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

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

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 • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

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

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

ORIC Pharmaceuticals Presented Preclinical Data at the EORTC-NCI-AACR International Conference on Molecular Targets and Cancer Therapeutics Supporting Best-in-Class Potential of ORIC-944 to Treat Patients With Prostate Cancer and Other Solid Tumors (GlobeNewswire) - "Mechanistically, ORIC-944 in combination with AR inhibition in CSPC was linked to increased luminal cell state, and the restriction of lineage adaptation through reduced chromatin accessibility at binding sites of transcription factors associated with lineage diversification and cell plasticity...ORIC-944 is a potential best-in-class PRC2 inhibitor that, when combined with KRAS inhibition, significantly improved efficacy and progression-free survival in KRAS G12C mutant non-small cell lung cancer (NSCLC) and colorectal cancer (CRC) models."

Preclinical • Colorectal Cancer • Non Small Cell Lung Cancer • Prostate Cancer

ORIC Pharmaceuticals Expands Leadership Team with the Appointment of Kevin Brodbeck as Chief Technical Officer (GlobeNewswire) - "The creation of the CTO role and Dr. Brodbeck’s appointment reflect the impending advancement of ORIC’s clinical programs into late-stage development with the potential start of Phase 3 trials for ORIC-944 and enozertinib (ORIC-114) in 2026."

New P3 trial • Solid Tumor

ORIC Pharmaceuticals Announces $125 Million Private Placement Financing (GlobeNewswire) - "ORIC Pharmaceuticals...announced that it has agreed to sell approximately 19.2 million shares of its common stock (or pre-funded warrants in lieu thereof) to a select group of institutional and accredited healthcare specialist investors in a private placement, at a price per share of $6.50 (or $6.4999 per pre-funded warrant)....ORIC intends to use the net proceeds from the proposed financing to fund research and development of its clinical-stage product candidates and research programs and for working capital and general corporate purposes. The proceeds from this financing, combined with current cash, cash equivalents and marketable securities, is expected to be sufficient to fund the current operating plan into the second half of 2027 and through the anticipated primary endpoint readout from the first ORIC-944 Phase 3 registrational trial in prostate cancer."

Financing • Castration-Resistant Prostate Cancer

ORIC Pharmaceuticals Announces Potentially Best-In-Class Preliminary Efficacy and Safety Data from Ongoing Phase 1b Trial of ORIC-944 in Combination with AR Inhibitors for the Treatment of Patients with mCRPC (GlobeNewswire) - P1/1b | N=250 | NCT05413421 | Sponsor: ORIC Pharmaceuticals | "Data include 17 patients with mCRPC previously treated with a median of three lines of prior therapy, including abiraterone, up to one prior line of chemotherapy....59% of patients (10/17) achieved a PSA50 response and nearly all patients with a PSA50 response were confirmed one month later, for a confirmed PSA50 response rate of 47% (8/17)....24% of patients (4/17) achieved a PSA90 response, all of which were subsequently confirmed....Following completion of the Phase 1b dose exploration portion of the trial expected in mid-2025, the company plans to evaluate two candidate RP2Ds for each combination in the dose optimization portion of the trial in 2H 2025. Data from the dose optimization portion of the trial will inform the choice of ORIC-944 dose...in the first global Phase 3 registrational trial in mCRPC that the company expects to initiate in 1H 2026."

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

ORIC Pharmaceuticals to Present Initial Data from Phase 1b Trial of ORIC-944 in Combination with Androgen Receptor Inhibitors in Patients with mCRPC (GlobeNewswire) - "ORIC Pharmaceuticals, Inc...today announced that the company will present initial data from the Phase 1b trial of ORIC-944 in combination with androgen receptor inhibitors in patients with metastatic castration resistant prostate cancer (mCRPC) in a conference call and webcast on Wednesday, May 28, 2025, at 4:30 p.m. ET."

P1 data • Castration-Resistant Prostate Cancer

ORIC Pharmaceuticals Reports First Quarter 2025 Financial Results and Operational Updates (GlobeNewswire) - "Announced...plans to initiate first Phase 3 registrational trial for ORIC-944 in mCRPC in 1H 2026....ORIC anticipates the following upcoming milestones: ORIC-944 (mCRPC): (i) 1H 2025: Combination dose escalation data with AR inhibitors(s); (ii) 2H 2025: Updated combination dose escalation data with AR inhibitors(s); (iii) 4Q 2025 / 1Q 2026: Combination dose optimization data with AR inhibitor(s)."

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

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 (GlobeNewswire) - "ORIC Pharmaceuticals...announced the presentation of a poster at the 2025 American Association for Cancer Research (AACR) Annual Meeting, highlighting preclinical data on ORIC-944....ORIC-944 increased progression-free survival (PFS) when combined with ARPIs in both castration-sensitive and castration-resistant prostate cancer models....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."

Preclinical • Castration-Resistant Prostate Cancer

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

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 Announces ORIC-944 Preclinical Presentation at the 2025 American Association for Cancer Research (AACR) Annual Meeting (GlobeNewswire) - "ORIC Pharmaceuticals...announced that a preclinical abstract highlighting the potential of ORIC-944, a potent and selective allosteric inhibitor of PRC2 to treat prostate cancer, has been accepted for poster presentation at the 2025 American Association for Cancer Research (AACR) Annual Meeting..."

Preclinical • Prostate Cancer

ORIC-944-01: Study of ORIC-944 in Patients with Metastatic Prostate Cancer (clinicaltrials.gov) - P1 | N=250 | Recruiting | Sponsor: ORIC Pharmaceuticals | Trial primary completion date: Dec 2024 ➔ Dec 2025

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

ORIC Pharmaceuticals Announces Focused Registrational Clinical Development Plans for Lead Programs, Extended Cash Runway, and Updated Corporate Milestones (GlobeNewswire) - "ORIC-944:...Given the recently reported encouraging early safety and efficacy data from an ongoing dose escalation trial for ORIC-944 in combination with apalutamide in patients with metastatic castration resistant prostate cancer (mCRPC) and favorable enrollment trends, ORIC now expects to report dose escalation data of ORIC-944 both in combination with apalutamide and in combination with darolutamide in 1H 2025, followed by an additional update in 2H 2025. Expected timing for the previously communicated milestone of ORIC-944 dose optimization data in combination with AR inhibitor(s) has been accelerated/narrowed to 4Q25 or 1Q26 (previously 4Q25 or 1H 2026). ORIC expects to initiate its first Phase 3 trial for ORIC-944 in mCRPC in 1H 2026."

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

ORIC Pharmaceuticals Reports Fourth Quarter and Full Year 2024 Financial Results and Operational Updates (GlobeNewswire) - "ORIC anticipates the following upcoming data milestones: (1) ORIC-114 (NSCLC): (i) 1H 2025: 2L EGFR exon 20 and 2L+ HER2 exon 20; (ii) 2H 2025: 2L+ EGFR atypical; (iii) 1H 2026: 1L EGFR exon 20; (iv) Mid-2026: 1L EGFR exon 20 combination with SC amivantamab and 1L EGFR atypical; (2) ORIC-944 (mCRPC): 4Q 2025 / 1H 2026: Combination with AR inhibitors."

P1 data • P1/2 data • Castration-Resistant Prostate Cancer • Non Small Cell Lung Cancer

ORIC Pharmaceuticals Provides…Anticipated Upcoming Milestones (GlobeNewswire) - "These accomplishments position us well for 2025 and beyond, with seven anticipated data readouts over the next 18 months as we advance toward potentially initiating registrational studies for ORIC-114 in the second half of 2025 and for ORIC-944 in early 2026."

New trial • Oncology

ORIC Pharmaceuticals Provides...Anticipated Upcoming Milestones (GlobeNewswire) - "ORIC anticipates the following upcoming data milestones: ORIC-944 (mCRPC): 4Q 2025 / 1H 2026: Combination with AR inhibitors."

P1 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer