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Rinzimetostat 400 mg once daily selected as RP3D in combination with darolutamide for Himalayas-1 global Phase 3 registrational trial in post-abiraterone mCRPC, with initiation expected in 1H 2026
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At a median follow-up of ~5 months, landmark 5-month rPFS of 84% is consistent with competitor PRC2 inhibitor and substantially better than standard of care therapies in mCRPC
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Highly differentiated, potential best-in-disease safety profile, with significantly lower frequency and severity of adverse events, nearly all Grade 1 or 2, and far fewer treatment modifications than competitor regimens
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Company to host a conference call and webcast today at 4:30 pm ET
SOUTH SAN FRANCISCO, Calif. and SAN DIEGO, March 31, 2026 (GLOBE NEWSWIRE) -- ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, today announced a rinzimetostat (ORIC-944) program update and potential best-in-disease efficacy and safety data from the Phase 1b trial of once daily rinzimetostat in combination with darolutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) who were previously treated with abiraterone acetate (abiraterone).
“The combination dose optimization data announced today provide confirmatory evidence that support rinzimetostat’s potential best-in-disease clinical profile, reinforcing its path towards becoming a practice-changing therapy for patients with prostate cancer,” said Jacob M. Chacko, M.D., president and chief executive officer. “The durability observed to date is consistent with the competitor PRC2 inhibitor currently in Phase 3 in mCRPC and appears meaningfully improved relative to other approved standard of care therapies. Notably, rinzimetostat demonstrated this impressive durability with a markedly cleaner safety profile than competitor regimens.”
“These data provide compelling validation for advancing rinzimetostat in combination with darolutamide into Phase 3 registrational trials in patients with prostate cancer,” said Pratik S. Multani, M.D., chief medical officer. “We expect our first Phase 3 trial, Himalayas-1, in patients with mCRPC previously treated with abiraterone, to initiate in the first half of 2026 while we continue to evaluate rinzimetostat in additional indications in prostate cancer and beyond.”
Rinzimetostat Phase 1b Dose Optimization Data in Combination with Darolutamide
Patients were previously treated with a median of two prior lines of therapy, including abiraterone, up to one prior line of chemotherapy, and a variety of other approved and investigational treatment regimens. This median excludes background androgen deprivation therapy or first-generation androgen receptor (AR) inhibitors that the patients may have received. 18 patients were treated with 400 mg of rinzimetostat once daily and 15 patients were treated with 600 mg of rinzimetostat once daily, both in combination with the standard dose of darolutamide at 600 mg twice daily.
Rationale for Selection of the Recommended Phase 3 Dose (RP3D)
At the 400 mg dose, rinzimetostat in combination with darolutamide continues to be well tolerated and demonstrates a safety profile supportive of long-term administration and sustained patient adherence. As of the January 16, 2026 data cutoff, the vast majority of treatment-related adverse events (TRAEs) were Grade 1 in severity and consistent with PRC2 and AR inhibition. The most common TRAEs were fatigue (39%; 17% Grade 1 and 22% Grade 2), diarrhea (22%; 17% Grade 1 and 6% Grade 2) and nausea (22%; all Grade 1). A single Grade 3 TRAE was observed, and no Grade 4 or 5 AEs were attributed to rinzimetostat or darolutamide. Dose modifications were rare (one interruption and one discontinuation), with no dose reductions required. The 600 mg dose of rinzimetostat in combination with darolutamide was associated with a modestly higher rate of adverse events and dose modifications. In a broader dataset of post-ARPI (androgen receptor pathway inhibitor) patients (n=72, inclusive of the post-abiraterone patients), the safety and tolerability profile was consistent with the post-abiraterone cohort.
To support the selection of the recommended Phase 3 dose in accordance with the FDA's Project Optimus initiative, the company conducted a comprehensive exposure-response (E-R) analysis in over 100 patients across both the single-agent and combination data evaluating the relationship between rinzimetostat drug exposure versus efficacy and safety outcomes. The analysis demonstrated that 400 mg and 600 mg once daily provided comparable efficacy. In contrast, the E-R analysis identified statistically significant relationships between higher drug exposure and toxicities as well as increased rates of treatment modifications, clearly favoring the 400 mg dose on the basis of safety. Based on these findings 400 mg once daily in combination with darolutamide has been selected as the RP3D for rinzimetostat.
Preliminary Efficacy Analysis at RP3D
As of March 6, 2026, radiographic progression-free survival (rPFS) was assessed in 18 efficacy-evaluable patients. PSA responses were assessed in a subset of 15 patients with at least one post-baseline assessment as of the January 16, 2026 clinical cutoff. ctDNA molecular response was evaluated in 14 patients with detectable ctDNA at baseline.
Early efficacy data, including landmark rPFS rates, PSA reductions and ctDNA responses, are suggestive of meaningful and durable clinical benefit for rinzimetostat in combination with darolutamide compared to competitor data and historical outcomes with approved therapies. Rinzimetostat 400 mg once daily in combination with darolutamide demonstrated compelling efficacy across multiple endpoints:
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With a median follow up of 4.9 months, landmark rPFS rates of 93%, 84%, and 84% at 3, 4, and 5 months, respectively, 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%.
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47% of patients (7/15) achieved a PSA50 response, with 33% (5/15) confirmed.
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Impressive ctDNA reductions observed across a range of AR mutations, with 71% of patients (10/14) achieving >50% ctDNA reduction.
Himalayas-1 Phase 3 Trial
The company expects to initiate the Himalayas-1 global Phase 3 registrational trial in mCRPC patients previously treated with abiraterone in the first half of 2026. This proposed trial will enroll approximately 600 patients from over 250 sites in over 20 countries, randomized 1:1 to receive the RP3D of 400 mg QD rinzimetostat in combination with darolutamide versus physician’s choice of an AR inhibitor or chemotherapy. The primary endpoint is rPFS, the key secondary endpoint is overall survival, and additional secondary endpoints include PSA response rate, objective response rate and patient reported outcomes.
In the US, the annual incidence of mCRPC patients previously treated with abiraterone is approximately 17,000, with an estimated addressable market of greater than $3.5 billion and total global addressable market of $7 billion. This market lacks oral, well-tolerated therapies with meaningful efficacy.
About ORIC Pharmaceuticals, Inc.
ORIC Pharmaceuticals is a clinical stage biopharmaceutical company dedicated to improving patients’ lives by Overcoming Resistance In Cancer. ORIC’s clinical stage product candidates include (1) rinzimetostat (ORIC-944), an allosteric inhibitor of the polycomb repressive complex 2 (PRC2) via the EED subunit, being developed for prostate cancer, and (2) enozertinib (ORIC-114), a brain-penetrant inhibitor targeting EGFR exon 20 and EGFR PACC mutations, being developed for NSCLC. ORIC has offices in South San Francisco and San Diego, California.