Core Insights - ORIC Pharmaceuticals announced promising data from a Phase 1b trial of enozertinib (ORIC-114) for treating NSCLC patients with EGFR exon 20 mutations, showing a 67% overall response rate (ORR) and 100% intracranial ORR in treatment-naïve patients with active brain metastases [1][2][16] - The drug demonstrated a 45% ORR in previously treated (2L) patients, surpassing competitor benchmarks, and exhibited a competitive safety profile with manageable on-target toxicity [1][4][5] - The company plans to continue enrollment and follow-up in 1L patients at a selected dose of 80 mg once daily, with the next update expected in mid-2026 ahead of a potential Phase 3 trial [1][12] Trial Design and Patient Demographics - The Phase 1b trial is evaluating enozertinib in patients with locally advanced or metastatic NSCLC with EGFR exon 20 mutations, allowing enrollment of patients with active untreated brain metastases [3] - As of August 29, 2025, 45 2L patients were dosed, with 38% having brain metastases at baseline [4] - In the 1L cohort, 33 patients were dosed, with 39% presenting with brain metastases [7] Safety and Efficacy Analysis - Preliminary safety analysis indicated that enozertinib was well tolerated, with most treatment-related adverse events (TRAEs) being Grade 1 or 2, and only a small number of patients discontinuing treatment due to TRAEs [5][9] - In the 80 mg cohort, 67% of responders remained on treatment at a median follow-up of over 30 weeks, while in the 120 mg cohort, 80% of patients underwent early dose reductions due to TRAEs [8][10][16] - The drug showed strong systemic and CNS antitumor activity, with 100% disease control rate (DCR) in patients with brain metastases [8][16] Next Steps and Future Plans - The company has selected 80 mg QD oral enozertinib as the dose for potential Phase 3 development, with ongoing enrollment and follow-up in 1L EGFR exon 20 patients [12] - A conference call and webcast is scheduled for December 6, 2025, to discuss the trial results and future plans [13]

Core Insights - ORIC Pharmaceuticals reported promising clinical efficacy and safety data from the ongoing Phase 1b trial of ORIC-944 in combination with AR inhibitors for treating metastatic castration-resistant prostate cancer (mCRPC) [1][5] - The company strengthened its cash position with $244 million in gross proceeds from a $125 million private placement and $119 million from at-the-market (ATM) issuances, extending its cash runway into the second half of 2028 [1][9] - ORIC has revised its operating plan to focus on advancing its lead clinical programs, ORIC-944 and enozertinib, while significantly reducing investment in discovery research [2][9] Financial Highlights - As of June 30, 2025, ORIC reported cash, cash equivalents, and investments totaling $327.7 million, which increased to $436.4 million after additional fundraising [9][15] - Research and development (R&D) expenses for Q2 2025 were $30.5 million, up from $28.9 million in Q2 2024, reflecting higher personnel costs and advancement of enozertinib [9][15] - General and administrative (G&A) expenses for Q2 2025 were $8.5 million, compared to $7.1 million in Q2 2024, primarily due to increased personnel costs and professional services [9][15] Clinical Development Updates - ORIC-944 demonstrated a 59% PSA50 response rate and a 24% PSA90 response rate in patients with mCRPC, indicating its potential as a best-in-class PRC2 inhibitor [5] - Enozertinib continues to enroll patients in a Phase 1b trial targeting advanced non-small cell lung cancer (NSCLC) with specific EGFR and HER2 mutations [4][10] - The company anticipates initiating registrational trials for ORIC-944 and enozertinib in 2026, with key data milestones expected in late 2025 and mid-2026 [7][9]