ORIC® Pharmaceuticals Presents Preclinical Data to Support the Potential of ORIC-944 as a Best-in-Class PRC2 Inhibitor for the Treatment of Prostate Cancer at the 2025 American Association for Cancer Research (AACR) Annual Meeting

Rhea-AI Summary

ORIC Pharmaceuticals presented promising preclinical data for their drug ORIC-944 at the 2025 AACR Annual Meeting. The drug, a selective PRC2 inhibitor, showed significant potential in treating prostate cancer when combined with standard treatments.

Key findings include:

• Increased progression-free survival when combined with androgen receptor pathway inhibitors (ARPIs)
• Demonstrated both transcriptional and antitumor synergy with ARPIs
• Showed robust PRC2 inhibition and enhanced luminal cell state
• Prevented tumor adaptation through chromatin remodeling

The drug is currently in Phase 1b trials, being tested in combination with two established treatments: ERLEADA (apalutamide) and NUBEQA (darolutamide). Chief Scientific Officer Lori Friedman highlighted ORIC-944's potential to be a best-in-class treatment across different stages of prostate cancer.

This development represents a significant step forward in addressing therapeutic resistance in prostate cancer treatment, positioning ORIC-944 as a promising candidate for both castration-resistant and castration-sensitive prostate cancer.

Positive

• ORIC-944 demonstrated synergistic activity with current prostate cancer treatments (ARPIs)
• Preclinical data showed improved progression-free survival in both castration-resistant and castration-sensitive prostate cancer models
• Drug shows potential as best-in-class PRC2 inhibitor through dual mechanism (transcriptional and chromatin)
• Currently in Phase 1b trial testing combinations with established drugs ERLEADA and NUBEQA

Negative

• Results are only from preclinical studies, not yet proven in humans
• Early-stage clinical development (Phase 1b) indicates long pathway to potential commercialization

Insights

Oncology Research Scientist

ORIC-944 shows promising preclinical synergy with prostate cancer treatments, advancing to Phase 1b with meaningful mechanistic advantages.

The preclinical data presented by ORIC Pharmaceuticals at AACR 2025 reveals significant potential for their PRC2 inhibitor ORIC-944 in prostate cancer treatment. As a potent, highly selective, orally bioavailable allosteric inhibitor, this compound demonstrated compelling synergistic activity when combined with standard androgen receptor pathway inhibitors (ARPIs).

What stands out from a mechanistic perspective is ORIC-944's ability to work through both transcriptional and chromatin mechanisms, effectively blocking tumor adaptation while restoring luminal features. This dual approach directly addresses a fundamental challenge in prostate cancer treatment: the cellular plasticity that typically leads to treatment resistance.

The data showing improved progression-free survival in both castration-resistant and castration-sensitive prostate cancer models represents a meaningful advance. By restricting lineage transcription factor accessibility through chromatin remodeling, ORIC-944 appears to maintain cancer cells in a more differentiated state, preventing access to plasticity programs that would otherwise enable treatment evasion.

The ongoing Phase 1b clinical trial evaluating ORIC-944 in combination with ERLEADA® (apalutamide) and NUBEQA® (darolutamide) will provide crucial insights on whether these preclinical benefits translate to patients. The comprehensive approach targeting both transcriptional and chromatin mechanisms positions ORIC-944 as potentially addressing key resistance pathways in prostate cancer treatment.

Biotech Investment Analyst

ORIC's PRC2 inhibitor demonstrates synergy with approved prostate cancer drugs, strengthening clinical positioning despite early-stage status.

ORIC Pharmaceuticals' presentation of preclinical data for ORIC-944 represents meaningful validation for their PRC2 inhibition approach in prostate cancer. The demonstrated synergistic activity when combined with established androgen receptor pathway inhibitors (ARPIs) suggests a complementary rather than competitive market positioning strategy that could enhance adoption if eventually approved.

The company has made strategic progress by advancing this candidate into a Phase 1b clinical trial, evaluating combinations with two established treatments: ERLEADA® (apalutamide) and NUBEQA® (darolutamide). This combination approach addresses resistance mechanisms in prostate cancer treatment, potentially extending clinical benefit of these existing therapies.

From a development perspective, the compound's mechanism is particularly noteworthy. By enhancing the luminal cell state and preventing access to plasticity programs, ORIC-944 targets fundamental mechanisms of treatment resistance rather than merely providing symptomatic relief.

The preclinical efficacy demonstrated in both castration-resistant and castration-sensitive models broadens potential applications across the prostate cancer treatment spectrum, potentially expanding the addressable patient population if clinical trials prove successful.

While these preclinical results show scientific progress, investors should recognize that ORIC-944 remains in early clinical development. The upcoming Phase 1b results will provide critical insights into whether the observed preclinical synergy translates to patients, along with establishing the safety profile of these combinations.

SOUTH SAN FRANCISCO, Calif. and SAN DIEGO, April 28, 2025 (GLOBE NEWSWIRE) -- ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, today announced the presentation of a poster at the 2025 American Association for Cancer Research (AACR) Annual Meeting, highlighting preclinical data on ORIC-944, a potent, highly selective, orally bioavailable allosteric inhibitor of PRC2, which demonstrated synergistic activity and improved progression-free survival (PFS) when combined with androgen receptor pathway inhibitors (ARPIs) in models of prostate cancer.

“We are excited by the potential of ORIC-944 to be a best-in-class PRC2 inhibitor for the treatment of prostate cancer,” said Lori Friedman, PhD, chief scientific officer. “The data presented at AACR demonstrate the strong synergy of ORIC-944 when combined with standards of care, reversing the evolution of prostate cancer, and improving progression-free survival in both castration-resistant and castration-sensitive prostate cancer models - validating the clinical exploration of ORIC-944 across the continuum of prostate cancer.”

Poster presentation:

ORIC-944, a PRC2 inhibitor with best-in-class properties, restores luminal features and restricts adaptation in prostate cancer models, conferring synergy with AR pathway inhibitors

Key findings of the presentation:

• ORIC-944 increased progression-free survival (PFS) when combined with ARPIs in both castration-sensitive and castration-resistant prostate cancer models.
• ORIC-944 demonstrated transcriptional synergy and antitumor synergy when combined with ARPIs in prostate cancer cells.
• In preclinical prostate cancer models, ORIC-944 demonstrated robust inhibition of PRC2, enhanced luminal cell state, and consistently restricted lineage transcription factor accessibility through chromatin remodeling, ​thereby reenforcing the luminal state and preventing access to plasticity programs.
• Results position ORIC-944 as a potential best-in-class PRC2 inhibitor that, through both transcriptional and chromatin mechanisms, blocks prostate tumor adaptation, restores luminal features, and sensitizes tumors to ARPIs.
• ORIC-944 is currently being evaluated in combination with ERLEADA® (apalutamide) and in combination with NUBEQA® (darolutamide) in an ongoing Phase 1b trial for prostate cancer.
  

About ORIC-944
ORIC-944 is a potent and selective allosteric inhibitor of the polycomb repressive complex 2 (PRC2) via the embryonic ectoderm development (EED) subunit that demonstrates best-in-class drug properties in preclinical studies, including potency, solubility, and pharmacokinetics, with half-life supporting once daily dosing. ORIC-944 was initially evaluated as a single agent in a Phase 1b trial in patients with advanced prostate cancer and demonstrated potential best-in-class drug properties, including clinical half-life of approximately 20 hours, robust target engagement and a favorable safety profile. ORIC-944 is currently being evaluated in combination with ERLEADA^® (apalutamide) and in combination with NUBEQA^® (darolutamide) in an ongoing Phase 1b trial for 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) ORIC-944, an allosteric inhibitor of the polycomb repressive complex 2 (PRC2) via the EED subunit, being developed for prostate cancer, and (2) ORIC-114, a brain penetrant inhibitor that selectively targets EGFR exon 20, HER2 exon 20 and EGFR atypical mutations, being developed across multiple genetically defined cancers. Beyond these two product candidates, ORIC^® is also developing multiple precision medicines targeting other hallmark cancer resistance mechanisms. 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, statements regarding the advantages of ORIC-944 in preclinical models, including synergies with AR pathway inhibitors and improved PFS; the continued clinical development of ORIC-944; the potential best-in-class properties of ORIC-944; the potential advantages of ORIC-944 and ORIC’s other programs; 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 ORIC’s 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 titled “Risk Factors” in ORIC’s Annual Report on Form 10-K filed with the Securities and Exchange Commission (the “SEC”) on February 18, 2025, 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
dominic.piscitelli@oricpharma.com
info@oricpharma.com

FAQ

What did ORIC Pharmaceuticals (ORIC) present at AACR 2025 for prostate cancer treatment?

ORIC presented data on ORIC-944, a PRC2 inhibitor that showed improved progression-free survival when combined with androgen receptor pathway inhibitors in prostate cancer models. The drug demonstrated synergistic activity in both castration-resistant and castration-sensitive prostate cancer.

How does ORIC-944 work with existing prostate cancer treatments?

ORIC-944 works synergistically with AR pathway inhibitors (ARPIs) like ERLEADA and NUBEQA. It blocks tumor adaptation, restores luminal features, and makes tumors more sensitive to ARPIs through both transcriptional and chromatin mechanisms.

What are the key findings of ORIC-944's preclinical trials in 2025?

ORIC-944 showed robust PRC2 inhibition, enhanced luminal cell state, and restricted lineage transcription factor accessibility. It demonstrated both transcriptional and antitumor synergy when combined with AR pathway inhibitors, improving progression-free survival in prostate cancer models.

Which clinical trials is ORIC-944 currently undergoing?

ORIC-944 is currently in Phase 1b trials, being evaluated in combination with two drugs: ERLEADA (apalutamide) and NUBEQA (darolutamide) for prostate cancer treatment.

What makes ORIC-944 a potential best-in-class PRC2 inhibitor for prostate cancer?

ORIC-944 is considered potentially best-in-class due to its potent, highly selective, and orally bioavailable properties. It effectively reverses prostate cancer evolution and shows strong synergy with standard treatments across different types of prostate cancer.