcutaneous amivantamab in first-line patients with advanced NSCLC harboring EGFR exon 20 insertion mutations. The company had previously said enozertinib showed a 100% CNS response in a small first-line cohort and that it expected three 20-25 patient readouts in 2H25, with potential Phase 3 starts thereafter.

ORIC said cash and investments of approximately $420 million are expected to provide runway into 2H 2028 and beyond anticipated primary endpoint readout from the first Phase 3 trial for rinzimetostat. In earlier remarks on funding, the company said it had raised $244 million and that its runway assumption was fully burdened, including funding a Phase 3 study for rinzimetostat and starting a Phase 3 study for enozertinib, though dependent on securing a clinical supply agreement for the androgen receptor inhibitor partner.