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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.
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© Arcus Biosciences 2025 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 statements regarding events or results to occur in the future contained in this presentation are forward-looking statements, including statements about: being funded through the initial pivotal readouts for dom, quemli and cas, including PEAK-1; expected efficacy or safety of our investigational products, including the durability of patient responses to casdatifan; potential of our investigational products and portfolio, including our investigational products potential to be best or first in class; anticipated benefits of our collaborations with Gilead, Taiho and AstraZeneca; achievement and expected timing of clinical and developmental milestones, including the initiation of PEAK-1 and the timing of new data; initiation of new clinical trials and the design of current clinical trials, including planned cohorts and treatment regimen; the expectation that data from current studies such as ARC-20 are indicative of what will be shown in later studies such as PEAK-1; dosing for any of our investigation products and planned tablet formulation; the potential market and patient population for any of our investigational products; possible first to market advantage for any of our investigational products; adoption of any of our investigational products once improved, including any such product becoming a standard of care; and benefits of our collaboration, including the benefits we expect from our collaboration with AstraZeneca. These forward-looking statements are subject to a number of risks, uncertainties and assumptions that may cause actual results to differ materially from those contained in any forward-looking statements we may make, including, but not limited to: risks associated with preliminary or interim clinical data or preclinical data not being guarantees that future data will be similar; the unexpected emergence of adverse events or other undesirable side effects; difficulties or delays in initiating, conducting or completing our clinical trials due to difficulties or delays in the regulatory process, enrolling subjects or manufacturing or supplying product for such clinical trials, all of which may be exacerbated by unfavorable global economic, political and trade conditions; risks associated with our collaboration arrangement with Gilead including our dependence on Gilead for the successful development and commercialization of our investigational products; changes in the competitive landscape; our ability to successfully market and commercialize any investigational product that is approved; our limited operating history and our ability to manage our growth; our ability to obtain and maintain intellectual property protection for our product candidates; and the inherent uncertainty associated with pharmaceutical product development and clinical trials. It is not possible for our management to predict all risks, nor can we assess the impact of all factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially and adversely from those anticipated or implied in the forward-looking statements. Further information on these and other factors that could affect the forward-looking statements made herein are described in our most recent periodic reports filed with the U.S. Securities and Exchange Commission filed with the U.S. Securities and Exchange Commission. You should not rely upon forward-looking statements as predictions of future events. Except as required by law, neither we nor any other person assumes responsibility for the accuracy and completeness of the forward-looking statements. We undertake no obligation to update publicly any forward-looking statements for any reason after the date of this presentation to conform these statements to actual results or to changes in our expectations. Third-Party Sources Disclaimer: Additionally, this presentation contains certain information related to or based on studies, publications, surveys and other data obtained from third-party sources, and our own internal estimates and research, including without limitation relating to market size and potential. This information is based on a number of assumptions, projections and estimates, including with respect to our future performance and the future performance of markets in which we operate, and are necessarily subject to a high degree of uncertainty and risk and you are cautioned not to give undue weight to such estimates. No Regulatory Approval: All of Arcus’s molecules are investigational and Arcus (and Gilead for all of the molecules in each optioned program) has not received approval from any regulatory authority for any use globally, nor established the safety and efficacy of these investigational molecules. Notice of Trademarks: The Arcus name and logo are the property of Arcus. All other trademarks used herein are the property of their respective owners and are used for reference purposes only. Such use should not be construed as an endorsement of Arcus. 2 Forward-looking Statements/Safe Harbor Cas: casdatifan; dom: domvanalimab; quemli: quemliclustat
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© Arcus Biosciences 2025 TOPIC PRESENTER(S) Casdatifan Value Proposition Dr. Terry Rosen CEO, Arcus Biosciences ARC-20 Cas + Cabo Cohort Data Dr. Richard Markus CMO, Arcus Biosciences Casdatifan Development Plan Dr. Richard Markus CMO, Arcus Biosciences Opportunity for Casdatifan Jennifer Jarrett COO, Arcus Biosciences Closing Remarks Dr. Terry Rosen CEO, Arcus Biosciences Q&A All 3 Agenda Cabo: cabozantinib; cas: casdatifan
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© Arcus Biosciences 2025 4 Initial Data from the Cas + Cabo Cohort Were Presented in an Oral Presentation at ASCO 2025 ASCO: American Society of Clinical Oncology; Cabo: cabozantinib; cas: casdatifan #ASCO25 PRESENTED BY: Toni K Choueiri, MD, FASCO Presentation is property of the author and ASCO. Permission required for reuse; contact persmissions@asco.org 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 Ornstein, MD, MA2; Pedro Barata, MD, FACP3; Marc Matrana, MD, FACP4; Jamie Merchan, MD5; Craig Gedye, MBChB, FRACP, PhD6; Clara Hwang, MD7; Rohit Kumar, MD8; Jae Lyun Lee, MD, PhD9; Yinghui Guan, MS, PhD10; Mohammad Ghasemi, PhD10; Syed Quadri, MD10; Chris Negro, MS10; Jianfen Chen, MS10; Paul Foster, PhD10; Deepti Warad, MBBS10; Bradley A McGregor, MD1; Sun Young Rha, MD, PhD11; Alexandra Drakaki, MD, PhD12 1Dana-Farber Cancer Institute, Boston, MA, USA; 2Cleveland Clinic, Cleveland, OH, USA; 3University Hospitals Seidman Cancer Center, Cleveland, OH, USA; 4Oschsner Health, New Orleans, LA, USA; 5Department of Medical Oncology, University of Miami Leonard M. Miller School of Medicine, University of Miami, Miami, FL, USA; 6ICON Cancer Centre Adelaide, Kurralta Park, SA, Australia; 7Henry Ford Cancer-Detroit, Detroit, MI, USA; 8James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA; 9Asan Medical Center University of Ulsan College of Medicine, Seoul, South Korea; 10Arcus Biosciences, Inc., Hayward, CA, USA; 11Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea; 12Division of Hematology/Oncology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA
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© Arcus Biosciences 2025 5 Arcus is Capitalized to Advance its Broad Portfolio of Late- Stage Programs Through Phase 3 Readouts 1H25: first half of 2025; 1L: first-line; 2Q25: second quarter of 2025; ASCO: American Society of Clinical Oncology; cabo: cabozantinib; cas: casdatifan; dom: domvanalimab; I&I: immunology & inflammation; NSCLC: non- small cell lung cancer; Ph: phase; quemli: quemliclustat; R&D: research & development * cash, cash equivalents and marketable securities as of March 31, 2025 ** runway estimate based on cash, cash equivalents, marketable securities, and available facilities DOMVANALIMAB: THREE PHASE 3 STUDIES 1L Gastric Approaching Ph 3 Data 1L NSCLC (all comers) Ongoing Stage 3 NSCLC Ongoing CASDATIFAN: POTENTIAL BEST-IN-CLASS HIF-2α INHIBITOR Validated mechanism and compelling market opportunity cas + cabo oral at ASCO WORLD-CLASS DRUG DISCOVERY $1 BILLION IN CASH* Funded through initial pivotal readouts for dom, quemli and cas, which include PEAK-1** Small molecules focused on oncology and I&I Phase 3 initiation expected in 2Q25
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© Arcus Biosciences 2025 Casdatifan Value Proposition Dr. Terry Rosen CEO, Arcus Biosciences 6
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© Arcus Biosciences 2025 ROBUST EFFICACY RESPONSES ALREADY APPEAR DURABLE • The 46% ORR for cas + cabo exceeds benchmarks for either agent alone1 and the Phase 2 LITESPARK-003 benchmark for belz + cabo2 Initial Cas + Cabo Data Substantially De-Risk PEAK-1 Belz: belzutifan; cabo: cabozantinib; cas: casdatifan; DCO: data cutoff date; IO: immunotherapy; ORR: overall response rate; SD: stable disease; TEAE: treatment -emergent adverse event 1. For cabo monotherapy - Phase 3, CONTACT-03 , Pal et al 2023; Phase 3 METEOR, Choueiri et al 2015; cas monotherapy: Arcus ENA 2024 presentation 2. Choueiri et al. 2023, Lancet Oncology HIGH DOSE INTENSITY OF BOTH DRUGS • AE profile for cas + cabo is consistent with that expected for either agent alone • No cas-related TEAEs > grade 3 • 88-95% dose intensity achieved for both cas and cabo enabling optimization of efficacy for the combination • As of the DCO, only 5% of safety evaluable patients discontinued a drug due to an AE and no patients have discontinued both drugs • All responses to date have confirmed and all 11 responders remain on treatment as of today • Majority of patients with best response of SD also remain on treatment, indicating that even SD patients are experiencing meaningful benefit NO SIGNS OF OVERLAPPING TOXICITY 7
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© Arcus Biosciences 2025 8 Two Datasets Now Demonstrate Casdatifan's Potential to be the Best-in-Class HIF-2α Inhibitor for ccRCC Data above are not from head-to-head studies. Cross-trial data interpretation should be considered with caution as it is limited by differences in study population, sample size, inclusion and exclusion criteria and many other factors. 2L: second-line; belz: belzutifan; cabo: cabozantinib; cas: casdatifan; ccRCC: clear-cell renal cell carcinoma; cORR: confirmed overall response rate; IO: immunotherapy; m: month; PFS: progression-free survival; TBD: to be determined a. Data cutoff date: March 14, 2025 b. Data cutoff date: January 3, 2025 1. Choueiri et al. 2023, Lancet Oncology 2. Albiges L. et al. Abstract LBA88, ESMO 2023 100mg Cas + 60mg cabo in IO- experienced ccRCCa (n=24) 46% 5% 25-33% <20% TBD 9.7-12m+ LOW RATE OF PRIMARY PROGRESSION: Cas mono in 2L+ ccRCCb (n=89 across 3 cohorts) Despite limited follow-up, key efficacy measures exceed those for the Phase 2 LITESPARK-003 study (belzutifan + cabozantinib) All three cohorts demonstrated improvement on every efficacy endpoint evaluated relative to the Phase 3 LITESPARK-005 study belz + cabo (LS-003)1 24m follow-up 21% belz (LS-005)2 26m follow-up 34% 5.6mMEDIAN PFS: 31% cas + cabo (ARC-20) 5m follow-up 13.7m 6% HIGH cORR: cas (ARC-20) 5-15m follow-up
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© Arcus Biosciences 2025 Casdatifan has an Optimal Pharmacological Profile Relative to That of the Competitor Belzutifan GREATER INHIBITION OF HIF-2α / PD EFFECT • 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 • Casdatifan achieves this same effect on EPO at only 20mg, one-fifth the "going forward" dose of 100mg • Casdatifan's effect on EPO is highly durable over multiple months, while belzutifan appears to lose its PD effect within 3 months • Belzutifan does not achieve meaningfully higher drug exposure at doses above 120mg and, therefore, cannot achieve a more robust PD effect • Casdatifan has linear, dose-proportional pharmacokinetics LINEAR, DOSE PROPORTIONAL PK OPTIMAL HALF-LIFE AND FORMULATION • Belzutifan's half-life is only ~14h, versus ~24h for casdatifan • Belzutifan is dosed as three pills once-daily (40mg x 3) vs a planned 100mg tablet once-daily for casdatifan 9 EPO: erythropoietin; h: hours; PD: pharmacodynamic; PK: pharmacokinetic
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© Arcus Biosciences 2025 Primary progressive disease <20% 34% cORR (“post anti-PD-1/TKI”) 25-33% 21% mPFS (“post anti-PD-1/TKI”) 9.7-12m+ 5.6m Grade 3 Hypoxia High single digits Low teens TKI combo partner in post-IO setting + cabo + lenva (data in 2027) + zanza (data in ??) 1L strategy + anti-PD-1/CTLA-4 (volru; TKI-free) + pembro (anti-PD-1) + lenva (TKI) Pill burden 1 (+1 for cabo) 3 (+2 for lenva) The HIF-2α Market is a 2-Horse Race and Cas is Poised to Become the HIF-2α Treatment of Choice in ccRCC 1L: first-line; belz: belzutifan; cabo: cabozantinib; cas: casdatifan; ccRCC: clear-cell renal cell carcinoma; cORR: confirmed overall response rate; IO: immunotherapy; lenva: lenvatinib; mPFS: median progression free survival; m: months; pembro: pembrolizumab; volru: volrustomig; zanza: zanzalintinib 1. Clinical data from LITESPARK-005. Sources: Albiges L. et al. Abstract LBA88, ESMO 2023; Choueiri et al. 2024. belzutifan1 EFFICACY & SAFETY DATA BASED ON ARC-20 (CAS) AND LITESPARK-005 (BELZ), EACH FROM MONOTHERAPY COHORTS IN “LATE-LINE” PATIENTS casdatifan 10
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© Arcus Biosciences 2025 eVOLVE-RCC02 is Targeting the 1L Setting with the First HIF-2α-Containing TKI-Free Regimen 1L: first-line; AZ: AstraZeneca; cas: casdatifan; ccRCC: clear cell renal cell carcinoma; volru: volrustomig • Utilizing a seamless Phase 1b/3 design • Potential first-in-class, TKI-sparing combination • Volru has demonstrated exciting preliminary data in 1L ccRCC • Clinical collaboration between Arcus and AZ where both parties retain all economics / rights to their respective molecules • Evaluating casdatifan in combination with AZ’s volrustomig (anti-CTLA-4/anti-PD-1 bispecific) • AZ to sponsor the study and study costs to be shared • Enables Arcus to target the 1L setting in a cost- and resource-efficient manner cas + volrustomig (anti-CTLA-4/anti-PD-1 bispecific) 11
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© Arcus Biosciences 2025 CURRENT SOC 1L Favorable Risk Watch and Wait anti-PD-1 + TKI TKI mono 1L all-comers anti-PD-1 + anti-CTLA-4 anti-PD-1 + TKI 2L (Post-IO) TKI mono 3L+ (Post-IO & TKI) mTOR HIF-2α (belz) POTENTIAL PARADIGM SHIFT HIF-2α mono cas HIF-2α + anti-PD-1/CTLA-4 cas +volrustomig HIF-2α + anti-PD-1 cas + zim HIF-2α + TKI cas + cabo HIF-2α mono cas TKI mono mTOR HIF-2α (belz) Casdatifan Has the Potential to Change the Treatment Paradigm in ccRCC and Displace TKIs in Early Lines 1L: first-line; 2L: second-line; 3L: third-line; belz: belzutifan; cabo: cabozantinib; cas: casdatifan; ccRCC: clear cell renal cell carcinoma; IO: immunotherapy; mono: monotherapy; zim: zimberelimab12
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© Arcus Biosciences 2025 ARC-20 Cas + Cabo Cohort Dr. Richard Markus CMO, Arcus Biosciences 13
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© Arcus Biosciences 2025 Data Presented at ASCO Were From the Cas + Cabo Cohort of the ARC-20 Expansion Cohorts 1L: first-line; 2L: second-line; ASCO GU: American Society of Clinical Oncology Genitourinary Cancers; BID: twice daily; cabo: cabozantinib; cas: casdatifan; ccRCC: clear cell renal cell carcinoma; IO: immunotherapy; mono: monotherapy; ORR: overall response rate; PFS: progression- free survival; Q3W: every three weeks; QD: once daily 2L+ ccRCC Casdatifan mono 50mg BID capsule 2L+ ccRCC Casdatifan mono 50mg QD capsule 2L+ ccRCC Casdatifan mono 150mg QD 2L+ ccRCC Casdatifan mono 100mg QD tablet Favorable -risk 1L ccRCC Casdatifan mono 100mg QD 1L ccRCC Casdatifan 100mg QD + Zimberelimab 360mg Q3W Post-IO ccRCC Casdatifan mono 100mg QD Post-IO ccRCC Casdatifan 100mg QD + Cabozantinib 60mg QD Casdatifan monotherapy DOSE EXPANSION N = ~30 per cohort, except cas + cabo (n=45) DOSE ESCALATION Patients with advanced solid tumors 150mg QD 50mg BID 50mg QD 20mg QD 200mg QD 14 Data presented at ASCO, June 1, 2025 Data presented at ASCO GU, February 2025 At the March 14 data cutoff: • 42 patients were evaluable for safety (had received at least one dose of cas and had at least one month follow-up) • 24 patients were evaluable for efficacy (had reached at least 12 weeks follow-up) • To date, over 200 patients have received casdatifan across all cohorts of ARC-20
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© Arcus Biosciences 2025 Patient Characteristics in the Casdatifan Plus Cabozantinib Expansion Cohort ECOG PS: Eastern Cooperative Oncology Group Performance Status; IMDC: International Metastatic Renal Cell Carcinoma Database Consortium; IO: immunotherapy; Presented at ASCO 2025 by Toni K Choueiri, MD, FASCO. Data cutoff: March 14, 2025. aSafety population included patients who received any amount of study drug and had at least 1 month of safety follow -up at the data cutoff date. 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%) Poor 4 (10%) Number of prior regimens, n (%) 1 35 (83%) 2+ 7 (17%) Prior treatment, n (%) VEGFR-TKI plus IO 17 (40%) IO only 25 (60%) Patients were enrolled at 15 sites across 3 countries 15
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© Arcus Biosciences 2025 16 Confirmed ORR of 46% in Patients Eligible for a Minimum of 12 Weeks Follow-Up AE: adverse event; CR: complete response; ORR: overall response rate; PD: progressive disease; PR: partial response; SD: stable disease Presented at ASCO 2025 by Toni K Choueiri, MD, FASCO. Data cutoff date: March 14, 2025. aAll eligible patients who received any study treatment and achieved a minimum of 12 weeks follow -up or discontinued due to progression or death. bInclusive of one patient who had confirmed PR after March 14, 2025. 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 Overall Response, n (%) CR 1 (4%) PRb 10 (42%) SD 12 (50%) PD 1 (4%) • To date, all responses have confirmed and all responders remain on treatment
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© Arcus Biosciences 202517 Almost All Patients Achieved Tumor Reductiona,b -80 -60 -40 -20 0 20 40 60 80 100 SLD: sum of lesion diameter; ORR: overall response rate Presented at ASCO 2025 by Toni K Choueiri, MD, FASCO. Data cutoff date: March 14, 2025. aAll eligible patients who received any study treatment and achieved a minimum of 12 weeks follow -up or discontinued due to progression or death. bInclusive of one patient who had confirmed PR after March 14, 2025. n = 24 Best Percent Change From Baseline in SLD, % Complete Response OngoingPartial Response Stable Disease Progressive Disease
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© Arcus Biosciences 202518 Tumor Reduction Has Deepened Over Time and Responses Already Appear Very Durable ORR: overall response rate; SLD: sum of lesion diameter Data cutoff date: March 14, 2025. All eligible patients who received any study treatment and achieved a minimum of 12 weeks follow -up or discontinued due to progression or death. 0 5 10 15 20 25 30 35 40 45 -80 -60 -40 -20 0 20 40 Percent Change From Baseline in SLD (%) Time (Weeks) Complete Response Treatment OngoingPartial Response Stable Disease Progressive Disease
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© Arcus Biosciences 2025 19 Most Patients Remain on Treatmenta,b Presented at ASCO 2025 by Toni K Choueiri, MD, FASCO. Data cutoff date: March 14, 2025. aAll eligible patients who received any study treatment and achieved a minimum of 12 weeks follow -up or discontinued due to progression or death. bInclusive of one patient who had confirmed PR after March 14, 2025. Time on Treatment, Weeks 0 5 10 15 20 25 30 35 40 45 n = 24 Complete Response OngoingPartial Response Stable Disease Progressive Disease
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© Arcus Biosciences 202520 CAS 100MG QD + CABO 60MG QD* N=27 CAS 100MG QD* N=29 CAS 50MG QD* N=31 CAS 50MG BID* N=33 Median duration of follow- up, months 3.7 5.1 12.3 15.5 Median Tx duration, months 3.0 4.1 10.6 7.1 Cas relative dose intensity, median 94.9% 98.6% 100.0% 98.6% Cabo relative dose intensity, median 88.0% NA NA NA Casdatifan Dose Intensity was Consistently 95%+, Driving Efficacy and Durability BID: twice daily; cabo: cabozantinib; cas: casdatifan; NA: not applicable; QD: once daily; tx: therapy *Data cutoff date: January 3, 2025
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© Arcus Biosciences 2025 21 TRAEs (Any Grade): Safety Profile was Consistent with Expectations for Cas and Cabo Cabo: cabozantinib, cas: casdatifan; TRAE: treatment related adverse event Presented at ASCO 2025 by Toni K Choueiri, MD, FASCO. Data cutoff: March 14, 2025. aSafety population included patients who received any amount of study drug and had at least 1 month of safety follow -up at the data cutoff date. bTreatment-emergent adverse events (any grade) related to casdatifan, cabozantinib, or any study drug reported in ≥ 15% of patients in any treatment arm. • Most cases of anemia and fatigue did not require a dose change and resolved 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%) Anemia 29 (69%) 18 (43%) 29 (69%) Fatigue 20 (48%) 23 (55%) 23 (55%) Alanine aminotransferase increased 8 (19%) 16 (38%) 16 (38%) Diarrhea 6 (14%) 15 (36%) 15 (36%) Aspartate aminotransferase increased 6 (14%) 14 (33%) 14 (33%) Platelet count decreased 5 (12%) 12 (29%) 12 (29%) Nausea 5 (12%) 10 (24%) 10 (24%) Dizziness 7 (17%) 6 (14%) 8 (19%)
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© Arcus Biosciences 2025 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%) Hypoxia 3 (7%) 0 3 (7%) Hypertension 0 2 (5%) 2 (5%) Neutrophil count decreased 1 (2%) 2 (5%) 2 (5%) Very Few Grade 3 or Higher Treatment Related AEs AE: adverse event Presented at ASCO 2025 by Toni K Choueiri, MD, FASCO. Data cutoff: March 14, 2025. aSafety population included patients who received any amount of study drug and had at least 1 month of safety follow-up at the data cutoff date. bTreatment-emergent adverse events (grade 3 or higher) related to casdatifan, cabozantinib, or any study drug reported in ≥ 3% of patients in any treatment arm. • No casdatifan-related grade 4 or 5 AEs were observed 22
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© Arcus Biosciences 2025 23 AEs Were Manageable with Dose Reductions, Leading to Very Few Discontinuations TEAE: treatment-emergent adverse event Presented at ASCO 2025 by Toni K Choueiri, MD, FASCO. Data cutoff: March 14, 2025. aSafety population included patients who received any amount of study drug and had at least 1 month of safety follow-up at the data cutoff date. bTreatment-emergent adverse events (any grade) leading to dose reduction in casdatifan, cabozantinib, or any study drug reported in ≥ 3% of patients in any treatment arm. • Only 2 patients (of 42 safety evaluable) discontinued a treatment due to a TEAE (hypoxia and drug hypersensitivity), and no patients discontinued both treatments due to a TEAE 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 (2%) 4 (10%) Hypoxia 4 (10%) 0 4(10%) Palmar-plantar erythrodysesthesia 0 2 (5%) 2 (5%) Stomatitis 0 2 (5%) 2 (5%)
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© Arcus Biosciences 2025 24 Key Takeaways from the Cas + Cabo Cohort Cabo: cabozantinib; cas: casdatifan; ORR: overall response rate 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 appears very manageable, and consistent with the individual agents • Dose intensity of cas in the combination is very high and similar to monotherapy Very low rate of discontinuations and "short" dose interruptions ensure that drug is "on board" almost continuously
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© Arcus Biosciences 2025 25 8 Cohorts of ARC-20 Study Enable A Steady Cadence of Data Over the Next ~18 Months 1L: first-line; ASCO: American Society of Clinical Oncology; BID: twice daily; cabo: cabozantinib; cas: casdatifan; IO: immunotherapy; mono: monotherapy; ORR: overall response rate; PFS: progression- free survival; QD: once daily; zim: zimberelimab TIMING ARC-20 COHORTS EVENT Early 2025 • 50mg BID • 50mg QD • 100mg QD Updated data from 50mg BID, 50mg QD (ORR, PFS) Initial data from 100mg QD tablet (ORR) mono cohort June 2025 • cas + cabo (post-IO) Safety and initial efficacy data for the cas + cabo cohort oral presentation at ASCO Fall 2025 • 50mg BID • 50mg QD • 100mg QD • 150mg QD • More mature safety and efficacy data for monotherapy cohorts (ORR, PFS) 2026 • cas + cabo • cas mono (1L favorable risk) • cas +zim (1L) • cas mono (post-IO) • More mature data on cas + cabo combination • Data from new ARC-20 cohorts in earlier line settings
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© Arcus Biosciences 2025 26 PFS Kaplan-Meier Curves Shown at ASCO GU Bode Well for Updated PFS for Cas Mono Cohorts Later this Year ASCO GU: American Society of Clinical Oncology Genitourinary Cancers Symposium; BID: twice daily; CI: confidence interval; DC O: data cutoff; mPFS: median progression-free survival; NE: not estimable; QD: once daily 1. IA1 for LITESPARK-005. Source: Albiges L. et al. Abstract LBA88, ESMO 2023; PFS was measured according to RECIST v1.0 and estimated using Kaplan- Meier methodology. Data cutoff date: January 3, 2025 Median follow-up of 15 months Censored 1.0 Kaplan-Meier Estimates of Progression Free Survival Patients at risk: 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 28 28 22 21 21 19 19 18 18 16 13 8 5 2 0 Kaplan-Meier Estimates of Progression Free Survival Median PFS, months (95% CI) Median follow-up (range) 9.7 (5.5, NE) 15 (7–19+) months Patients at risk: 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 32 32 26 24 23 23 18 15 15 14 11 11 11 9 8 2 2 0 Median follow-up of 12 months 50mg BID Cohort (n=32) 50mg QD Cohort (n=28) • mPFS for belzutifan in Phase 3 LITESPARK-003 was 5.6 months with 18 months median follow-up Median PFS, months (95% CI) Median follow-up (range) NE (6.8, NE) 12 (9–14+) months
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© Arcus Biosciences 2025 Casdatifan Development Plan Dr. Richard Markus CMO, Arcus Biosciences 27
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© Arcus Biosciences 2025 First Phase 3 Study for Cas Has a Simple Design that Utilizes the Preferred SOC in Post-IO ccRCC 28 1L: first-line; cabo: cabozantinib: cas: casdatifan; ccRCC: clear cell renal cell carcinoma; DCR: disease control rate; DOR: duration of response; IO: immunotherapy; ORR: objective response rate; OS: overall survival; PFS: progression free survival; R: randomized; RCC: renal cell carcinoma; RECIST: Response Evaluation Criteria in Solid Tumors; SOC: standard of care PRIMARY ENDPOINT: • PFS KEY SECONDARY ENDPOINTS: • OS • ORR, DOR, DCR PATIENT POPULATION: • Unresectable, locally advanced or metastatic ccRCC • Measurable disease per RECIST 1.1 • Have had prior anti- PD-1/PD-L1 (either in adjuvant or 1L metastatic setting) • Have not received cabozantinib • HIF-2α-inhibitor naïve 100MG CASDATIFAN + CABOZANTINIB PLACEBO + CABOZANTINIB R 2:1 N~700 PEAK-1 is Expected to Initiate Imminently
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© Arcus Biosciences 2025 New Cohorts Added to ARC-20 to Evaluate New Opportunities to Displace TKIs 1L: first-line; 2L: second-line; ASCO: American Society of Clinical Oncology Genitourinary Cancers; BID: twice daily; cas: casdatifan; ccRCC: clear cell renal cell carcinoma; IO: immunotherapy; mono: monotherapy; Q3W: every three weeks; QD: once daily 2L+ ccRCC casdatifan mono 50mg BID capsule 2L+ ccRCC casdatifan mono 50mg QD capsule 2L+ ccRCC casdatifan mono 150mg QD 2L+ ccRCC casdatifan mono 100mg QD tablet Favorable -risk 1L ccRCC casdatifan mono 100mg QD 1L ccRCC casdatifan 100mg QD + zimberelimab 360mg Q3W Post-IO ccRCC casdatifan mono 100mg QD Post-IO ccRCC casdatifan 100mg QD + cabozantinib 60mg QD Data presented at ASCO GU 2025 Satisfies Project Optimus and confirmed 100mg QD tablet as the "going forward" dose and formulation Data presented at ASCO 2025 Generated data to support the Phase 3 PEAK-1 study New cohorts added and currently enrolling; Designed to inform the potential of cas in early- line settings EXPANSION COHORTS 29
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© Arcus Biosciences 2025 Opportunity for Casdatifan Jennifer Jarrett COO, Arcus Biosciences 30
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© Arcus Biosciences 2025 - 200 400 600 800 1,000 1,200 1,400 1,600 1,800 2,000 31 Belzutifan Sales Have Grown Exponentially Despite its Usage Being Limited to Late-line ccRCC 3L: third-line; Apr: April; cas: casdatifan; ccRCC: clear cell renal cell carcinoma; Dec: December; LTM: last twelve months; Rx: prescriptions; SOC: standard of care Source: IQVIA, Merck Q1 2025 Earnings 154% growth from Dec ’23 (approval in ccRCC) to Apr ’25 • Belzutifan has rapidly established itself as the SOC in the 3L+ ccRCC setting − High rate of primary progression likely limits use in earlier line settings • LTM Sales of >$560M in the U.S.; Run rate sales based on April Rx's are now $720M+ • Cas has the potential to meaningfully exceed this based on an improved efficacy profile and superior combination strategy in earlier lines Monthly Belzutifan Prescriptions
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© Arcus Biosciences 2025 17% 4% 16% 9% 21% 13% 32% 8% 5% 29% 4% 12% 4% 6% 3% 3% 10% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 1L RCC 2L RCC % Patient Share chemo belz (+/- other) non-cabo TKI mono avelumab + atixinib lenva + everolimus nivo mono cabo mono nivo + ipi nivo + cabo pembro + lenva pembro + axitinib Potential to replace with cas + volru Potential to replace with cas + cabo 32 Initial Cas Development Plan Targets the Largest Market Segments and Could Expand Share Within These Segments 1L: first-line; 2L: second-line; belz: belzutifan; cabo: cabozantinib; cas: casdatifan; ccRCC: clear cell renal cell carcinoma; chemo: chemotherapy; ipi: ipilimumab; lenva: lenvatinib; mono: monotherapy; nivo: nivolumab; pembro: pembrolizumab; volru: volrustomig Sources - Epi: DRG, GlobalData | Share: Arcus primary research, US May 2024 (n=49) 2024 ccRCC | US Market Share ipi-nivo cabo mono ~75% 1L eligible for cabo in 2L 12.6K PATIENTS 8.8K PATIENTS
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© Arcus Biosciences 2025 33 Cas + Cabo Has the Potential to Establish a New SOC in IO- Experienced ccRCC • Cabo is the preferred TKI in IO-experienced ccRCC due to a perceived better safety profile and simpler titration • Cas is the only HIF-2α inhibitor being developed in Phase 3 with cabo • Cas + cabo has the potential to displace TKI monotherapy by prolonging PFS without significant additional toxicity • 2-drug regimen enables continued treatment on at least one therapy and optimal management of TKI-related toxicities • With LITESPARK-011 readout delayed, the gap between this study and PEAK-1 has significantly narrowed Establishing Cas + Cabo as the HIF-2α + TKI Combination of Choice Cabo: cabozantinib; cas: casdatifan; ccRCC: clear cell renal cell carcinoma; IO: immunotherapy; PFS: progression-free survival; SOC: standard of care Cas 100mg (1 x 100mg) Cabo 20-60mg (1 x Xmg)
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© Arcus Biosciences 2025 34 Avoiding Overlapping Toxicity is Key to Maintaining Patients on Therapy and Positions HIF-2α as the Ideal Backbone PPE: palmar-plantar erythrodysesthesia • Anemia • Hypoxia • Fatigue • Diarrhea • Rash • Hepatotoxicity • Hypothyroidism • Pneumonitis • Diarrhea • Rash • Hepatotoxicity • Hypothyroidism • Hypertension • Fatigue • PPE • Diarrhea • Rash • Hepatotoxicity • Hypothyroidism • Fatigue • Pneumonitis • Pyrexia TKIs anti-PD-1 anti-PD-1/CTLA-4 Casdatifan 100mg coated tablet 25mg coated tablet
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© Arcus Biosciences 2025 CURRENT SOC POTENTIAL FUTURE TREATMENT MARKET SIZE (MAJOR MARKETS1,2) IO-naive metastatic Anti-PD-1 + CTLA4 cas + volru 21k patients Post-IO metastatic TKI mono cas + cabo 19k patients Post-IO & post-TKI mTOR, TKI, HIF-2α 12k patients 35 Our Initial Focus Is on the IO-naive and Post-IO Settings, Both Multi-Billion Dollar Market Opportunities New cohorts added to ARC-20: • 1L (cas + zim) • 1L favorable risk (cas mono) • 1L/2L Post-IO/ TKI-naive (cas mono) New tumor types CAS FUTURE DEVELOPMENT ~$3B OPPORTUNITY ~$2B OPPORTUNITY 1L: first-line; 2L: second-line; B: billion; cabo: cabozantinib; cas: casdatifan; ccRCC: clear cell renal cell carcinoma; IO: immunotherapy; mono: monotherapy; mTOR: mechanistic target of rapamycin; SOC: standard of care; volru: volrustomig; zim: zimberelimab 1. Drug Treatable Addressable Populations (Major Markets, 2024); Decision Resources Group, Arcus analysis 2. Major Markets (US, EU5, JP) - total projected 2034
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© Arcus Biosciences 2025 TODAY 2027+ 2030+ 1L ~16mo DoT 2L ~11mo DoT 3L ~8mo DoT 3K TOTAL 9K TOTAL 16K TOTAL As Casdatifan Moves Up in the Treatment Paradigm, the U.S. Market Opportunity Will Grow Substantially 1L: first-line; 2L: second-line; 3L: third-line; ccRCC: clear cell renal cell carcinoma; DoT: duration of therapy; mo: months Source: Primary market research. DRG epi projections. ~1K ~2K ~6K ~3K ~6K ~1K ~9K Potential ccRCC Patients on HIF-2α Inhibitors over Time (US, Annual) 36
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© Arcus Biosciences 2025 Closing Remarks Dr. Terry Rosen CEO, Arcus Biosciences 37
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© Arcus Biosciences 2025 TIMING SETTING EVENT Fall 2025 2L+ (Post-IO & TKI) ccRCC • More mature data for cas mono from ARC-20 Throughout 2026 1L/2L ccRCC • More mature cas + cabo data from ARC-20 • Data from three new cas cohorts added to ARC- 20 (cas + zim in 1L, cas mono in 1L favorable risk, and cas mono in 1L/2L TKI-naive) 38 Rapid Advancement and Expansion of the Cas Program Is Our Priority over the Next Year 1L: first-line; 2L: second-line; belz: belzutifan; cas: casdatifan; ccRCC: clear cell renal cell carcinoma; IO: immunotherapy; mono: monotherapy; mPFS: median progression-free survival; ORR: overall response rate; PD: progressive disease; SOC: standard of care; zim: zimberelimab *https://www.precedenceresearch.com/kidney-cancer-drugs-market Cas is Poised to Be the HIF-2α Inhibitor of Choice for RCC • HIF-2α inhibitors is expected to become another SOC in the $6B+ ccRCC market*, in addition to anti-PD-1's and TKIs • HIF-2α market is currently a "2-horse" race between cas and belz • Cas has a potential best-in-class profile, both as monotherapy and in combination with other agents • We are pursuing a broad and differentiated development strategy to drive cas usage to earlier lines of therapy Multiple Data Events Coming Over the Next ~18 Months
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© Arcus Biosciences 2025 PEAK INVESMENT YEAR PHASE 3 TRIAL NAME STATUS INDICATION PATIENTS (MAJOR MARKETS1,2) MARKET POTENTIAL (MAJOR MARKETS2) CAS HIF-2α small molecule inhibitor 2027+ To Begin Shortly Post-IO ccRCC 19K ~$2B To Begin Shortly IO-naive ccRCC 21K ~$3B DOM (+ ZIM) Fc-silent anti-TIGIT mAb + anti-PD-1 mAb 2025 Data Expected 2026 (event-driven) 1L Gastric/GEJ/EA C – all comers 105K ~$3B Ongoing 1L NSCLC – all comers 307K ~$10B Ongoing Stage 3 NSCLC, PD- L1>1% 35K 3 ~$2B QUEMLI CD73 small molecule inhibitor 2025 Ongoing 1L PDAC 109K >$4B Designed to improve upon the current standard of care 39 Three Phase 3 Programs Targeting Substantial Market Opportunities and Unmet Medical Need 1L: first-line; 2L: second-line; 3L: third-line; casdatifan; ccRCC: clear cell renal cell carcinoma; dom: domvanalimab; EAC: esophageal adenocarcinoma; GEJ: gastroesophageal junction; IO: immunotherapy; mAb: monoclonal antibody; NSCLC: non-small cell lung cancer; PDAC: pancreatic ductal adenocarcinoma; quemli: quemliclustat; zim: zimberelimab 1. Drug Treatable Addressable Populations (Major Markets, 2024); Decision Resources Group, Arcus analysis 2. Major Markets (US, EU5, JP) - total projected 2034 PD-(L)1 + TIGIT opportunity, Q opportunity & Hif2α opportunity 3. cCRT responding patients