Oric Pharmaceuticals (NASDAQ:ORIC) used a fireside chat at the Guggenheim Biotech Conference to outline development priorities for its two lead oncology programs and to reiterate its expected 2025 milestones, including plans to initiate a Phase 3 study in prostate cancer in the first half of the year.
Company focus and lead programs
Chief Business Officer Matt Panuwat described ORIC as a clinical-stage oncology company focused on overcoming resistance in cancer using small-molecule therapies, with emphasis in prostate, lung, and breast cancer. He highlighted two lead assets:
- Rinzimetostat (formerly ORIC-944), an allosteric PRC2 inhibitor being studied in prostate cancer in combination with Johnson & Johnson’s apalutamide and Bayer’s darolutamide.
- Enozertinib (formerly ORIC-114), a selective, brain-penetrant EGFR inhibitor targeting EGFR exon 20 and PACC mutations in lung cancer.
Rinzimetostat: rationale for moving toward Phase 3
In discussing the PRC2 inhibitor landscape, ORIC executives referenced Pfizer’s PRC2 program mevrometostat and noted that the timing of Pfizer’s Phase 3 results is uncertain. Panuwat said Pfizer indicated at the JPMorgan conference that data would come in 2026, while analyst expectations vary across the year.
Looking back to Pfizer’s randomized Phase 2 dataset presented at ASCO GU 2025 in post-abiraterone patients (80 total patients), Panuwat cited a progression-free survival (PFS) of 14.3 months for mevrometostat plus enzalutamide versus 6.2 months for enzalutamide alone. He also cited PSA response rates for Pfizer’s combination: PSA50 of 34% and PSA90 of 12%.
ORIC’s own 2025 dose escalation data for rinzimetostat showed what Panuwat characterized as early proof-of-concept, including a confirmed PSA50 of 40% and PSA90 of 20%. He cautioned that comparisons are cross-study and in small patient numbers, but said the Pfizer results helped “de-risk the mechanism” with a read-through to ORIC’s program.
On tolerability, Panuwat said ORIC has presented a more favorable safety profile so far, with “significantly less adverse events” in severity and frequency compared with what has been disclosed for Pfizer’s drug, which he said included Grade 3/4 gastrointestinal tolerability issues and hematologic toxicities.
What to expect from the Q1 dose optimization update
Panuwat said ORIC’s planned first-quarter update will include data from 20–25 patients and will represent one of two populations under study (post-abiraterone or post-androgen receptor inhibitor) and one of two combination partners (apalutamide or darolutamide). He said ORIC intends the Q1 update as an “early look” to inform the Phase 3 study it plans to start in the first half of the year, while also limiting disclosure for competitive reasons.
Metrics ORIC plans to show include PSA50 and PSA90 responses and safety/tolerability consistent with prior presentations. Panuwat emphasized that durability data will not represent a mature PFS readout; instead, ORIC expects to provide an early “landmark analysis” around three to four months, looking for evidence that patients are staying on therapy and that trends appear better than what would be expected from an androgen receptor inhibitor alone.
On selection of apalutamide versus darolutamide for Phase 3, ORIC said it has not seen meaningful differences between the two combinations in safety or efficacy to date. Executives noted trade-offs between the agents, including that darolutamide is not a CYP inducer (reducing certain drug-drug interaction concerns), while apalutamide is once daily (versus twice daily with food for darolutamide). They said the choice for the first Phase 3 is likely to come down to strategic considerations, and that ORIC does not view that choice as binding for future Phase 3 trials.
Funding position and runway
CFO Dominic Piscitelli said ORIC raised $244 million in the middle of the prior year to ensure sufficient runway and to avoid being dependent on market conditions or external readouts. He said the company’s cash runway extends into the second half of 2028.
Piscitelli said the runway assumption is “fully burdened” and includes ORIC funding a Phase 3 study for rinzimetostat and starting a Phase 3 study for enozertinib as well, including clinical and CMC costs. He added that the runway assumption does depend on securing a clinical supply agreement from either J&J or Bayer for the androgen receptor inhibitor used in the rinzimetostat Phase 3 combination.
Based on ORIC’s timing assumptions—starting rinzimetostat Phase 3 in the first half of this year—Piscitelli said the company could have data in the second half of 2027, and that runway extends beyond that expected readout.
Enozertinib: CNS activity focus and 2H data plan
Turning to enozertinib, Panuwat pointed to the company’s update at ESMO Asia and said systemic response rates in both first-line and previously treated settings for EGFR exon 20 and PACC mutations were competitive with, or slightly better than, reported competitor results. He emphasized what ORIC views as a key point of differentiation: central nervous system (CNS) activity.
Panuwat said that in first-line patients with measurable CNS disease in EGFR exon 20 and PACC cohorts, ORIC observed a 100% CNS response rate. He added that ORIC estimates about one-third of patients present with known CNS metastases at baseline and that roughly 50% may develop CNS metastases over the course of treatment, which the company views as a significant unmet need.
For the second half of the year, Panuwat said ORIC expects three readouts, each with 20–25 patients:
- First-line EGFR exon 20 monotherapy
- EGFR exon 20 in combination with amivantamab
- First-line EGFR PACC monotherapy
Across these cohorts, ORIC expects to report systemic response, CNS response, safety/tolerability, and durability. Executives also noted they expect competitor data in the first half of the year to help clarify benchmarks for differentiation.
On market sizing discussed during the session, ORIC estimated EGFR exon 20 mutations at roughly 2% of lung cancer (about 4,000–5,000 U.S. patients annually) and PACC mutations at at least 2.5% (about 5,000–6,000 U.S. patients annually). The company also described its combination strategy with amivantamab as a way to pair ORIC’s CNS activity with broader mutation coverage and potential resistance coverage, while acknowledging the need to monitor on-target toxicities such as rash and diarrhea when combining EGFR-directed agents.
About Oric Pharmaceuticals (NASDAQ:ORIC)
Oric Pharmaceuticals, Inc is a clinical-stage biopharmaceutical company headquartered in South San Francisco, California. The firm is dedicated to discovering and developing small molecule therapeutics designed to overcome resistance mechanisms in solid tumor oncology. Its research efforts focus on identifying novel targets and advancing precision medicines that can restore or enhance patient response when standard therapies fail.
The company’s pipeline features lead candidates such as ORIC-101, a selective, orally available antagonist of the glucocorticoid receptor currently being evaluated in Phase 1/2 trials for patients with solid tumors who have acquired resistance to chemotherapy and hormonal agents.
-logo-1200x675.png?v=20220915161652&h=45&w=95&zc=2){kind=logo}
