Arcus Biosciences (RCUS) investor relations material

Key clinical differentiators and efficacy data

• Casdatifan demonstrates superior PK/PD profile with linear dose proportionality, enabling stronger target engagement compared to belzutifan, which has absorption-limited kinetics.

• Confirmed response rates for casdatifan are about 35% in 120 late-line monotherapy patients and 45% at the 100mg go-forward dose, versus just over 20% for belzutifan.

• Median PFS for casdatifan is 12.2 months (all patients) and over 15 months (100mg cohort), compared to 5.6 months for belzutifan.

• Biomarker data show deeper and more durable erythropoietin suppression with casdatifan, correlating with improved efficacy.

• Casdatifan’s efficacy is consistent across PK/PD, ORR, PFS, and biomarker data, highlighting a distinct profile from belzutifan.

Durability, safety, and resistance profile

• HIF-2α inhibition leads to prolonged disease control, with many patients experiencing tumor reduction and durable responses beyond two years.

• The mechanism is non-toxic, with manageable on-target AEs such as anemia and rare hypoxia, both related to erythropoietin suppression.

• Durability is enhanced by the therapy’s safety, allowing patients to remain on treatment longer and benefit from immune system recovery.

• No significant mechanism for resistance has been observed, with only rare mutations reported.

• HIF-2 inhibitors are expected to be usable in every line of therapy for RCC, similar to bevacizumab in colorectal cancer.

Safety and adverse event management

• Anemia and hypoxia rates for casdatifan are nearly identical to belzutifan, with no evidence of increased toxicity despite higher potency.

• Clinicians are improving at managing these toxicities, and rates may decrease over time as experience grows.

• No anticipated difference in AE rates between casdatifan and belzutifan in phase III studies.