ORIC® Pharmaceuticals Presents Potential Best-in-Class Profile for Enozertinib with Robust Systemic and CNS Activity in 1L and Previously Treated NSCLC Patients with EGFR Atypical Mutations at the ESMO Asia Congress 2025

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]