Arcus Biosciences (RCUS) H.C. Wainwright 27th Annual Global Investment Conference summary

Key pipeline programs and recent progress

• Three programs with five phase 3 studies are underway, enabled by significant financing from partners including Gilead, AstraZeneca, and Taiho.

• Castatinopathy, a next-generation HIF2α inhibitor, has shown promising data in multiple medical meetings, with further data presentations scheduled.

• The PEAK1 phase 3 study evaluates castatinopathy plus cabozantinib versus cabozantinib alone in IO-experienced clear cell RCC, targeting a $2 billion market.

• The Evolve phase 1b/3 study, in collaboration with AstraZeneca, assesses castatinopathy plus volrue in first-line clear cell RCC, aiming for a $3 billion market.

• Approximately $900 million in cash reserves support ongoing and future clinical programs.

Differentiation and efficacy of castatinopathy

• Castatinopathy achieves equivalent biomarker suppression at a much lower dose than belzutifan, suggesting stronger target engagement.

• Demonstrates a superior PK/PD profile, allowing higher drug exposure and potentially greater efficacy compared to belzutifan.

• Monotherapy cohorts show a 31% confirmed response rate and median PFS of 9.7 months, outperforming belzutifan's 22% response rate and 5.6-month PFS.

Combination strategies and trial design

• Castatinopathy is combined with cabozantinib, the preferred TKI in second-line RCC, due to non-overlapping safety profiles and physician familiarity.

• The PEAK1 phase 3 trial is a randomized, placebo-controlled study with PFS as the primary endpoint and OS as a key secondary endpoint.

• PEAK1 differs from Merck’s LIGHTSPARK-11 by focusing statistical power on PFS and using the same TKI in both arms, reducing design risk.