Summary of ORIC Pharmaceuticals Conference Call Company Overview - **Company Name**: ORIC Pharmaceuticals - **Ticker**: NasdaqGS:ORIC - **Focus**: Oncology, specifically small molecule drug development for solid tumors, with a focus on lung cancer and prostate cancer [3][4] Key Programs ORIC-944 (Prostate Cancer) - **Mechanism**: Small molecule inhibitor of PRC2, targeting the EED subunit, in combination with androgen receptor (AR) inhibitors [4][8] - **Current Status**: In dose optimization, aiming to start Phase 3 studies next year [4][26] - **Efficacy**: Early data shows a confirmed PSA 50 response rate of 47% and a PSA 90 response rate of 24%, outperforming Pfizer's data [20][21] - **Safety Profile**: ORIC-944 shows a differentiated safety profile with less toxicity compared to Pfizer's Mezigdomide, particularly in terms of hematologic and gastrointestinal toxicity [22][23] - **Half-Life**: ORIC-944 has a 20-hour half-life, allowing for once-daily dosing, which is expected to reduce Cmax-related toxicities [15][16] ORIC-114 (Lung Cancer) - **Focus**: Developed for non-small cell lung cancer, targeting multiple genetic mutations including EGFR exon 20 and HER2 exon 20 [49][50] - **Differentiation**: Emphasizes safety, tolerability, and CNS activity, which is crucial as many lung cancer patients present with brain metastases [52][53] - **Upcoming Data**: Substantial data readouts expected in the second half of this year and early next year, with a focus on three cohorts of patients [55][56] Financial Position - **Funding**: The company is well-funded, with a cash runway extending past the Phase 3 data readouts for both programs [4][72] - **Market Opportunity**: The prostate cancer market is significant, with an estimated $3.5 billion treatable market in the U.S. for the targeted populations [47][48] Competitive Landscape - **Comparison with Pfizer**: ORIC-944 is positioned as a potential competitor to Pfizer's Mezigdomide, with expectations of capturing 35% to 40% market share as a second entrant [46][48] - **AR Inhibitors**: ORIC has supply agreements with apalutamide and darolutamide, both of which are viewed as having similar efficacy but better safety profiles compared to enzalutamide [39][40] Upcoming Milestones - **Data Updates**: Incremental updates expected in the second half of this year, with a more substantial update in Q1 2026 [28][30] - **Phase 3 Study**: Plans to initiate a pivotal study for ORIC-944 in the first half of next year, with a focus on the CRPC setting [34][66] Conclusion - **Investor Attention**: ORIC Pharmaceuticals is positioned for significant data releases and has a strong financial foundation, making it a company to watch in the oncology space over the next 6 to 12 months [75][76]

Summary of ORIC Pharmaceuticals Conference Call Company Overview - **Company**: ORIC Pharmaceuticals - **Focus**: Development of small molecule drugs targeting resistance in oncology, specifically for solid tumors like prostate and lung cancer Key Programs - **Lead Programs**: - **ORIC-944**: A small molecule PRC2 inhibitor for castration-resistant prostate cancer (CRPC), currently in dose optimization and expected to enter phase three studies next year - **ORIC-114**: A small molecule TKI targeting non-small cell lung cancer (NSCLC) with brain metastases, also in dose optimization Core Insights - **Market Potential**: The combined market for AR inhibitors in prostate cancer is approximately $7 billion in the U.S. alone, with each patient population (post-abiraterone and post-ARPI) representing about $3.5 billion [doc id='36'][doc id='37'] - **Comparison with Competitors**: ORIC-944 has a 20-hour half-life and better drug properties compared to Pfizer's Mavrimodastat, which has a 4-5 hour half-life. ORIC-944 shows higher PSA response rates (47% confirmed PSA 50 rate vs. Pfizer's 34%) and lower toxicity [doc id='10'][doc id='13'][doc id='14'] - **Safety Profile**: ORIC-944 exhibits a lower incidence and severity of toxicities compared to Pfizer's drug, with no reported alopecia, which is significant for prostate cancer patients [doc id='15'] Clinical Data and Updates - **Phase One Data**: ORIC-944 showed promising early efficacy with a small sample size (n=17), indicating potential for longer-term durability [doc id='12'][doc id='13'] - **Upcoming Updates**: The second half of the year will provide incremental updates on dose selection and rationale for ORIC-944, with a more substantial update expected in Q1 2026 [doc id='24'][doc id='30'] Competitive Landscape - **CNS Activity**: ORIC-114 is positioned as a CNS-active agent, which is crucial as many lung cancer patients present with brain metastases. This could lead to longer progression-free survival [doc id='42'][doc id='43'] - **Market Dynamics**: The AR inhibitor market is large, with significant sales from existing drugs. ORIC aims to capture market share through better efficacy and safety profiles [doc id='36'][doc id='39'] Financial Position - **Cash Runway**: ORIC ended Q2 with $436 million in cash, providing a runway into the second half of 2028, which covers the phase three readouts for both ORIC-944 and ORIC-114 [doc id='56'] Strategic Considerations - **Partnership Opportunities**: ORIC is open to various forms of partnerships, including drug supply agreements and potential collaborations for broader development, especially for ORIC-944 in CSPC [doc id='54'] Conclusion - ORIC Pharmaceuticals is advancing its lead programs with promising clinical data and a strong financial position, positioning itself competitively in the oncology market, particularly in prostate and lung cancer treatments. The company is focused on optimizing its drug candidates while preparing for upcoming phase three studies.

Summary of Oric Pharmaceuticals (ORIC) 2025 Conference Call Company Overview - **Company Name**: Oric Pharmaceuticals (ORIC) - **Focus**: Development of small molecule drugs targeting solid tumors, specifically in lung cancer, prostate cancer, and breast cancer [4][5] Key Programs - **ORIC-944**: A PRC2 inhibitor for prostate cancer, currently in combination studies with two androgen receptor inhibitors (apalutamide and darolutamide) [5][6] - **ORIC-114**: A brain-penetrant inhibitor targeting lung cancer populations, including EGFR exon 20, EGFR atypicals, and HER2 exon 20 [6] Clinical Data and Comparisons - **Prostate Cancer Data**: - ORIC-944 showed a confirmed PSA 50 response rate of 47% compared to Pfizer's mevremetostat at 34% [10][13] - Confirmed PSA 90 response rate for ORIC-944 was 24% versus Pfizer's 12% [11][13] - Safety profile of ORIC-944 demonstrated lower rates of gastrointestinal toxicity compared to Pfizer's drug [14][15] Safety and Efficacy - **Toxicity Comparison**: ORIC-944 exhibited significantly lower rates of GI toxicity and anemia compared to Pfizer's data, which reported high rates of diarrhea and dysgeusia [14][15] - **Dosing Strategy**: ORIC-944 has a longer half-life allowing for once-daily dosing, while Pfizer's drug requires twice-daily dosing [26][27] Future Development Plans - **Phase III Study**: Planned to start in the first half of 2026, focusing on both post-abiraterone and post-AR inhibitor populations [33][44] - **Data Updates**: Two additional data updates expected later in 2025, focusing on dose escalation and optimization [34][36] Market Position and Strategy - **Competitive Landscape**: ORIC aims to close the timeline gap with Pfizer, emphasizing that being a second entrant in a large market can still yield significant commercial opportunities [60][61] - **Partnerships**: Strong relationships with Janssen and Bayer for drug supply and insights into clinical development [51][52] Financial Position - **Cash Position**: As of March, ORIC reported a pro forma cash position of $349 million, providing a runway into the second half of 2027 [73] Additional Insights - **ctDNA as a Biomarker**: ORIC is exploring ctDNA as a potential better marker for long-term durability compared to PSA activity [40][41] - **Focus on Frontline Opportunities**: ORIC is prioritizing frontline strategies for ORIC-114, aiming for robust data in competitive populations [63][64] Conclusion - ORIC Pharmaceuticals is positioned to advance its clinical programs with promising early data, a strong financial position, and strategic partnerships, while navigating a competitive landscape in oncology.

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.

Core Insights - ORIC Pharmaceuticals announced promising preliminary efficacy and safety data for ORIC-944 in combination with androgen receptor inhibitors in patients with metastatic castration-resistant prostate cancer (mCRPC) [1][3] - The company reported a 59% PSA50 response rate and a 24% PSA90 response rate in the ongoing Phase 1b trial, indicating substantial clinical activity [1][6] - A concurrent financing of $125 million is expected to extend the company's cash runway into the second half of 2027, supporting further development of ORIC-944 [10] Efficacy Data - The Phase 1b trial showed a confirmed PSA50 response rate of 47% and a PSA90 response rate of 24%, with responses observed across all dose levels of ORIC-944 [1][6][7] - The majority of patients are still ongoing with treatment, with several approaching one year or more on therapy [1][7] Safety Profile - ORIC-944 demonstrated a favorable safety profile, with most adverse events classified as Grade 1 or 2, primarily mild to moderate gastrointestinal issues [2][8] - Diarrhea was the most common treatment-related adverse event, occurring in 53% of patients, with only one Grade 3 event reported [8] Trial Design and Next Steps - The ongoing Phase 1b trial is designed to explore different doses of ORIC-944 in combination with apalutamide and darolutamide, with the primary objective of determining the recommended Phase 2 dose [4][9] - Following the completion of the dose exploration phase, the company plans to evaluate candidate doses for optimization in the second half of 2025, leading to a global Phase 3 trial expected to start in the first half of 2026 [9] Corporate Update - The $125 million financing is anticipated to close on May 29, 2025, and will support the company's operations through the primary endpoint readout of the first Phase 3 trial [10]

Core Insights - ORIC Pharmaceuticals, Inc. presented preclinical data on ORIC-944, a selective allosteric inhibitor of PRC2, at the 2025 AACR Annual Meeting, showing improved progression-free survival (PFS) when combined with androgen receptor pathway inhibitors (ARPIs) in prostate cancer models [1][2][6] Group 1: ORIC-944 Overview - ORIC-944 is characterized as a potent and selective allosteric inhibitor of PRC2, demonstrating best-in-class properties in preclinical studies, including favorable pharmacokinetics and a clinical half-life of approximately 20 hours [3][6] - The drug is currently being evaluated in a Phase 1b trial in combination with ERLEADA (apalutamide) and NUBEQA (darolutamide) for prostate cancer [3][6] Group 2: Clinical Implications - The data presented indicate that ORIC-944 enhances PFS in both castration-sensitive and castration-resistant prostate cancer models, suggesting its potential to reverse the evolution of prostate cancer [2][6] - ORIC-944 demonstrated transcriptional and antitumor synergy with ARPIs, reinforcing its role in blocking prostate tumor adaptation and restoring luminal features [6] Group 3: Company Background - ORIC Pharmaceuticals is focused on developing treatments that address mechanisms of therapeutic resistance in cancer, with ORIC-944 and ORIC-114 as key product candidates [4]