Oric Plans H1 2026 Phase 3 Rinzimetostat Start and 80 mg Enosertinib Phase 2 Dose
Oric plans to start its first Phase 3 rinzimetostat trial in H1 2026 after dose optimization in 20 to 25 mCRPC patients demonstrating a 20–24 hour half-life and dual EZH2/EZH1 inhibition. Its enosertinib asset, showing 100% response in EGFR exon 20 and PAK-mutant brain metastases, adopts an 80 mg Phase 2 dose.
1. Rinzimetostat Program Details
Oric’s allosteric PRC2 inhibitor rinzimetostat targets the EED binding site to inhibit both EZH2 and EZH1, with clinical pharmacokinetics demonstrating a 20–24 hour half-life versus just hours for competitor inhibitors. After completing dose exploration in metastatic castration-resistant prostate cancer combinations with apalutamide and darolutamide, Oric advanced into dose optimization in approximately 20 to 25 patients and plans to initiate its first Phase 3 study in the first half of 2026.
2. Enosertinib Differentiation
Enosertinib, an EGFR inhibitor active against exon 20 alterations and PAK mutations, has shown 100% overall responses in small first-line cohorts including untreated brain metastases, underscoring its CNS penetrance. Broad dose exploration across more than 170 patients identified 80 mg as the recommended Phase 2 dose based on optimal efficacy and lower discontinuation rates compared with higher doses.
3. 2026 Clinical Catalyst Timeline
Oric outlined three key milestones for 2026: a Q1 update with PSA50/PSA90 response rates, safety, tolerability, ctDNA and early durability data from dose optimization, initiation of the first rinzimetostat Phase 3 study in H1, and a program update in H2 with further clinical and biomarker insights.