ORIC® Pharmaceuticals Announces Preclinical Rinzimetostat (ORIC-944) Presentations at the 2026 American Association for Cancer Research (AACR) Annual Meeting

SOUTH SAN FRANCISCO, Calif. and SAN DIEGO, March 17, 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 that multiple abstracts highlighting the potential of rinzimetostat (ORIC-944), a potent and selective allosteric inhibitor of PRC2 to treat prostate cancer, have been accepted for poster presentations at the 2026 American Association for Cancer Research (AACR) Annual Meeting taking place April 17-22, 2026 in San Diego, CA. All regular abstracts are available for viewing via AACR's online itinerary planner located here.

Poster presentations details:

Abstract Highlights

Rinzimetostat is a potent and highly selective next-generation allosteric PRC2 inhibitor targeting the EED subunit that has demonstrated potential best-in-class efficacy and safety in a dose exploration trial in combination with androgen receptor (AR) inhibitors. To further evaluate the possible benefits of inhibiting PRC2 activity through EED targeting, preclinical studies investigated rinzimetostat versus EZH2- or EZH1/2-targeting agents in the context of proposed acquired resistance mechanisms. Biochemical assays demonstrated that rinzimetostat maintained potent inhibition of PRC2 complexes containing either EZH1 or EZH2 as the enzymatic subunit, while EZH2 or EZH1/2 dual inhibitors showed reduced activity in EZH1-containing complexes. Consistent with the biochemical data, rinzimetostat retained antitumor activity in prostate cancer cells overexpressing EZH1, while EZH2 inhibitors mevrometostat and tazemetostat lost potency in this context. Rinzimetostat also maintained inhibition of H3K27me3 in prostate cancer cells expressing the clinically reported EZH2-inhibitor acquired resistance mutation EZH2 Y666N, while EZH2 inhibitors did not reduce H3K27me3. In addition, in prostate cancer cells expressing the acquired resistance mutation EED-H213R, which is associated with clinical resistance to dual EZH1/2 inhibition, rinzimetostat equally inhibited H3K27me3 in both mutant and wild-type settings, while an EZH1/2 inhibitor did not. Together, these data suggest that rinzimetostat, as an EED inhibitor, has the potential for superiority in resistance context of EZH1 overexpression, as well as in acquired resistance mutant contexts of EZH2 and EZH1/2 inhibitors. A global phase 1b trial of rinzimetostat in combination with AR inhibitors is ongoing in metastatic prostate cancer (NCT05413421).

Abstract Highlights

Rinzimetostat is a potent and highly selective next-generation allosteric PRC2 inhibitor targeting the EED subunit that has demonstrated potential best-in-class efficacy and safety in a dose exploration trial in combination with AR inhibitors. Transcriptome analyses of more than 1,000 prostate cancer patient samples spanning primary prostate cancer, metastatic castration-resistant prostate cancer (mCRPC), and neuroendocrine prostate cancer (NEPC) revealed gene expression patterns driving prostate cancer progression. Pseudotime analysis of tumor transcriptomes highlighted the eventual reduction in AR expression, AR signaling and luminal identity during mCRPC that may reflect lineage plasticity and cell state reprogramming. Integrated analysis across treatment lines identified epigenetic regulators, including PRC2, whose activity signatures increase during disease progression and may contribute to tumor heterogeneity and resistance to androgen receptor pathway inhibitors (ARPIs), further supporting the rationale for PRC2 inhibition. Rinzimetostat in combination with the AR inhibitor darolutamide demonstrated antitumor activity across a broad spectrum of in vivo prostate cancer models representing the treatment continuum, including castration-sensitive and castration-resistant disease, ARPI-sensitive and ARPI-resistant settings, and tumors harboring both AR-mutant and AR wild-type backgrounds. Together, these findings suggest that targeting PRC2 with rinzimetostat re-sensitizes ARPI-resistant tumors to AR pathway inhibition and blocks prostate tumor adaptation. A global phase 1b trial of rinzimetostat in combination with AR inhibitors is ongoing in metastatic prostate cancer (NCT05413421).

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, 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. 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 (ORIC-944); the potential advantages of rinzimetostat; clinical outcomes, which may materially change as patient enrollment continues or more patient data become available; statements regarding the potential best-in-class properties of rinzimetostat; and plans underlying ORIC's clinical trials and development. 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 Annual Report on Form 10-K filed with the Securities and Exchange Commission (the SEC) on February 23, 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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