Summary of ORIC Pharmaceuticals Conference Call Company Overview - **Company**: ORIC Pharmaceuticals (NasdaqGS:ORIC) - **Focus**: Development of ORIC-114 for non-small cell lung cancer (NSCLC) patients with EGFR mutations Key Industry Insights - **Target Population**: Patients with EGFR exon 20 and EGFR PACC mutations, which occur annually in approximately 9,000 patients in the U.S. alone [6] - **Market Opportunity**: There is currently one FDA-approved therapy for first-line EGFR exon 20 and none for EGFR PACC mutation, indicating a significant unmet need in these populations [6] Core Findings from ORIC-114 Program Update - **Clinical Data**: ORIC-114 has shown highly competitive response rates in both pre-treated and front-line settings for EGFR exon 20 and EGFR PACC mutations [42] - **CNS Activity**: ORIC-114 demonstrates profound CNS activity, critical due to the high prevalence of brain metastases in these populations [5][42] - **Safety Profile**: The drug has a lack of significant off-target toxicities, such as cardiac, hepatic, and hematological liabilities, which are common with competitor inhibitors [5][42] Clinical Trial Highlights - **Phase 1b Study**: Conducted at 39 major academic centers across 10 countries, enrolling over 300 patients [16] - **Preferred Dose**: 80 mg once daily has been selected as the preferred dose for future development based on safety and efficacy observations [5][42] - **Efficacy Results**: - **Second-line Cohort**: 45% confirmed objective response rate (ORR) at 80 mg, with a 100% disease control rate [21] - **First-line Cohort**: 67% ORR with a 93% disease control rate, demonstrating strong efficacy even in patients with brain metastases [26] - **CNS-specific Responses**: 100% intracranial ORR in patients with measurable CNS disease [28] Important Considerations - **Patient Enrollment**: Unlike competitors, ORIC allowed enrollment of patients with active brain metastases from the beginning of the trial, reflecting confidence in ORIC-114's CNS penetrance [59] - **Regulatory Insights**: The FDA prefers to see CNS activity demonstrated in patients with active and measurable brain metastases, which ORIC-114 has achieved [62] - **Future Development**: Plans to continue enrollment and long-term follow-up in frontline populations, with the next update expected in mid-2026 ahead of potential phase 3 trials [42] Conclusion - ORIC-114 is positioned as a potential best-in-class treatment for patients with EGFR-mutated NSCLC, with strong clinical data supporting its efficacy and safety profile, particularly in addressing CNS metastases [42][57]