ORIC® Pharmaceuticals Presents Preclinical and Translational Data to Support the Potential of Rinzimetostat to Enhance Sensitivity to Androgen Receptor Inhibition in Prostate Cancer at ESMO Congress 2026

Preclinical data highlight potential advantages of targeting PRC2 via EED over EZH2, including the emergence of resistance mutations to EZH2 inhibitors like mevrometostat and against which the EED inhibitor rinzimetostat maintained effectiveness

Preclinical results, supported by translational data in mCRPC patient samples, show rinzimetostat reinforces a luminal, AR-dependent state, restricts lineage plasticity and enhances sensitivity to AR inhibition

Findings reinforce rinzimetostat’s differentiated profile and support development across the prostate cancer disease spectrum, including in the ongoing Himalayas-1 Phase 3 trial

SOUTH SAN FRANCISCO, Calif. and SAN DIEGO, Oct. 23, 2026 (GLOBE NEWSWIRE) — ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing and commercializing treatments that address mechanisms of therapeutic resistance, today announced preclinical and translational data from an ePoster presentation at ESMO Congress 2026 highlighting the potential of rinzimetostat to enhance sensitivity to androgen receptor inhibition in prostate cancer.

“These results strengthen the rationale for combining PRC2 inhibition with androgen receptor targeted therapies across castration-sensitive and castration-resistant prostate cancer by limiting tumor adaptability and enhancing sensitivity to AR inhibition,” said Lori Friedman, PhD, chief scientific officer. “Verification of our preclinical results in patient samples, together with the potential advantages of targeting PRC2 via EED, reinforce our confidence in rinzimetostat’s potential best-in-class profile and support its evaluation across the prostate cancer disease spectrum, including in our ongoing Himalayas-1 Phase 3 trial.”

Rinzimetostat, a Next Generation PRC2 Inhibitor, Enhances Luminal Fate and AR Signaling While Restricting Lineage Plasticity in Preclinical Models and Demonstrates Mechanistic Proof-of-Concept in Samples from Patients with mCRPC

ePoster Number: 1128eP
Session Title: Developmental Therapeutics
Key findings of the presentation:

• Preclinical results suggest potential advantages of targeting PRC2 via EED with rinzimetostat over targeting EZH2:
  • Prostate cancer cells that rapidly developed resistance to mevrometostat acquired a mutation in EZH2 against which rinzimetostat potency was maintained; no emergence of rinzimetostat-resistant cells was observed.
  • No hematologic tumorigenesis was observed in the rinzimetostat rat toxicology study, in contrast to rat tumorigenesis demonstrated with EZH2 inhibitor tazemetostat; these results are consistent with mouse genetic studies of PRC2 components and suggest the tumorigenesis risk may be elevated with selective EZH2 targeting.
  • Comparative preclinical studies demonstrated drug properties supporting rinzimetostat’s potential best-in-class profile, including favorable solubility, oral bioavailability, half-life and CYP profile.
• Rinzimetostat restored access to AR binding motifs and restricted accessibility at sites associated with lineage plasticity in preclinical prostate cancer models, supporting a mechanism that reinforces AR dependence and limits tumor adaptation.
  • Rinzimetostat synergized with AR inhibition in preclinical prostate cancer studies.
  • KLK2 and STEAP1 luminal markers increased following rinzimetostat treatment in preclinical studies.
• Samples from patients with mCRPC treated with single-agent rinzimetostat demonstrated biological changes consistent with the preclinical findings:
  • Plasma cfDNA methylation profiling showed epigenetic shifts indicative of increased AR signaling after one treatment cycle in most patients assessed.
  • Paired tumor biopsies showed increased levels of luminal and AR-associated markers PSMA and KLK2.

The ePoster presentation can be found on the ESMO Congress website here, and in the publication section of ORIC’s website here.

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, an allosteric inhibitor of the polycomb repressive complex 2 (PRC2) via the EED subunit, being developed for prostate cancer, and (2) enozertinib, a brain-penetrant inhibitor targeting EGFR atypical and EGFR exon 20 mutations, being developed for NSCLC. ORIC has offices in South San Francisco and San Diego, California. For more information, please go to www.oricpharma.com, and follow us on X or LinkedIn.

Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements as that term is defined in Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Statements in this press release that are not purely historical are forward-looking statements. Such forward-looking statements include, among other things, the continued clinical development of rinzimetostat; the potential advantages of rinzimetostat, including by targeting PRC2 via EED instead of EZH2; statements regarding the potential best-in-class profile of rinzimetostat; the development plans and timelines for rinzimetostat; plans underlying ORIC’s clinical trials and development; and statements by the company’s chief scientific officer. Words such as “believes,” “anticipates,” “plans,” “expects,” “intends,” “will,” “goal,” “potential” and similar expressions are intended to identify forward-looking statements. The forward-looking statements contained herein are based upon ORIC’s current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results could differ materially from those projected in any forward-looking statements due to numerous risks and uncertainties, including but not limited to: risks associated with the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics and operating as an early clinical stage company; ORIC’s ability to develop, initiate or complete preclinical studies and clinical trials for, obtain approvals for and commercialize any of its product candidates; changes in ORIC’s plans to develop and commercialize its product candidates; the potential for clinical trials of rinzimetostat, enozertinib or any other product candidates to differ from preclinical, initial, interim, preliminary or expected results; negative impacts of health emergencies, economic instability or international conflicts on ORIC’s operations, including clinical trials; the risk of the occurrence of any event, change or other circumstance that could give rise to the termination of ORIC’s license and collaboration agreements or its clinical trial collaboration and supply agreements; the potential market for ORIC’s product candidates, and the progress and success of competing therapeutics currently available or in development; ORIC’s ability to raise any additional funding it will need to continue to pursue its business and product development plans; regulatory developments in the United States and foreign countries; ORIC’s reliance on third parties, including contract manufacturers and contract research organizations; ORIC’s ability to obtain and maintain intellectual property protection for its product candidates; the loss of key scientific or management personnel; competition in the industry in which ORIC operates; general economic and market conditions; and other risks. Information regarding the foregoing and additional risks may be found in the section entitled “Risk Factors” in ORIC’s Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (the SEC) on August 3, 2026, and ORIC’s future reports to be filed with the SEC. These forward-looking statements are made as of the date of this press release, and ORIC assumes no obligation to update the forward-looking statements, or to update the reasons why actual results could differ from those projected in the forward-looking statements, except as required by law.

Contact:

Dominic Piscitelli, Chief Financial Officer
[email protected]
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