Slide 1: ARC-20 Data: Cas+Cabo
ARC-20 Data: Cas+Cabo Phase 1b Study of Casdatifan + Cabozantinib in ccRCC Data presented at ASCO 2025, June 1, 2025, based on data cutoff of March 14, 2025.
Slide 2: Forward-looking Statements/Safe Harbor
Forward-looking Statements/Safe Harbor Forward Looking Statements Safe Harbor: This presentation contains forward-looking statements about Arcus Biosciences, Inc. (“we,” “Arcus” or the “Company”) made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. All
Slide 3: Agenda
Agenda TOPIC PRESENTER(S) Dr. Terry Rosen Casdatifan Value Proposition CEO, Arcus Biosciences Dr. Richard Markus ARC-20 Cas + Cabo Cohort Data CMO, Arcus Biosciences Dr. Richard Markus Casdatifan Development Plan CMO, Arcus Biosciences Jennifer Jarrett Opportunity for Casdatifan COO, Arcus Bioscienc
Slide 4: Initial Data from the Cas + Cabo Cohort Were Presented in an Oral Presentation at ASCO 2025
Initial Data from the Cas + Cabo Cohort Were Presented in an Oral Presentation at ASCO 2025 Combination Casdatifan Plus Cabozantinib in Previously Treated Patients With Clear Cell Renal Cell Carcinoma: Results From the Expansion Cohort of the Phase 1 ARC-20 Study Toni K Choueiri, MD, FASCO1; Moshe O
Slide 5: Arcus is Capitalized to Advance its Broad Portfolio of Late-Stage Programs Through Phase 3 Readouts
Arcus is Capitalized to Advance its Broad Portfolio of Late- Stage Programs Through Phase 3 Readouts CASDATIFAN: POTENTIAL BEST-IN-CLASS HIF-2α INHIBITOR $1 BILLION IN CASH* Validated mechanism Funded through initial pivotal and compelling market cas + cabo Phase 3 initiation readouts for dom, queml
Slide 6: Casdatifan Value Proposition
Casdatifan Value Proposition Dr. Terry Rosen CEO, Arcus Biosciences 6 © Arcus Biosciences 2025
Slide 7: Initial Cas + Cabo Data Substantially De-Risk PEAK-1
Initial Cas + Cabo Data Substantially De-Risk PEAK-1 • The 46% ORR for cas + cabo exceeds benchmarks for either agent ROBUST EFFICACY alone1 and the Phase 2 LITESPARK-003 benchmark for belz + cabo2 • All responses to date have confirmed and all 11 responders remain RESPONSES ALREADY on treatment as
Slide 8: Two Datasets Now Demonstrate Casdatifan's Potential to be the Best-in-Class HIF-2α Inhibitor for ccRCC
Two Datasets Now Demonstrate Casdatifan's Potential to be the Best-in-Class HIF-2α Inhibitor for ccRCC 100mg Cas + 60mg cabo in IO- Cas mono in 2L+ ccRCCb experienced ccRCCa (n=24) (n=89 across 3 cohorts) cas + cabo (ARC-20) belz + cabo (LS-003)1 cas (ARC-20) belz (LS-005)2 5m follow-up 24m follow-u
Slide 9: Casdatifan has an Optimal Pharmacological Profile Relative to That of the Competitor Belzutifan
Casdatifan has an Optimal Pharmacological Profile Relative to That of the Competitor Belzutifan • Belzutifan achieves its maximal PD effect (approx. 63% EPO suppression) at 120mg, its approved dose; dose reductions to 80mg or 40mg could result in a loss of efficacy GREATER INHIBITION • Casdatifan ac
Slide 10: The HIF-2α Market is a 2-Horse Race and Cas is Poised to Become the HIF-2α Treatment of Choice in ccRCC
The HIF-2α Market is a 2-Horse Race and Cas is Poised to Become the HIF-2α Treatment of Choice in ccRCC casdatifan belzutifan1 EFFICACY & SAFETY DATA BASED ON ARC-20 (CAS) AND LITESPARK-005 (BELZ), EACH FROM MONOTHERAPY COHORTS IN “LATE-LINE” PATIENTS Primary progressive disease <20% 34% cORR (“post
Slide 11: eVOLVE-RCC02 is Targeting the 1L Setting with the First HIF-2α-Containing TKI-Free Regimen
eVOLVE-RCC02 is Targeting the 1L Setting with the First HIF-2α-Containing TKI-Free Regimen cas + volrustomig • Clinical collaboration between Arcus and (anti-CTLA-4/anti-PD-1 bispecific) AZ where both parties retain all economics / rights to their respective molecules • Utilizing a seamless • Evalua
Slide 12: Casdatifan Has the Potential to Change the Treatment Paradigm in ccRCC and Displace TKIs in Early Lines
Casdatifan Has the Potential to Change the Treatment Paradigm in ccRCC and Displace TKIs in Early Lines POTENTIAL PARADIGM SHIFT HIF-2α mono CURRENT SOC cas Watch and Wait 1L Favorable Risk anti-PD-1 + TKI HIF-2α + anti-PD-1/CTLA-4 TKI mono cas +volrustomig anti-PD-1 + anti-CTLA-4 1L all-comers HIF-
Slide 13: ARC-20 Cas + Cabo Cohort
ARC-20 Cas + Cabo Cohort Dr. Richard Markus CMO, Arcus Biosciences 13 © Arcus Biosciences 2025
Slide 14: Data Presented at ASCO Were From the Cas + Cabo Cohort of the ARC-20 Expansion Cohorts
Data Presented at ASCO Were From the Cas + Cabo Cohort of the ARC-20 Expansion Cohorts • To date, over 200 patients have received casdatifan across all cohorts of ARC-20 DOSE ESCALATION DOSE EXPANSION Patients with advanced solid tumors N = ~30 per cohort, except cas + cabo (n=45) Casdatifan monothe
Slide 15: Patient Characteristics in the Casdatifan Plus Cabozantinib Expansion Cohort
Patient Characteristics in the Casdatifan Plus Cabozantinib Expansion Cohort CHARACTERISTIC SAFETY POPULATIONa (N = 42) Age, years, median (range) 63 (43–81) Sex, female/male, n (%) 9 (21%) / 33 (79%) ECOG PS 0/1, n (%) 29 (69%) / 13 (31%) IMDC risk score, n (%) Favorable 9 (21%) Intermediate 29 (69
Slide 16: Confirmed ORR of 46% in Patients Eligible for a Minimum of 12 Weeks Follow-Up
Confirmed ORR of 46% in Patients Eligible for a Minimum of 12 Weeks Follow-Up • To date, all responses have confirmed and all responders remain on treatment EFFICACY-EVALUABLE POPULATION (n = 24)a Follow-up, months, median (range) 5.3 (2.8–9.1) Confirmed ORRb, % (n) 46% (11) (95% CI) (26%, 67%) Best
Slide 17: Almost All Patients Achieved Tumor Reduction
Almost All Patients Achieved Tumor Reductiona,b 100 80 60 From Baseline in SLD, % Best Percent Change 40 20 0 -20 -40 -60 -80 n = 24 Complete Response Partial Response Stable Disease Progressive Disease Ongoing SLD: sum of lesion diameter; ORR: overall response rate Presented at ASCO 2025 by Toni K
Slide 18: Tumor Reduction Has Deepened Over Time and Responses Already Appear Very Durable
Tumor Reduction Has Deepened Over Time and Responses Already Appear Very Durable 40 20 From Baseline in SLD (%) 0 Percent Change -20 -40 -60 -80 0 5 10 15 20 25 30 35 40 45 Time (Weeks) Complete Response Partial Response Stable Disease Progressive Disease Treatment Ongoing ORR: overall response rate
Slide 19: Most Patients Remain on Treatment
Most Patients Remain on Treatmenta,b n = 24 0 5 10 15 20 25 30 35 40 45 Time on Treatment, Weeks Complete Response Partial Response Stable Disease Progressive Disease Ongoing Presented at ASCO 2025 by Toni K Choueiri, MD, FASCO. Data cutoff date: March 14, 2025. aAll eligible patients who received a
Slide 20: Casdatifan Dose Intensity was Consistently 95%+, Driving Efficacy and Durability
Casdatifan Dose Intensity was Consistently 95%+, Driving Efficacy and Durability CAS 100MG QD + CABO 60MG QD* CAS 100MG QD* CAS 50MG QD* CAS 50MG BID* N=27 N=29 N=31 N=33 Median duration of follow- 3.7 5.1 12.3 15.5 up, months Median Tx duration, 3.0 4.1 10.6 7.1 months Cas relative dose intensity,
Slide 21: TRAEs (Any Grade): Safety Profile was Consistent with Expectations for Cas and Cabo
TRAEs (Any Grade): Safety Profile was Consistent with Expectations for Cas and Cabo SAFETY POPULATION,a n (%) (N = 42) AE RELATED TO: casdatifan cabozantinib Any study drug Follow-up, months, median (range) 3.7 (1.1–9.1) Patients with any treatment-related AEb, n (%) 41 (98%) 39 (93%) 41 (98%) Anemi
Slide 22: Very Few Grade 3 or Higher Treatment Related AEs
Very Few Grade 3 or Higher Treatment Related AEs SAFETY POPULATION,a n (%) (N = 42) GRADE 3 OR HIGHER AE RELATED TO: casdatifan cabozantinib any study drug Patients with any treatment-related ≥ grade 3 AEb 13 (31%) 16 (38%) 20 (48%) Anemia 10 (24%) 6 (14%) 10 (24%) Hyponatremia 0 3 (7%) 3 (7%) Hypox
Slide 23: AEs Were Manageable with Dose Reductions, Leading to Very Few Discontinuations
AEs Were Manageable with Dose Reductions, Leading to Very Few Discontinuations SAFETY POPULATION,a n (%) (N = 42) LEADING TO REDUCTION IN: casdatifan cabozantinib any study drug Patients with any AE leading to dose reductionb 10 (24%) 16 (38%) 22 (52%) Fatigue 1 (2%) 5 (12%) 6 (14%) Anemia 4 (10%) 1
Slide 24: Key Takeaways from the Cas + Cabo Cohort
Key Takeaways from the Cas + Cabo Cohort ORR for cas + cabo already exceeds that of belzutifan + cabo in LITESPARK-003 Vast majority of patients experience some tumor reduction and clinical benefit While follow-up is limited, responses already appear very durable Safety profile of the combination ap
Slide 25: 8 Cohorts of ARC-20 Study Enable A Steady Cadence of Data Over the Next ~18 Months
8 Cohorts of ARC-20 Study Enable A Steady Cadence of Data Over the Next ~18 Months TIMING ARC-20 COHORTS EVENT Updated data from 50mg BID, 50mg QD (ORR, • 50mg BID PFS) Early 2025 • 50mg QD Initial data from 100mg QD tablet (ORR) • 100mg QD mono cohort Safety and initial efficacy data for the
Slide 26: Kaplan-Meier Estimates of PFS Shown at ASCO GU Bode Well for Updated PFS
PFS Kaplan-Meier Curves Shown at ASCO GU Bode Well for Updated PFS for Cas Mono Cohorts Later this Year 50mg BID Cohort (n=32) 50mg QD Cohort (n=28) Median follow-up of 15 months Median follow-up of 12 months 1.0 1.0 0.9 0.9 0.8 0.8 Kaplan-Meier Estimates of Kaplan-Meier Estimates of Progression Fre
Slide 27: Casdatifan Development Plan
Casdatifan Development Plan Dr. Richard Markus CMO, Arcus Biosciences 27 © Arcus Biosciences 2025
Slide 28: First Phase 3 Study for Cas Has a Simple Design that Utilizes the Preferred SOC in Post-IO ccRCC
First Phase 3 Study for Cas Has a Simple Design that Utilizes the Preferred SOC in Post-IO ccRCC PATIENT POPULATION: • Unresectable, locally advanced or metastatic N~700 PRIMARY ccRCC 100MG CASDATIFAN + ENDPOINT: • Measurable disease per CABOZANTINIB • PFS RECIST 1.1 KEY SECONDARY R • Have had prior
Slide 29: New Cohorts Added to ARC-20 to Evaluate New Opportunities to Displace TKIs
New Cohorts Added to ARC-20 to Evaluate New Opportunities to Displace TKIs EXPANSION COHORTS 2L+ ccRCC casdatifan mono 50mg BID capsule 2L+ ccRCC Data presented at casdatifan mono 50mg QD capsule ASCO GU 2025 Satisfies Project Optimus and confirmed 100mg QD tablet as the "going forward" 2L+ ccRCC do
Slide 30: Opportunity for Casdatifan
Opportunity for Casdatifan Jennifer Jarrett COO, Arcus Biosciences 30 © Arcus Biosciences 2025
Slide 31: Belzutifan Sales Have Grown Exponentially Despite its Usage Being Limited to Late-line ccRCC
Belzutifan Sales Have Grown Exponentially Despite its Usage Being Limited to Late-line ccRCC Monthly Belzutifan Prescriptions 2,000 • Belzutifan has rapidly established 1,800 itself as the SOC in the 3L+ ccRCC setting 1,600 1,400 − High rate of primary progression likely limits use in earlier line s
Slide 32: Initial Cas Development Plan Targets the Largest Market Segments and Could Expand Share Within These Segments
Initial Cas Development Plan Targets the Largest Market Segments and Could Expand Share Within These Segments 2024 ccRCC | US Market Share 12.6K PATIENTS 8.8K PATIENTS 100% 3% chemo 4% 10% 90% 5% 3% belz (+/- other) 80% 6% non-cabo TKI mono 70% ipi-nivo 12% avelumab + atixinib 32% Potential to repla
Slide 33: Cas + Cabo Has the Potential to Establish a New SOC in IO-Experienced ccRCC
Cas + Cabo Has the Potential to Establish a New SOC in IO- Experienced ccRCC Establishing Cas + Cabo as the HIF-2α + TKI Combination of Choice • Cabo is the preferred TKI in IO-experienced ccRCC due Cas 100mg to a perceived better safety profile and simpler titration (1 x 100mg) • Cas is the only HI
Slide 34: Avoiding Overlapping Toxicity is Key to Maintaining Patients on Therapy and Positions HIF-2α as the Ideal Backbone
Avoiding Overlapping Toxicity is Key to Maintaining Patients on Therapy and Positions HIF-2α as the Ideal Backbone Casdatifan TKIs anti-PD-1 anti-PD-1/CTLA-4 100mg coated tablet 25mg coated tablet • Anemia • Diarrhea • Diarrhea • Diarrhea • Hypoxia • Rash • Rash • Rash • Fatigue • Hepatotoxicity • H
Slide 35: Our Initial Focus Is on the IO-naive and Post-IO Settings, Both Multi-Billion Dollar Market Opportunities
Our Initial Focus Is on the IO-naive and Post-IO Settings, Both Multi-Billion Dollar Market Opportunities POTENTIAL MARKET SIZE CURRENT SOC FUTURE TREATMENT (MAJOR MARKETS1,2) CAS FUTURE DEVELOPMENT 21k patients IO-naive Anti-PD-1 + metastatic CTLA4 ~$3B New cohorts added OPPORTUNITY to ARC-20: cas
Slide 36: As Casdatifan Moves Up in the Treatment Paradigm, the U.S. Market Opportunity Will Grow Substantially
As Casdatifan Moves Up in the Treatment Paradigm, the U.S. Market Opportunity Will Grow Substantially Potential ccRCC Patients on HIF-2α Inhibitors over Time (US, Annual) TODAY 2027+ 2030+ 1L ~9K ~16mo DoT 2L ~1K ~6K ~6K ~11mo DoT 3L ~2K ~3K ~1K ~8mo DoT 3K 9K 16K TOTAL TOTAL TOTAL 1L: first-line; 2
Slide 37: Closing Remarks
Closing Remarks Dr. Terry Rosen CEO, Arcus Biosciences 37 © Arcus Biosciences 2025
Slide 38: Rapid Advancement and Expansion of the Cas Program Is Our Priority over the Next Year
Rapid Advancement and Expansion of the Cas Program Is Our Priority over the Next Year Cas is Poised to Be the HIF-2α Multiple Data Events Coming Inhibitor of Choice for RCC Over the Next ~18 Months • HIF-2α inhibitors is expected to become TIMING SETTING EVENT another SOC in the $6B+ ccRCC market*,
Slide 39: Three Phase 3 Programs Targeting Substantial Market Opportunities and Unmet Medical Need
Three Phase 3 Programs Targeting Substantial Market Opportunities and Unmet Medical Need Designed to improve upon the current standard of care PEAK PHASE 3 PATIENTS MARKET POTENTIAL INVESMENT YEAR TRIAL NAME STATUS INDICATION (MAJOR MARKETS1,2) (MAJOR MARKETS2) CAS To Begin Shortly Post-IO ccRCC 19K