rinzimetostat (ORIC-944) / ORIC Pharma - LARVOL DELTA

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 (ESMO 2026) - No abstract available

Preclinical • Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer

Rinzimetostat, an Allosteric PRC2 Inhibitor Combined With Darolutamide: A Global Phase 3 Study in mCRPC Patients Previously Treated With Abiraterone Acetate (Himalayas-1) (ESMO 2026) - No abstract available

Clinical • P3 data • Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer

Anticipated Program Milestones1 (GlobeNewswire) - "ORIC anticipates the following upcoming milestones: Rinzimetostat in mCRPC: (i) 2H 2026: Program update; Enozertinib in NSCLC: (i) October 2026: 1L EGFR atypical monotherapy data to be presented at ESMO Congress 2026; (ii) 2H 2026: 1L EGFR exon 20 insertion monotherapy data and combination data with SC amivantamab."

Clinical data • EGFR exon 20 • Castration-Resistant Prostate Cancer • Non Small Cell Lung Cancer

A Study to Learn About the Investigational Drug Rinzimetostat (ORIC-944) in Patients With mCRPC Who Were Previously Treated With Abiraterone Acetate (Himalayas-1) (clinicaltrials.gov) - P3 | N=600 | Recruiting | Sponsor: ORIC Pharmaceuticals

New P3 trial • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

ORIC Pharmaceuticals Announces Three Presentations at the European Society for Medical Oncology (ESMO) Congress 2026 (Yahoo Finance) - "Enozertinib poster presentation to highlight data from an ongoing Phase 1b trial in first-line EGFR atypical NSCLC; Rinzimetostat trial-in-progress poster presentation to highlight the ongoing Himalayas-1 Phase 3 study design in patients with mCRPC previously treated with abiraterone; Rinzimetostat ePoster to highlight data supporting its potential to enhance AR signaling and restrict lineage plasticity in mCRPC."

P1 data • Preclinical • Trial status • Castration-Resistant Prostate Cancer • Non Small Cell Lung Cancer

ORIC Pharmaceuticals Announces Initiation of Himalayas-1 Phase 3 Trial in mCRPC Evaluating Rinzimetostat in Combination with NUBEQA (Darolutamide), Supported by Clinical Collaboration with Bayer (GlobeNewswire) - "The Himalayas-1 trial is expected to enroll approximately 600 patients from over 250 sites in 25 countries, randomized 1:1 to receive the RP3D of 400 mg once daily rinzimetostat (with or without food) in combination with darolutamide versus physician’s choice of an androgen receptor (AR) inhibitor or docetaxel....Under the terms of the agreement, ORIC will conduct and sponsor the Himalayas-1 trial and Bayer will provide their AR inhibitor, NUBEQA (darolutamide), at no cost for use in the trial in combination with rinzimetostat."

Licensing / partnership • Trial status • Castration-Resistant Prostate Cancer

ORIC-944-01: Study of ORIC-944 in Patients With Metastatic Prostate Cancer (clinicaltrials.gov) - P1 | N=275 | Recruiting | Sponsor: ORIC Pharmaceuticals | Trial completion date: Sep 2026 ➔ Apr 2028 | Trial primary completion date: Dec 2025 ➔ Jun 2027

Trial completion date • Trial primary completion date • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

ORIC anticipates the following upcoming milestones: Rinzimetostat in mCRPC (GlobeNewswire) - "(i) 1H 2026: Initiate Himalayas-1 global Phase 3 registrational trial in post-abiraterone mCRPC; (ii) 2H 2026: Program update."

Clinical • New P3 trial • Castration-Resistant Prostate Cancer

Rinzimetostat blockade of PRC2 activity, a key mechanism of treatment resistance, improves response of androgen receptor pathway inhibition across a spectrum of prostate cancer models (AACR 2026) - P1 | "Rinzimetostat in combination with the ARPI darolutamide demonstrated antitumor activity across a breadth of in vivo models representing the prostate cancer continuum and capturing a broad spectrum of treatment resistance settings including castration-sensitive and -resistant, ARPI-sensitive and -resistant, and AR-mutant and -wildtype. Thus, rinzimetostat represents a promising therapy to re-sensitize resistant tumors to ARPIs and block prostate tumor adaptation. Rinzimetostat is under clinical evaluation in combination with AR inhibitors in a global Phase 1b study (NCT05413421)."

Preclinical • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Genitourinary Neuroendocrine Carcinoma • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

Rinzimetostat, an allosteric EED inhibitor with best-in-class properties for the treatment of prostate cancer, is effective in PRC2 methyltransferase-resistant settings in preclinical studies (AACR 2026) - P1 | "As predicted from drug binding sites, EZH2 Y666N mutant-expressing prostate cancer cells were impervious to H3K27me3 reduction by EZH2 inhibitors mevrometostat or tazemetostat; however, rinzimetostat inhibited H3K27me3 in EZH2 Y666N mutant cells.Cells engineered with an EZH1/2 inhibitor acquired resistance mutant, EED H213R, demonstrated loss of effectiveness upon treatment with EZH1/2 inhibitor valemetostat, whereas rinzimetostat equally inhibited H3K27me3 in the EED mutant and wildtype settings. Together, these data suggest that rinzimetostat, as an EED inhibitor, has the potential for superiority in EZH2 and EZH1/2 inhibitor-acquired resistance contexts.In summary, preclinical results demonstrate potential best-in-class drug properties of rinzimetostat, as well as the potential superiority of targeting EED to address paralog compensation and avoid acquired resistance mechanisms that may be liabilities for EZH2 or EZH1/2 inhibitors. Rinzimetostat is under clinical..."

Preclinical • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • EZH2 • SUZ12

Combining PRC2 inhibitors with metronomic chemotherapy: A promising therapeutic strategy for diffuse large B-cell lymphoma (AACR 2026) - "In vitro proliferation assays were performed on both EZH2Y641F mutant (SU-DHL10) and EZH2 wild-type (OCI-LY3, Toledo) DLBCL cell lines exposed to thrice-weekly vinorelbine (mVNR) and daily PRC2 inhibitors (PRC2i: tazemetostat, valemetostat, ORIC-944), alone and in concomitant combination, for 144h. These findings offer a solid rationale for combining PRC2i and mCHEMO as an encouraging therapeutic approach for DLBCL, particularly in elderly or fragile patients, due to their low toxicity profiles. Overall, these results warrant additional in vitro investigations to elucidate the mechanisms underlying the reported effects and in vivo experiments in DLBCL models to validate our new therapeutic strategy, which holds potential for rapid translation into future clinical trials."

IO biomarker • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • EZH2

Embryonic ectoderm development protein (EED) inhibitor APG-5918 exhibits potent antitumor activity and synergizes with androgen receptor (AR) inhibitor enzalutamide in preclinical prostate cancer (PCa) models (AACR 2025) - "APG-5918 appeared to be more potent than two EZH2 inhibitors (tazemetostat, PF-06821497) and EED inhibitor ORIC-944 under the same experimental condition. APG-5918 alone or in combination with enzalutamide exhibited antitumor activity in preclinical PCa models, supporting EED inhibition (± AR antagonists) as a therapeutic strategy for PCa."

Preclinical • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CCND1 • CDK4 • DNMT1 • MCL1 • SUZ12 • UHRF1

ORIC Pharmaceuticals Presents Preclinical Data to Support the Potential of Rinzimetostat Across Prostate Cancer and in Emerging Resistance Settings at the 2026 American Association for Cancer Research (AACR) Annual Meeting (GlobeNewswire) - "Rinzimetostat in combination with darolutamide demonstrated antitumor activity across a breadth of in vivo models representing the prostate cancer continuum, including CSPC and CRPC....Rinzimetostat retained antitumor activity in prostate cancer cells with overexpressed EZH1 in vitro, while potency was diminished for mevrometostat or tazemetostat. Preclinical studies show that rinzimetostat overcomes acquired resistance mechanisms observed in the clinic for tazemetostat and valemetostat."

Preclinical • Castration-Resistant Prostate Cancer

ORIC-944, a potent and selective allosteric PRC2 inhibitor with best-in-class properties, demonstrates combination synergy with AR pathway inhibitors in prostate cancer models (AACR 2024) - P1 | "RNA-seq analysis of transcriptional changes induced by ORIC-944 provided mechanistic insight into the role of PRC2 in prostate cancer lineage plasticity and combination response.These results position ORIC-944 as a best-in-class PRC2 inhibitor for evaluation in combination with ARPI in patients with metastatic prostate cancer. A phase 1b trial of ORIC-944 is ongoing (NCT05413421)."

Preclinical • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • SUZ12

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 (AACR 2025) - P1 | "These results position ORIC-944 as a potential best-in-class PRC2 inhibitor that blocks prostate tumor adaptation, restores luminal features, and sensitizes tumors to ARPI. A phase 1b trial of ORIC-944 in combination with ARPIs is ongoing in metastatic prostate cancer (NCT05413421)."

Preclinical • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Discovery of ORIC-944, a novel inhibitor of PRC2 with best-in-class properties for the treatment of prostate cancer (AACR 2024) - P1 | "Characterization of ORIC-944 revealed superiority to first generation clinical PRC2 inhibitors across a variety of preclinical assessments including potency, solubility, CYP inhibition/induction, PK and oral bioavailability. Together, the preclinical results indicate the desired properties were achieved in ORIC-944 to meet a superior target candidate profile, and the ongoing phase 1b trial (NCT05413421) demonstrates a clinical half-life of approximately 20 hours consistent with once daily dosing and a potential best-in-class profile."

Follicular Lymphoma • Genito-urinary Cancer • Hematological Malignancies • Lymphoma • Oncology • Prostate Cancer • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

ORIC Pharmaceuticals Reports Selection of Rinzimetostat RP3D in Combination with Darolutamide for Himalayas-1 Phase 3 Global Study with Dose Optimization Data Supporting Its Potential Best-in-Disease Profile (GlobeNewswire) - "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. 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. 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."

New P3 trial • P1 data • Castration-Resistant Prostate Cancer

ORIC Pharmaceuticals…announced that it will report combination dose optimization data from the Phase 1b trial of rinzimetostat (ORIC-944) in patients with metastatic castration resistant prostate cancer (mCRPC) in a conference call and webcast on Tuesday, March 31, 2026 at 4:30pm ET (GlobeNewswire)

P1 data • Castration-Resistant Prostate Cancer

Title: Rinzimetostat, an allosteric EED inhibitor with best-in-class properties for the treatment of prostate cancer, is effective in PRC2 methyltransferase-resistant settings in preclinical studies (GlobeNewswire) - "...Abstracts...have been accepted for poster presentations at the 2026 American Association for Cancer Research (AACR) Annual Meeting....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."

Preclinical • Prostate Cancer

Title: Rinzimetostat blockade of PRC2 activity, a key mechanism of treatment resistance, improves response of androgen receptor pathway inhibition across a spectrum of prostate cancer models (GlobeNewswire) - "...Abstracts...have been accepted for poster presentations at the 2026 American Association for Cancer Research (AACR) Annual Meeting....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."

Preclinical • Castration-Resistant Prostate Cancer

ORIC anticipates the following upcoming milestones (GlobeNewswire) - "Rinzimetostat in mCRPC: 1Q 2026: Combination dose optimization data with AR inhibitor; 1H 2026: Initiate first global Phase 3 registrational trial in mCRPC...2H 2026: Program update Enozertinib in NSCLC: 2H 2026: 1L EGFR exon 20 monotherapy data and combination data with SC amivantamab; 2H 2026: 1L EGFR PACC monotherapy data."

Clinical data • EGFR exon 20 • New P3 trial • Castration-Resistant Prostate Cancer • Non Small Cell Lung Cancer

Anticipated Program Milestones (GlobeNewswire) - "ORIC anticipates the following upcoming data milestones: ORIC-944 (mCRPC): (i)1Q 2026: Combination dose optimization data with AR inhibitor(s)."

P1 data • Prostate Cancer

ORIC Pharmaceuticals Announces Completion of Dose Exploration Portion of ORIC-944 Phase 1b Clinical Trial and Continues to Demonstrate Potential Best-in-Class Efficacy and Safety (GlobeNewswire) - "55% of patients (11/20) achieved a PSA50 response, confirmed in 40% (8/20). 20% of patients (4/20) achieved a PSA90 response (all confirmed)....Rapid and deep ctDNA responses across a breadth of AR mutations and other gene alterations, with 76% of patients (13/17) achieving >50% ctDNA reduction....'We look forward to sharing dose optimization data in 1Q 2026 ahead of initiating our first global Phase 3 registrational trial in mCRPC in the first half of next year'."

New P3 trial • P1 data • Trial status • Castration-Resistant Prostate Cancer

PRC2 inhibition enhances KRAS inhibitor response to delay treatment relapse in KRAS-mutant preclinical lung and colorectal cancer models (AACR-NCI-EORTC 2025) - P1 | "The combination of adagrasib, a KRAS G12C inhibitor, and ORIC-944 resulted in greater antitumor efficacy, more tumor regressions, and significantly smaller tumors, in both CRC and NSCLC models. Combining ORIC-944 with KRAS inhibition significantly improved efficacy and PFS in NSCLC and CRC models, demonstrating that PRC2 inhibition can deepen and extend KRAS inhibitor responses to prevent or delay resistance to KRAS inhibition. ORIC-944 is under clinical evaluation in a global Phase 1b study (NCT05413421)."

Preclinical • Breast Cancer • Colorectal Cancer • Genito-urinary Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Prostate Cancer • Solid Tumor • Triple Negative Breast Cancer • KRAS

PRC2 inhibition enhances AR inhibitor response to delay treatment relapse in castration-sensitive prostate cancer by restricting adaptation of tumor cells in preclinical studies (AACR-NCI-EORTC 2025) - P1 | "In vivo xenografts were dosed with ORIC-944 or EZH2 inhibitor mevrometostat, darolutamide, or the combinations...Transcriptional effects induced by combining ORIC-944 and ARI were comparable irrespective of ARI (i.e. darolutamide, apalutamide or enzalutamide)... These preclinical results position ORIC-944 as a potential best-in-class PRC2 inhibitor that induces luminal cell fate and restricts lineage TF accessibility in both CRPC and CSPC settings, thereby extending the duration of response to ARI treatment by disabling cellular plasticity and delaying prostate tumor adaptation. ORIC-944 is under clinical evaluation in combination with ARIs in a global Phase 1b study (NCT05413421)."

Preclinical • Tumor cell • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Hormone Sensitive Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor • FOXA1 • HNF1A • ONECUT2