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
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.
ORIC Pharmaceuticals ha presentato dati preclinici promettenti per il loro farmaco ORIC-944 al Meeting Annuale AACR 2025. Il farmaco, un inibitore selettivo di PRC2, ha mostrato un significativo potenziale nel trattamento del cancro alla prostata quando combinato con terapie standard.
Risultati chiave includono:
- Aumento della sopravvivenza libera da progressione se associato a inibitori della via del recettore degli androgeni (ARPI)
- Sinergia sia trascrizionale che antitumorale dimostrata con gli ARPI
- Robusta inibizione di PRC2 e potenziamento dello stato delle cellule luminali
- Prevenzione dell’adattamento tumorale tramite rimodellamento della cromatina
Attualmente il farmaco è in fase 1b di sperimentazione, testato in combinazione con due trattamenti consolidati: ERLEADA (apalutamide) e NUBEQA (darolutamide). La Chief Scientific Officer Lori Friedman ha sottolineato il potenziale di ORIC-944 come trattamento di eccellenza in diversi stadi del cancro alla prostata.
Questo sviluppo rappresenta un progresso significativo nel superare la resistenza terapeutica nel trattamento del cancro alla prostata, posizionando ORIC-944 come un candidato promettente sia per il cancro alla prostata resistente alla castrazione sia per quello sensibile alla castrazione.
ORIC Pharmaceuticals presentó datos preclínicos prometedores de su fármaco ORIC-944 en la Reunión Anual AACR 2025. El medicamento, un inhibidor selectivo de PRC2, mostró un potencial significativo en el tratamiento del cáncer de próstata cuando se combina con tratamientos estándar.
Los hallazgos clave incluyen:
- Aumento de la supervivencia libre de progresión al combinarse con inhibidores de la vía del receptor de andrógenos (ARPI)
- Sinergia tanto transcripcional como antitumoral demostrada con los ARPI
- Fuerte inhibición de PRC2 y mejora del estado de las células luminales
- Prevención de la adaptación tumoral mediante la remodelación de la cromatina
Actualmente, el fármaco se encuentra en ensayos de fase 1b, siendo probado en combinación con dos tratamientos establecidos: ERLEADA (apalutamida) y NUBEQA (darolutamida). La directora científica Lori Friedman destacó el potencial de ORIC-944 para ser un tratamiento de primera clase en diferentes etapas del cáncer de próstata.
Este avance representa un paso significativo para abordar la resistencia terapéutica en el tratamiento del cáncer de próstata, posicionando a ORIC-944 como un candidato prometedor tanto para el cáncer de próstata resistente a la castración como para el sensible a la castración.
ORIC Pharmaceuticals는 2025년 AACR 연례회의에서 자사의 약물 ORIC-944에 대한 유망한 전임상 데이터를 발표했습니다. 이 약물은 선택적 PRC2 억제제로, 표준 치료제와 병용 시 전립선암 치료에 큰 잠재력을 보였습니다.
주요 발견 사항은 다음과 같습니다:
- 안드로겐 수용체 경로 억제제(ARPI)와 병용 시 무진행 생존 기간 증가
- ARPI와의 전사 및 항종양 시너지 효과 확인
- 강력한 PRC2 억제 및 루미날 세포 상태 강화
- 염색질 재구성을 통한 종양 적응 방지
현재 이 약물은 1b상 임상시험 중이며, 두 가지 기존 치료제인 ERLEADA(아팔루타마이드)와 NUBEQA(다롤루타마이드)와 병용하여 시험되고 있습니다. 최고 과학 책임자 로리 프리드먼은 ORIC-944가 전립선암의 다양한 단계에서 최고 수준의 치료제가 될 잠재력이 있다고 강조했습니다.
이번 개발은 전립선암 치료에서 치료 저항성을 극복하는 데 중요한 진전을 의미하며, ORIC-944를 거세 저항성 및 거세 민감성 전립선암 모두에 유망한 후보로 자리매김하게 합니다.
ORIC Pharmaceuticals a présenté des données précliniques prometteuses pour leur médicament ORIC-944 lors de la réunion annuelle AACR 2025. Ce médicament, un inhibiteur sélectif de PRC2, a montré un potentiel significatif dans le traitement du cancer de la prostate lorsqu'il est combiné aux traitements standards.
Les principales conclusions sont :
- Augmentation de la survie sans progression lorsqu'il est associé aux inhibiteurs de la voie du récepteur aux androgènes (ARPI)
- Synergie transcriptionnelle et antitumorale démontrée avec les ARPI
- Inhibition robuste de PRC2 et amélioration de l'état des cellules luminales
- Prévention de l'adaptation tumorale grâce au remodelage de la chromatine
Le médicament est actuellement en essais de phase 1b, testé en combinaison avec deux traitements établis : ERLEADA (apalutamide) et NUBEQA (darolutamide). La directrice scientifique Lori Friedman a souligné le potentiel d’ORIC-944 à devenir un traitement de référence à différents stades du cancer de la prostate.
Cette avancée représente un pas important dans la lutte contre la résistance thérapeutique dans le traitement du cancer de la prostate, positionnant ORIC-944 comme un candidat prometteur pour le cancer de la prostate résistant et sensible à la castration.
ORIC Pharmaceuticals präsentierte vielversprechende präklinische Daten zu ihrem Medikament ORIC-944 auf dem AACR-Jahrestreffen 2025. Das Medikament, ein selektiver PRC2-Inhibitor, zeigte erhebliches Potenzial bei der Behandlung von Prostatakrebs in Kombination mit Standardtherapien.
Wesentliche Erkenntnisse umfassen:
- Erhöhte progressionsfreie Überlebenszeit bei Kombination mit Androgenrezeptor-Weg-Inhibitoren (ARPI)
- Nachgewiesene transkriptionelle und antitumorale Synergie mit ARPI
- Starke PRC2-Hemmung und verstärkter luminaler Zellzustand
- Verhinderung der Tumoradaptation durch Chromatin-Remodellierung
Das Medikament befindet sich derzeit in Phase-1b-Studien und wird in Kombination mit zwei etablierten Behandlungen getestet: ERLEADA (Apalutamid) und NUBEQA (Darolutamid). Die Chief Scientific Officer Lori Friedman hob das Potenzial von ORIC-944 hervor, eine erstklassige Behandlung für verschiedene Stadien des Prostatakrebses zu werden.
Diese Entwicklung stellt einen bedeutenden Fortschritt bei der Überwindung therapeutischer Resistenz in der Prostatakrebsbehandlung dar und positioniert ORIC-944 als vielversprechenden Kandidaten für kastrationsresistenten und kastrationssensitiven Prostatakrebs.
- 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
- Results are only from preclinical studies, not yet proven in humans
- Early-stage clinical development (Phase 1b) indicates long pathway to potential commercialization
Insights
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
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
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:
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
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