Core Insights - ORIC Pharmaceuticals announced data from a Phase 1b trial of enozertinib (ORIC-114) for treating NSCLC patients with HER2 exon 20 mutations, showing a 35% overall response rate (ORR) and 100% disease control rate (DCR) in the 80 mg cohort [1][8] - The trial included patients with active brain metastases, and the safety profile was manageable with a low discontinuation rate due to treatment-related adverse events (TRAEs) [1][4] - Enrollment for the HER2 exon 20 patient population has been completed, with no further development planned, while the 80 mg dose has been selected for potential Phase 3 development based on preliminary data [6][8] Trial Design and Patient Demographics - The Phase 1b trial evaluated enozertinib in patients with locally advanced or metastatic NSCLC with HER2 exon 20 mutations, allowing for patients with untreated brain metastases [2] - As of the cutoff date, 49 patients were dosed, with 80% having received prior chemotherapy and 35% having undergone HER2 targeted therapy [3] Safety and Efficacy Analysis - Enozertinib was well tolerated, with most TRAEs being Grade 1 or 2, and only 2 patients discontinued treatment due to TRAEs [4] - Tumor responses were noted in both dosing cohorts, with deeper regressions observed in the 80 mg cohort, potentially due to fewer dose reductions [5] Next Steps and Future Development - The company plans to continue enrollment and follow-up in 1L NSCLC patients with EGFR exon 20 and other mutations, with updates expected in mid-2026 [6] - The 80 mg QD oral enozertinib has been selected for potential Phase 3 development based on the trial results [6] Conference Call and Webcast - ORIC will host a conference call and webcast on December 6, 2025, to discuss the trial results and future plans [7]

Core Insights - Enozertinib (ORIC-114) shows promising preliminary systemic activity with an 80% overall response rate (ORR) and a 100% intracranial ORR in first-line (1L) NSCLC patients with EGFR P-loop and alpha C-helix compressing (PACC) mutations [1][8] - The drug demonstrates a competitive safety profile with manageable on-target toxicity and no significant off-target toxicity, leading to a low discontinuation rate [1][5] - The company plans to continue enrollment and follow-up in 1L EGFR PACC patients, with the next update expected in mid-2026 ahead of a potential Phase 3 trial [1][9] Efficacy and Safety Data - In a Phase 1b trial, enozertinib was evaluated in patients with locally advanced or metastatic NSCLC with EGFR atypical mutations, allowing for patients with active untreated brain metastases [3] - As of the August 29, 2025 cutoff, 47 patients were dosed, with 36% confirmed ORR and 91% disease control rate (DCR) in previously treated patients with EGFR atypical mutations [4][7] - The most common treatment-related adverse events (TRAEs) were Grade 1 or 2, including diarrhea, paronychia, and stomatitis, with no treatment discontinuations due to TRAEs [5] Future Development Plans - The 80 mg once daily dose of enozertinib has been selected for potential Phase 3 development based on preliminary data [9] - The company will host a conference call and webcast on December 6, 2025, to discuss the findings and future plans [10] Company Overview - ORIC Pharmaceuticals is a clinical stage biopharmaceutical company focused on developing treatments that address mechanisms of therapeutic resistance in cancer [11] - The company is also developing ORIC-944, an allosteric inhibitor for prostate cancer, alongside enozertinib for multiple genetically defined cancers [11]

Core Insights - ORIC Pharmaceuticals, Inc. is a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance [3] - The company will participate in a fireside chat at the 8th Annual Evercore Healthcare Conference on December 3, 2025, at 11:15 a.m. ET [1] - A webcast of the fireside chat will be available on the company's investor website, with a replay accessible for 90 days post-event [2] Company Overview - ORIC Pharmaceuticals is dedicated to improving patients' lives by overcoming resistance in cancer [3] - The company's clinical stage product candidates include ORIC-944, an allosteric inhibitor targeting the polycomb repressive complex 2 (PRC2) for prostate cancer, and enozertinib (ORIC-114), a brain-penetrant inhibitor for various genetically defined cancers [3] - ORIC has offices located in South San Francisco and San Diego, California [3]

Core Insights - ORIC Pharmaceuticals, Inc. is set to present initial data from the Phase 1b trial of ORIC-944 in combination with androgen receptor inhibitors for metastatic castration resistant prostate cancer on May 28, 2025 [1] Company Overview - ORIC Pharmaceuticals is a clinical stage biopharmaceutical company focused on developing treatments that address mechanisms of therapeutic resistance in cancer [4] - The company's product candidates include ORIC-944, an allosteric inhibitor of the polycomb repressive complex 2 (PRC2) for prostate cancer, and ORIC-114, which targets specific mutations in various cancers [4] Product Details - ORIC-944 has shown potential best-in-class drug properties, including a clinical half-life of approximately 20 hours and a favorable safety profile [3] - The ongoing Phase 1b trial is evaluating ORIC-944 in combination with ERLEADA (apalutamide) and NUBEQA (darolutamide) for metastatic castration resistant prostate cancer [3]