LITESPARK-011 Trial

[Slide 1] Summary and Conclusions Belzutifan + lenvatinib demonstrated superior PFS and ORR VS cabozantinib in participants with OS favored belzutifan + lenvatinib but did not reach statistical significance and will be tested advanced clear cell RCC following anti-PD-(L)1 therapy further The safety at final profile analysis of belzutifan + lenvatinib was generally consistent with the profiles of the individual to worsening drugs in disease-specific symptoms and quality of life were similar between belzutifan + is the first phase 3 study of a HIF-2a inhibitor to show improved plus a VEGFR-TKI, outcomes and VS a the Time lenvatinib VS cabozantinib LITESPARK-011 phase 3 study in RCC in the post-PD-(L)1 setting new contemporary first VEGFR-TKI addresses unmet clinical need and anti-PD-(L)1 represents a therapy potential treatment Belzutifan option + lenvatinib for patients with RCC an that progressed after --- [Slide 2] Primary Endpoint: PFS per RECIST 1.1 by BICR 100 12 months 24 months Belzutifan + Cabozantinib Lenvatinib 90 (N = 376) (N = 371) 80 Events, n (%) 232 (62.5) 273 (72.6) Progression-free survival, % 70 Median, mo 14.8 10.7 55.0% (95% CI) (11.2-16.6) (9.2-11.1) 60 50 HR 0.70, 95% CI 0.59-0.84, 35.6% 40 1-sided P =.00007* 30 41.0% 20 10 19.1% 0 0 5 10 15 20 25 30 35 40 45 50 No. at Risk Months Belzutifan + 371 292 204 151 117 61 39 19 8 1 0 Lenvatinib Cabozantinib 376 279 166 102 78 33 10 2 0 0 0 denotes statistical significance (1-sided boundary 0.0047). Data cutoff date, IA2: 9 April 20

[Slide 1] TKI/HIF-Based Therapy in Refractory mRCC The Ur migos Broadcasting the - developments in - bancer Cabozantinib Belzutifan Lenva + Everolimus Lenva + Belzu CONTACT-03 LITESPARK-005 LenCabo LITESPARK-011 (n=254) (n=374) (n=90) (n=747) Median f/u 15.2 months 25.7 months 20.0 months 29.0 months ORR 41% 22% 53% 53% CR 1% 4% 0% 5% Primary PD 5% 34% 8% 6% mPFS 10.8 months 5.6 months 15.7 months 14.8 months PFS @ 18 mos 30% (est.) 24% 40% (est.) 36% at 24 months 100 100 100 100 90 90 90 90 80 80 80 83 80 84 Any gr anemia Any gr hypoxia 70 70 70 70 68 69 60 60 60 62 60 Gr3+ TEAE 62 50 50 50 50 40 40 40 40 30 30 30 30 20 20 20 20 18 10 15 10 10 NR NR 10 15 O 0 0 O o

[Slide 1 — "Combination Therapy in Refractory mRCC" cross-trial comparison (The Uromigos)] Cabozantinib Belzutifan Len+Everolimus Lenva+Belzu Cabo+Casdatifan CONTACT-03 LITESPARK-005 (LenCabo) KEYMAKER-03B ARC-20 (n=254) (n=374) (n=90) (n=64) (n=24) Median f/u: 15.2 mo 25.7 mo 20.0 mo 17.6 mo (NR) ORR: 41% 22% 53% 47% 46% CR: 1% 4% 0% 2% 4% Primary PD: 5% 34% 8% 0% 4% mPFS: 10.8 mo 5.6 mo 15.7 mo 12.5 mo NR PFS @ 18 mo: 30% (est.) 24% 40% (est.) 52% at 12 mo NR [Comparator/context slide — these are OTHER refractory-mRCC regimens (belzutifan MONOTHERAPY is LITESPARK-005, n=374), NOT the LITESPARK-011 belzutifan + lenvatinib primary result. Cross-trial; not head-to-head. Grade 3+ TEAE / any-grade anemia / any-grade hypoxia bar chart on the slide is figure-only and not transcribed.]

[Slide 1] Secondary Endpoint: DOR per RECIST 1.1 by BICR Belzutifan + 100 12 months 24 months Cabozantinib Lenvatinib 90 (N = 371) (N = 376) Pts with 80 195 151 response, n 66.7% 70 Median DOR, 23.0 (2.0 to 44.3+) 12.3 (1.8+ to 35.9+) Duration of response, % mo (range) 60 49.5% 50 40 50.0% 30 20 25.5% 10 0 0 5 10 15 20 25 30 35 40 45 50 No. at Risk Months Belzutifan + 195 179 135 101 66 42 29 8 4 0 0 Lenvatinib Cabozantinib 151 136 79 58 34 15 5 1 0 0 0 DOR, duration of response. Data cutoff date, IA2: 9 April 2025 --- [Slide 2] Summary of Treatment Exposure and Safetya Belzutifan + Belzutifan + Cabozantinib Cabozantinib Treatment-emergent AEs Lenvatinib Treatment-related AEs Lenvatinib (N = 371) (N = 371) (N = 370) (N = 370) Median duration of therapy, 16.8 13.2 Pts with AE, n (%) mo (range) (0.03-46.9) (0.4-41.9) Any 361 (97.6) 363 (97.8) Pts with AE, n (%) Grade 23 265 (71.6) 244 (65.8) Any 369 (99.7) 369 (99.5) Serious 98 (26.5) 63 (17.0) Grade >3 311 (84.1) 307 (82.7) Led to death 2 (0.5) 1 (0.3) Serious 191 (51.6) 163 (43.9) Led to dose reduction of: VEGFR-TKI 246 (66.5) 288 (77.6) Belzutifan 125 (33.8) NA Led to discontinuation of: All study drugs 41 (11.1) 42 (11.3) Belzutifan 62 (16.8) NA VEGFR-TKI 78 (21.1) 42 (11.3) Reported for the as-treated population, defined as all randomized pts who received at dose of study treatment Treatment-related AEs that led to death were thrombotic microangiopathy (n=1) and pneumonitis (n=1) in the belzutifan lenvatinib arm, and hemoplysis (n=1) in the cabozantinib arm. Data cutoff date, IA2: 9 April 2025 --- [Slide 3] Common Treatment-Emergent AEsᵃ Incidence >20% in Any Arm Belzutifan + Lenvatinib (N = 370) Cabozantinib (N = 371) Diarrhea 52.7% 70.1% Hypertension 58.9% 56.6% Anemia 69.2% 25.6% Fatigue 45.1% 40.7% Decreased appetite 39.2% 40.4% Nausea 40.5% 38.5% PPES 20.5% 51.2% Hypothyroidism 35.7% 28.0% Weight decreased 28.1% 29.4% Proteinuria 36.8% 19.4% AST increased 21.1% 33.7% ALT increased 18.9% 31.0% AEs of clinical interest and incidence <20% with Constipation 26.2% 22.6% belzutifan . lenvatinib vs cabozantinib included: Asthenia 28.4% 20.2% Hypoxia all grade: 15.4% vs 0% Vomiting 31.4% 16.2% Grade 23: 11.9% vs 0% Arthraigia 28.9% 16.7% Cardiac dysfunction all grade: 7.0% vs 1.1% Stomatitis 14.1% 28.0% Grade 23: 4.6% vs 0.5% Dysgeusia 12.4% 27.8% Headache 22.2% 12.4% 100 80 60 40 20 0 20 40 60 80 100 Incidence, % Any grade AEs Grade >3 AEs Any grade AEs Grade >3 AEs ALT. alanine aminotransferase; AST, aspartate aminotransferase; PPES, palmar-plantar erythrodysesthesia syndrome. "Collected up to 30 days after cessation of study treatment. Data cutoff date, IA2: 9 April 2025 --- [Slide 4] Summary and Conclusions Belzutifan + lenvatinib demonstrated superior PFS and ORR vs cabozantinib in participants with advanced clear cell RCC following anti-PD-(L)1 therapy OS favored belzutifan + lenvatinib but did not reach statistical significance and will be tested further at final analysis The safety profile of belzutifan + lenvatinib was generally consistent with the profiles of the individual drugs Time to worsening in disease-specific symptoms and quality of life were similar between belzutifan + lenvatinib vs cabozantinib LITESPARK-011 is the first phase 3 study of a HIF-2a inhibitor plus a VEGFR-TKI, and the first phase 3 study in RCC in the post-PD-(L)1 setting to show improved outcomes vs a contemporary VEGFR-TKI Belzutifan + lenvatinib addresses an unmet clinical need and represents a potential new treatment option for patients with RCC that progressed after anti-PD-(L)1 therapy

[Slide 1] ASCO "This is a positive trial, and I think it will be meaningful for patients. The combination met its PFS primary endpoint. The high ORR from the TKI helps de-risk the regimen, while belzutifan may drive more durable responses-with the understanding that patient selection and toxicity monitoring remain critical." Dr. Katy Beckermann Tennessee Oncology