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]

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 only one FDA-approved therapy for first-line EGFR exon 20 mutations and none for EGFR PACC mutations, indicating a significant unmet need in the market [6] Core Findings from the Conference Call 1. **Clinical Data Presentation**: 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] 2. **CNS Activity**: ORIC-114 demonstrates profound CNS activity, which is critical due to the high prevalence of brain metastases in these populations [5][8] 3. **Safety Profile**: ORIC-114 has a favorable safety profile with a lack of significant off-target toxicities, such as cardiac, hepatic, and hematological issues commonly seen with competitor drugs [5][18] 4. **Preferred Dose**: The preferred dose for future development is 80 milligrams once daily, based on clinical trial data showing better safety and efficacy compared to the 120 milligram dose [5][42] 5. **Efficacy Results**: - In the second-line cohort, the best objective response rate (ORR) was 45% with a disease control rate of 100% [21] - In the first-line cohort, the best ORR was 67% with a disease control rate of 93% [26] - For patients with CNS disease, the intracranial ORR was 100% for those with measurable lesions [28] Additional Important Insights - **Enrollment Strategy**: ORIC Pharmaceuticals allowed enrollment of patients with active brain metastases from the beginning of the trial, which is a differentiating factor compared to competitors [16][59] - **Long-term Follow-up**: The next planned update for ORIC-114 is in mid-2026, ahead of potential phase 3 registrational trials [42] - **Regulatory Considerations**: The company is confident in the FDA's acceptance of the 80 mg dose based on the robust dataset generated [50] Conclusion - ORIC-114 is positioned as a potential best-in-class treatment for patients with EGFR mutations in NSCLC, with strong clinical data supporting its efficacy and safety profile, particularly in patients with CNS involvement [39][42]