Oric Pharmaceuticals (ORIC) 3rd Annual Guggenheim Healthcare Innovation Conference summary

Pipeline overview

• Two late-stage oncology programs: rinzimetostat, an allosteric PRC2 inhibitor, and enozertinib, an EGFR TKI targeting atypical mutations and exon 20 insertions.

Rinzimetostat in prostate cancer

• Rinzimetostat binds the EED pocket of PRC2; preclinical work indicates similar signaling effects and potency to catalytic EZH2 inhibitors, with improved solubility, potency and bioavailability.

• Recommended Phase III dose is 400 mg once daily; half-life is 24 hours. A sustained PK profile may support better tolerability than short-half-life, frequently dosed mevrometostat, based on data to date.

• Rinzimetostat is paired with darolutamide; enzalutamide and apalutamide are CYP inducers and can affect drug exposure. Early data show less inter-patient variability and a favorable safety profile, which remains subject to maturation.

• Pfizer's MEVPRO-1 readout shifted to February 2027. Prior randomized Phase II data showed ~14 months for mevrometostat plus enzalutamide versus 6 months for enzalutamide alone; a positive Phase III result would further validate the PRC2-plus-AR inhibitor approach.

• Himalayas-1 began in 2026, enrolling ~600 post-abiraterone metastatic CRPC patients; each control option, an AR inhibitor or docetaxel, is capped at 60%. Enrollment is expected to take ~16 months, with topline data in H1 2028.

• A potential second Phase III study is under evaluation for post-AR inhibitor metastatic CRPC or metastatic CSPC; CSPC offers a larger population and potential treatment duration of ~5 years. A 2H 2026 program update may cover trial enrollment, study selection or incremental data.

Enozertinib in EGFR-mutant lung cancer

• At the recommended Phase III dose in first-line atypical EGFR mutations, response rate was 80%, or 84% by investigator assessment; CNS ORR was 70% by investigator and close to 70% by RANO criteria.

• Baseline brain metastases affected 65% of patients; most were untreated. The study reported 0% treatment discontinuation and very low Grade 3 adverse-event rates.

• Redwood-1 is planned for H1 2027: randomized enozertinib 80 mg once daily versus physician's choice of osimertinib or afatinib, including PACC and classical-like mutations and patients with or without active brain metastases.

• Redwood-1 may allow an interim ORR and DOR analysis for potential accelerated approval, followed by a PFS primary endpoint. Afatinib is the only approved atypical-mutation option, while osimertinib is guideline-recommended; the control split may favor afatinib.

• Exon 20 development spans monotherapy, chemotherapy combination and amivantamab combination, with clinical supply secured from J&J. An update is expected mid-2027; results across response, CNS activity and tolerability will inform whether to advance to Phase III.