Summary of ORIC Pharmaceuticals FY Conference Call Company Overview - **Company Name**: ORIC Pharmaceuticals (NasdaqGS:ORIC) - **Industry**: Oncology - **Mission**: Overcoming Resistance in Cancer, focusing on developing therapies for cancer patients [2][3] Key Pipeline Assets - **Rinsey-Metastat**: A PRC2 inhibitor for prostate cancer, expected to have a phase three data readout in the second half of 2027 [3][11] - **Enosertinib**: A brain-penetrant TKI for lung cancer, targeting EGFR exon 20 and PAC mutations, with a phase three dose selected [5][35] Financial Position - **Cash Runway**: Well-funded with cash runway extending into the second half of 2028, allowing for continued development of both pipeline assets [3][11] Clinical Development Highlights Rinsey-Metastat - **Combination Studies**: Being developed in combination with apalutamide (J&J) and daralutamide (Bayer) [4][7] - **Safety Profile**: Demonstrated a differentiated safety profile compared to competitors, which is crucial for long-term dosing [8][29] - **Efficacy Data**: - Confirmed PSA response rates of 40% for PSA 50 and 20% for PSA 90, significantly higher than expected rates for AR inhibitors alone [24] - ctDNA clearance rate of 59%, indicating strong activity [26][27] Enosertinib - **CNS Activity**: Achieved a 100% intracranial objective response rate (ORR) in patients with measurable disease, highlighting its potential in treating CNS metastases [10][33] - **Patient Enrollment**: Allowed patients with active untreated CNS metastases, which is uncommon in competitor studies [34] Competitive Landscape - **Main Competitor**: Pfizer's mevrometostat, which has shown promising results but comes with higher toxicity [6][28] - **Market Opportunity**: The prostate cancer market is substantial, with AR inhibitors generating $11 billion in global revenue [16][17] Future Milestones - **Phase 3 Studies**: Expected to initiate one or two phase 3 studies within the year for both Rinsey-Metastat and Enosertinib [46] - **Data Releases**: Anticipated data from dose optimization studies in Q1 2026, focusing on efficacy and safety [50] Additional Insights - **Long-term Durability**: The combination of Rinsey-Metastat with AR inhibitors aims to extend the durability of treatment, addressing a significant unmet need in prostate cancer [17][19] - **Broader Applications**: Potential future development of PRC2 inhibitors in other cancers, including lung and breast cancer [30] Conclusion - ORIC Pharmaceuticals is positioned to make significant advancements in oncology with its innovative pipeline, particularly in addressing unmet needs in prostate and lung cancer, while maintaining a strong financial position to support its development efforts [46]

Summary of Oric Pharmaceuticals (ORIC) Update / Briefing May 28, 2025 Company Overview - **Company**: Oric Pharmaceuticals (ORIC) - **Focus**: Development of ORIC-944, a potential best-in-class PRC2 inhibitor for metastatic castration-resistant prostate cancer (mCRPC) in combination with androgen receptor inhibitors (ARIs) like apalutamide and darolutamide [3][6][10] Key Points and Arguments Clinical Pipeline and Study Updates - ORIC is advancing two key programs with multiple data readouts expected in 2025 and early 2026, aiming for Phase 3 trials initiation in 2026 [6][10] - The ongoing Phase 1b study of ORIC-944 is focused on its combination with epalutamide and darolutamide in mCRPC patients [3][6] - Initial data indicates a favorable safety and activity profile for ORIC-944, with a focus on overcoming resistance in prostate cancer [8][10] Mechanism and Rationale - ORIC-944 is designed to address limitations of first-generation PRC2 inhibitors, showing improved potency and tolerability [7][13] - The combination of PRC2 inhibitors with ARIs is supported by biological rationale to delay or overcome resistance in prostate cancer [7][15] - Preclinical data shows ORIC-944 enhances AR signaling and luminal cell state markers, increasing sensitivity to AR inhibition [15][19] Efficacy and Safety Data - In the study, 17 patients with mCRPC showed a 59% PSA50 response rate and a 24% PSA90 response rate, with responses confirmed one month later [29][30] - The safety profile of ORIC-944 was generally well tolerated, with most adverse events being grade one or two, primarily mild gastrointestinal issues [31][32] - The combination therapy demonstrated a wide therapeutic window, with doses as low as 400 mg showing efficacy [30][31] Market Opportunity - The global market for AR inhibitors reached approximately $11 billion, with significant potential for PRC2 inhibitors to enhance treatment durability and outcomes [38][42] - ORIC-944 targets an addressable market opportunity of over $7 billion annually in the U.S. for mCRPC patients treated with AR inhibitors [42] Expansion Opportunities - ORIC-944 may have potential applications in other cancers, including breast and colorectal cancers, due to shared reliance on PRC2 mechanisms [44][48] - Future studies will explore ORIC-944 in earlier stages of prostate cancer and in combination with other therapies [48] Additional Important Content - The company completed a $125 million PIPE financing, extending its cash runway into the second half of 2027 [50] - The competitive landscape includes comparisons with Pfizer's mebrametostat, with ORIC-944 showing promising early efficacy and safety data [85][88] - The decision on which AR inhibitor to combine with for Phase 3 trials will be based on overall data and strategic considerations [79][80] This summary encapsulates the critical insights from the conference call, highlighting the company's strategic direction, clinical advancements, and market potential for ORIC-944 in prostate cancer treatment.