Arcus Biosciences (RCUS) Status Update summary

Updated clinical data and efficacy

• Phase 1b ARC-20 trial data for casdatifan in clear cell RCC show confirmed ORRs of 32–33% and disease control rates of 85–86% across key dose cohorts, outperforming belzutifan benchmarks on every efficacy measure.

• Median PFS reached 9.7 months in the 50 mg BID cohort and was not reached for 50 mg QD and 100 mg QD cohorts, both exceeding the 5.6 months seen with belzutifan.

• Casdatifan demonstrated rapid and durable responses, with most patients remaining on therapy and only two confirmed responders discontinuing due to progression.

• Casdatifan maintains a safety profile comparable to belzutifan, with manageable rates of anemia and hypoxia and low discontinuation due to adverse events.

• Pharmacodynamic data show sustained EPO suppression with casdatifan, supporting its differentiated efficacy profile.

Strategic and financial updates

• $150 million financing announced, including Gilead participation, to fund casdatifan development through Phase III PEAK-1 trial data readout.

• Casdatifan rights are now fully owned, providing strategic flexibility and the ability to independently pursue late-stage development.

• Collaboration with AstraZeneca enables resource-efficient pursuit of first-line RCC settings while retaining casdatifan rights.

• Approximately $1.1 billion in cash and investments as of September 30, 2024, supports aggressive development plans into mid-2027.

• R&D spending is shifting from domvanalimab to casdatifan as TIGIT program costs decline.

Development and commercialization plans

• PEAK-1 Phase III trial will evaluate casdatifan plus cabozantinib versus cabozantinib alone in second-line RCC; trial initiation is imminent and set for Q2 2025.

• AstraZeneca will initiate a Phase 1b trial of casdatifan plus volrustomig in IO-naive first-line RCC as part of the EVOLVE platform in 2025.

• Additional ARC-20 cohorts will explore casdatifan monotherapy in first-line favorable risk patients and in those who have received anti-PD-1 but not TKI.

• Commercial strategy focuses on displacing current standards, leveraging casdatifan's efficacy and tolerability, and offering once-daily tablet formulations.

• Peak sales opportunity for initial indications estimated at $5 billion or more, with potential to expand as HIF-2α inhibition becomes standard of care.