Summary of Arcus Biosciences FY Conference Call Company Overview - **Company**: Arcus Biosciences (NYSE: RCUS) - **Focus**: Development of innovative cancer therapies, particularly in the area of HIF-2 inhibitors and anti-TIGIT therapies Key Points 1. Strategic Focus on Casdatifan - Casdatifan is highlighted as a primary focus due to its ownership and strategic optionality - The drug is considered highly de-risked based on internal data and validation from belzutifan, which has a current run rate of $700 million despite being sold in late lines only - Casdatifan shows superior data compared to belzutifan across multiple efficacy measures, including progression-free survival (PFS) which is more than double that of belzutifan [2][3] 2. Upcoming Data and Studies - Anticipation for more data in 2026, particularly regarding front-line strategies and phase 3 studies - STAR-221, a phase 3 study correlating with EDGE-Gastric, is expected to read out in 2026, with 1,050 patients fully enrolled by June 2024 [5][6] - STAR-121, focusing on PD-L1 non-small cell lung cancer, will also be fully enrolled by the end of this year with 1,000 patients [6] 3. Anti-TIGIT Developments - Arcus has demonstrated differentiation between Fc-silent and Fc-enabled anti-TIGIT molecules, with promising data from the EDGE-Gastric study showing overall survival (OS) exceeding two years compared to approximately 13 months for standard treatments [4][5] - The company is optimistic about the STAR-221 results influencing the sentiment around STAR-121 [6] 4. Combination Therapies - Casdatifan is expected to provide meaningful benefits when combined with other therapies, such as cabozantinib (CABL) and anti-PD-1 agents, showing higher overall response rates compared to belzutifan combinations [9][10][11] - The combination of CAST (casdatifan) with CABL has shown a response rate of over 40% compared to 31% for belzutifan plus CABL [11] 5. Tolerability and Patient Management - CABL is favored by clinicians for its better tolerability compared to lenvatinib (Lenva), with lower incidences of common TKI-related adverse events [26][27] - The management of anemia in patients on HIF-2 therapy has been effective, with no discontinuations due to anemia reported in a cohort of 120 patients [18][19] 6. Future Directions - Arcus plans to explore additional combinations, including anti-PD-1 and bispecific therapies, to enhance treatment efficacy [30][31] - The company is focused on TKI-sparing regimens, allowing for better quality of life for patients while reserving TKIs for later stages of treatment [34] 7. Clinical Trials and Data Expectations - More mature data from the CAST plus CABL cohort is expected to be presented next year, with a focus on PFS and durability of response [21][24] - The company is also monitoring the performance of Merck's Lenva and belzutifan combinations for comparative insights [26] 8. Conclusion - Arcus Biosciences is positioned to make significant advancements in cancer treatment through its innovative therapies and strategic focus on casdatifan and anti-TIGIT developments, with several key studies and data releases anticipated in the near future [36]

Summary of Arcus Biosciences Conference Call - September 03, 2025 Company Overview - **Company**: Arcus Biosciences (RCUS) - **Focus**: Development of innovative cancer therapies, particularly in the area of HIF-2 alpha inhibitors Key Points and Arguments Product Pipeline and Clinical Trials - **Casdatafan**: - Positioned as a best-in-class HIF-2 alpha inhibitor, with compelling data from 120 patients indicating superior efficacy compared to Merck's belzutafan [6][17] - Total addressable market estimated at $10 billion [7] - Phase 3 studies initiated, including a combination with cabozantinib (cabo) and a collaboration with AstraZeneca for frontline settings [8][10] - Expected rapid enrollment due to investigator enthusiasm [7][11] - **Domzim**: - An anti-TIGIT, anti-PD-1 combination therapy, with data to be presented at ESMO [9][10] - **Quemly**: - A CD73 inhibitor in pancreatic cancer, fully enrolled ahead of schedule, with results expected in the next 12-18 months [12][97] Competitive Landscape - **Comparison with Merck's Belzutafan**: - Casdatafan shows a lower rate of primary progression (15% vs. 35% for belzutafan) and better overall response rates (over 30% vs. just over 20%) [17][18] - Arcus believes their development strategy is superior, focusing on combining with cabo, which is more widely used and easier to manage than Merck's lenvatinib [22][24] Strategic Advantages - **Development Strategy**: - Arcus employs a cleaner statistical analysis plan with a single primary endpoint of progression-free survival (PFS) [30] - Two-to-one randomization in trials to enhance patient enrollment [32] - **Collaboration with AstraZeneca**: - Cost-sharing arrangement for a phase 1b/3 study combining Casdatafan with AstraZeneca's bispecific anti-PD-1/CTLA-4 [40][41] Upcoming Data and Events - **Investor Event**: - Scheduled for October 6, 2025, to present updated data on Casdatafan and other therapies [8] - **Data Readouts**: - Continuous flow of data expected from various studies, including OS data from the Edge Gastric study and the phase 3 study for upper GI cancers [10][66] Market Positioning - **TKI-Sparing Regimen**: - Arcus aims to shift the use of TKIs to later lines of therapy, enhancing patient quality of life by avoiding early toxicities associated with TKIs [49] Other Important Insights - **Safety Profile**: - Casdatafan is expected to have minimal overlapping toxicity with other treatments, which could make it a backbone agent in clear cell renal cell carcinoma (CCRCC) [60] - **Regulatory Landscape**: - No competing phase 3 studies currently exist for Casdatafan, positioning Arcus favorably in the market [35] Conclusion - Arcus Biosciences is in a transformative phase with multiple late-stage clinical trials and a strong competitive position against Merck's belzutafan. The company is focused on delivering innovative therapies with a favorable safety profile and robust efficacy data, aiming to capture significant market share in the oncology space.