KEYNOTE-B15 / EV-304 Trial

[Slide 1] KN905/EV303 B15/EV304 (n=808) NIAGARA (N=1063) EVPx3 -> cystectomy EVPx4 cystectomy Gem/Cis/Durva x4-> EVPx6 (P to 1yr) EVPx5 (P to 1yr) cystectomy (D to 1yr) The Ur migos™ R R R Gem/cisx4 Gem/cisx4 cystectomy cystectomy cystectomy Median follow up 26 months 33months 42 months %T2/%ctDNA+ve 17%/NA 20%/NA 40%/56% % cystectomy 87% 87% 88% % started/completed 66%/25% (6% ongoing) 56%/51% 71%/54% adjuvant therapy pCR rates 56% vs 33% 57% vs 9% 37% vs 27% 2 yr EFS 75% vs 39% 79% vs 66% 68% vs 60% EFS HR 0.40 (0.38-0.57) 0.53 (0.41-0.70) 0.68 (0.56-0.82) 2 yr os (study/control) 80% vs 63% 87% vs 81% 82% vs 75% os HR 0.50 (0.33-0.74) 0.65 (0.48-0.89) 0.75 (0.59-0.93) G3/4 AEs TRAE=45% TEAEs=63% vs 48% TRAEs=41% vs 41%

[Slide 1] KEYNOTE-B15/EV-304 Study (NCT04700124) Key Eligibility Criteria Enfortumab vedotin 1.25 mg/kg Enfortumab vedotin 1.25 mg/kg Adults with MIBC N = 405 d1 and d8 IV Q3W 4 cycles d1 and d8 IV Q3W 5 cycles + + Clinical stage T2-T4aN0M0 or Pembrolizumab 200 mg d1 Pembrolizumab 200 mg d1 T1-T4aN1M0 by central assessment R 1:1 IV Q3W 4 cycles Urothelial histology ≥50% Eligible for RC + PLND Cisplatin 70 mg/m² d1 IV Q3W 4 cycles RC + PLND IV Q3W 13 cycles Did not meet any Galsky criteria for + Observationᵇ cisplatin ineligibility N = 403 Gemcitabine 1000 mg/m² ECOG PS 0-1 d1 and d8 IV Q3W 4 cycles Stratification Factors PD-L1 status (CPS ≥10 vs. <10)a Primary endpoint: Event-free survival (EFS) by BICR Clinical stage (T2N0 vs. T3/T4aN0 VS. T1-4aN1) Key secondary endpoints: OS and pathological complete response (pCR; pTONO, i.e. absence of viable tumor in examined tissue from surgery) by central pathologist review Geographic region (US vs. EU VS. Most of World) Other secondary endpoints include: Safety BICR, blinded independent central review; CPS, combined positive score; IV, intravenous; Q3W, every 3 weeks. "Assessed by PD-L1 IHC 22C3 pharmDx (Agilent, Carpinteria, CA); CPS = # PD-L1-staining cells (tumor cells, lymphocytes, and macrophages) + total # viable tumor cells x 100. As of Feb 2023, adjuvant nivolumab was permitted when clinically indicated and regionally available. Data cutoff date: 27 October 2025 --- [Slide 2] Primary Endpoint: EFS by BICR ITT Population EV + pembro Cis + gem N = 405 N = 403 100 Events, n (%) 87 (21.5) 146 (36.2) 90 86.0% 79.4% Median, mo (95% CI) NR (NR-NR) 48.5 (43.3-NR) 80 Event-free survival, % 70 60 75.4% 66.2% 50 40 30 20 HR 0.53, 95% CI 0.41-0.70, 1-sided P <.0001* 10 0 0 6 12 18 24 30 36 42 48 54 Months No. at Risk EV + pembro 405 351 317 303 257 154 100 63 23 0 Cis + gem 403 350 286 259 216 131 70 45 16 0 Data cutoff date: 27 October 20 not reached. . denotes statistical significance (one-sided boundary 0.0082). --- [Slide 3] Key Secondary Endpoint: OS ITT Population 100 93.1% 86.9% 90 80 89.6% 70 81.3% Overall survival, % 60 50 EV + pembro Cis + gem N = 405 N = 403 40 Events, n (%) 69 (17.0) 99 (24.6) 30 Median, mo (95% CI) NR (NR-NR) NR (NR-NR) 20 HR 0.65, 95% CI 0.48-0.89, 10 1-sided P =.0029* 0 0 6 12 18 24 30 36 42 48 54 Months No. at Risk EV + pembro 405 396 377 361 325 215 142 90 34 0 Cis + gem 403 392 358 338 295 201 119 67 29 0 In total, 44/87 (50.6%) of pts with an EFS event in the EV + pembro arm and 86/146 (58.9%) of pts with an EFS event in the cis + gem arm received any subsequent systemic therapy Data cutoff date: 27 October 2025 NR, not reached. . denotes statistical significance (one-sided boundary 0.0038). --- [Slide 4] Key Secondary Endpoint: pCR by Central Pathology Review ITT Population 100 Estimated differenceᵃ 23.4% (95% CI 16.7-29.8) EV + pembro Cis + gem N = 405 N = 403 1-sided P <.0001* 80 pCR, n 226 131 pCR, % (95% CI) 60 H pCR rate, % 55.8 32.5 (95% CI) (50.8-60.7) (28.0-37.3) 40 H pCR: defined as absence of viable tumor in examined tissue from RC + PLND (pTONO) 20 Pts who discontinued study therapy prior to definitive surgery were classified as non-responders 0 Out of pts who underwent surgery, 226/351 (64.4%) in the EV + Cis + EV + pembro arm and 131/361 (36.3%) in the cis + gem pembro gem arm had pCR * denotes statistical significance (one-sided boundary 0.001). Data cutoff date: 27 October 202 "Based on stratified Miettinen and Nurminen method.

[Slide 1] des 21 21 2026 2026 2026 GUCANCERS ... do MVOID+ TOPICS TRENDING --- [Slide 2] Patient population: Primary endpoints eligible MIBC Durva+GC arm Neoadjuvant Adjuvant EFS* (cT2-T4aN0/1M0) n=533 Durva 1500 mg IV Durvalumab 1500 mg IV pCR' UC or UC with divergent differentiation or histologic subtypes Gemcitabine+Cisplatin Q4W, 8 cycles Key secondary endpoint CrCl of >40 mL/min Q3W, 4 cycles os R RC Secondary endpoints Stratification: 1:1 MFS Clinical tumour stage (T2N0 vs >T2N0) Renal function (CrCl 260 mL/min vs >40- N=1066 DSS Gemcitabine+cisplatin No treatment <60 mL/min) n=530 Safety PD-L1 status (high vs low/negative Immune-mediated AEs GC comparator arm expression) Patient population: EV+pembro arm Adults with MIBC EV 1.25 mg/kg EV 1.25 mg/kg Clinical stage T4aNOMC or 11 T4aN1M0 by n=405 01 and D8 IV Q3W 4 cycles Primary endpoint D1 and D8 IV Q3W5 cycles central EFS** Urothelial histology 250% Pembro 200 mg D1 Pembro 200 mg D1 Eligible of PLND Key secondary endpoints IV Q3W 4 cycles Did not meet any Galsky criteria for cisplatin ineligibility PLND IV Q3W 13 cycles ECOG PS0-1 R os 1:1 Cisplatin 70 mg/m2 pCR" Stratification: 01 IV Q3W 4 cycles Safety PO-L1 status (CPS is <10)* N=808 + Observation Clinical stage (T2ND as T3/T4aND n 71-4aN1) n=403 Gemcitabine 1000 mg/m2 Immune-mediated AEs Geographic region (USA vs tu 93 Most of the World) GC arm D1 and D8 IV Q3W 4 cycles Patient population: Neoadjuvant Adjuvant Arm A MIBC cT2-T4aN0- P (n=210) Pembro Q3W x 3 cycles Pembro Q3W X 14 cycles 1M0 or cT1-4aN1M0 Primary endpoint: Ineligible for EFS P+EV VS observation cisplatin KN-905/ Cis-refusal Arm B R Observation Cystectomy Secondary endpoints: Observ Observation' EV-303⁴ 1:1 EFS P VS observation Stratification: N=344 Tumour stage OS, pCR, DFS, pDS, safety Cis-ineligible vs Arm C Pembro Q3W X 3 cycles Pembro Q3W X 14 cycles and tolerability cis-refusal P+EV - EV Q3W X 3 cycles EV Q3W X 6 cycles --- [Slide 3] Can ctDNA guide adjuvant immunotherapy after NAC or in cis-ineligible patients? IMvigor011 study design Surveillance Screening Treatment Follow-up ctDNA monitoring until 1 y post-cystectomy* Atezolizumab (1680 mg) IV q4w for up to 1y MIBC within 6-24 weeks of Confirm no evidence of R Treatment radical cystectomy radiographic disease 2:1 follow-up Placebo Histologically confirmed IV q4w for up to y (y)pT2-T4aNOMO or 6-weekly ctDNA+ (y)pTO-T4aN+M0 ctDNA testing any time urothelial cancer No evidence of 12-weekly radiographic disease radiographic ctDNA- imaging until 1y Prior neoadjuvant chemotherapy permitted No treatment Surveillance ECOG PS 0-2 follow-up Repeat testing if ctDNA- Primary endpoint: INV-assessed DFS Key secondary endpoint: OS Powles T, et al. NEJM 2025

[Slide 1] Galsky KNB15 ASCO GU 2026 ASCO Genitourinary Cancers Symposium Neoadjuvant and Adjuvant Enfortumab Vedotin Plus Pembrolizumab for Participants With Muscle-Invasive Bladder Cancer Who Are Eligible for Cisplatin: Randomized, Open-Label, Phase 3 KEYNOTE-B15 Study Matthew D. Galsky1, Begoña Pérez-Valderrama², Marco Maruzzo³, Albert Font4, Tudor Ciuleanu⁵, Jonathan Chatzkel⁶, Takuya Koie⁷, Christopher Hoimes⁸, Javier Puente⁹, Yousef Zakharia¹⁰, Eli Rosenbaum¹¹, Katharina Boehm¹², Yohann Loriot¹³, Jens Bedke¹⁴, Thomas B. Powles¹⁵; Heidi S. Wirtz¹⁶, Michael Mihm17, Qinlei Huang¹⁸, Aljosja Rogiers¹⁸, Blanca Homet Moreno¹⁸, Alfonso Gómez de Liaño19 11cahn School of Medicine at Mount Sinai, Tisch Cancer Institute, New York, NY, USA; 2Hospital Universitario Virgen del Rocio, Seville, Spain; 31stituto Oncologico Veneto IRCCS-Oncologia Medica 1. Padova, Italy: Catalan Institute of Oncology (ICO) Badalona, Barcelona, Spain; 5Institutul Oncologic Prof. Dr. on Chiricuta Cluj-Napoca, Cluj-Napoca, Romania; University of Florida, Gainesville, FL, USA; [current affiliation] Moffitt Cancer Center, Tampa, FL, USA; Gifu University Hospital, Gifu, Japan; Duke University Medical Center, Durham, NC, USA; Hospital Clinico Universitario San Carlos de Madrid, Madrid, Spain; 10Mayo Clinic, Phoenix, AZ, USA; "Rabin Medical Center-Oncology, Petah Tikva, Israel; 12University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany, 13Institut Gustave Roussy, Université Paris-Saclay, Villejuif, France; 14Eva Mayr-Stihl Cancer Center, Klinikum Stuttgart, Stuttgart, Germany; 15Barts Health NHS Trust and the Royal Free NHS Foundation Trust, Barts Cancer Institute, and Queen Mary University of London, London, United Kingdom; "Pfizer, Bothell, WA, USA; 17Astellas Pharma Inc. Northbrook, IL, USA; 18Merck & Co., Inc., Rahway, NJ, USA; 19Complejo Hospitalario Universitario Insular-Materno Infantil de Gran Canaria, Las Palmas, Spain ASCO Genitourinary #GU26 PRESENTED BY: Matthew D. Galsky ASCO AMERICAN SOCIETY OF CLINICAL ONCOLOGY Cancers Symposiu Presentation is property of the author and ASCO Permission required for reuse, contact permissions@asco.org KNOWLEDGE CONQUERS CANCER CC ... --- [Slide 2] Galsky KNB15 ASCO GU 2026 KEYNOTE-B15/EV-304 Study (NCT04700124) Key Eligibility Criteria Enfortumab vedotin 1.25 mg/kg Enfortumab vedotin 1.25 mg/kg Adults with MIBC N = 405 d1 and d8 IV Q3W 4 cycles d1 and d8 IV Q3W 5 cycles + + Clinical stage T2-T4aNOM0 or Pembrolizumab 200 mg d1 Pembrolizumab 200 mg d1 T1-T4aN 1M0 by central assessment R 1:1 IV Q3W 4 cycles Urothelial histology ≥50% Eligible for RC + PLND Cisplatin 70 mg/m2 RC + PLND IV Q3W 13 cycles d1 IV Q3W4 cycles Did not meet any Galsky criteria for + Observationᵇ cisplatin ineligibility N = 403 Gemcitabine 1000 mg/m2 ECOG PS 0-1 d1 and d8 IV Q3W 4 cycles Stratification Factors PD-L1 status (CPS ≥10 VS. <10)ᵃ Primary endpoint: Event-free survival (EFS) by BICR Clinical stage (T2N0 VS. T3/T4aN0 VS. T1-4aN1) Key secondary endpoints: OS and pathological complete response (pCR; pTONO, i.e. absence of viable tumor in examined tissue from surgery) by central pathologist review Geographic region (US vs. EU VS. Most of World) Other secondary endpoints include: Safety BICR, blinded independent central review; CPS, combined positive score; IV, intravenous; Q3W, every 3 weeks. *Assessed by PD-L1 IHC 22C3 pharmDx (Agilent, Carpinteria, CA); CPS = # PD-L1-staining cells (tumor cells, lymphocytes, and macrophages) - total # viable tumor cells X 100. As of Feb 2023, adjuvant nivolumab was permitted when clinically indicated and regionally available. Data cutoff date: 27 October 2025 --- [Slide 3] Galsky KNB15 ASCO GU 2026 Primary Endpoint: EFS by BICR ITT Population EV + pembro Cis + gem N = 405 N = 403 100 Events, n (%) 87 (21.5) 146 (36.2) 90 86.0% 79.4% Median, mo (95% CI) NR (NR-NR) 48.5 (43.3-NR) 80 Event-free survival, % 70 60 75.4% 66.2% 50 40 30 20 HR 0.53, 95% CI 0.41-0.70, 1-sided P <.0001* 10 0 0 6 12 18 24 30 36 42 48 54 Months No. at Risk EV + pembro 405 351 317 303 257 154 100 63 23 0 Cis + gem 403 350 286 259 216 131 70 45 16 0 Data cutoff date: 27 October 2025 NR. not reached . denotes statistical significance (one-sided boundary 0.0082). --- [Slide 4] Galsky KNB15 ASCO GU 2026 Key Secondary Endpoint: OS ITT Population 100 93.1% 86.9% 90 80 89.6% 70 81.3% Overall survival, % 60 50 EV + pembro Cis + gem N = 405 N = 403 40 Events, n (%) 69 (17.0) 99 (24.6) 30 Median, mo (95% CI) NR (NR-NR) NR (NR-NR) 20 HR 0.65, 95% CI 0.48-0.89, 10 1-sided P =.0029* 0 0 6 12 18 24 30 36 42 48 54 Months No. at Risk EV + pembro 405 396 377 361 325 215 142 90 34 0 Cis + gem 403 392 358 338 295 201 119 67 29 0 In total, 44/87 (50.6%) of pts with an EFS event in the EV + pembro arm and 86/146 (58.9%) of pts with an EFS event in the cis + gem arm received any subsequent systemic therapy Data cutoff date: 27 October 2025 NR. not reached. . denotes statistical significance (one-sided boundary 0.0038).

[Slide 1] KEYNOTE-B15/EV-304 Study (NCT04700124) Key Eligibility Criteria Enfortumab vedotin 1.25 mg/kg Enfortumab vedotin 1.25 mg/kg Adults with MIBC N = 405 d1 and d8 IV Q3W 4 cycles d1 and d8 IV Q3W 5 cycles + + Clinical stage T2-T4aN0M0 or Pembrolizumab 200 mg d1 Pembrolizumab 200 mg d1 T1-T4aN1M0 by central assessment R 1:1 IV Q3W 4 cycles Urothelial histology >50% Eligible for RC + PLND Cisplatin 70 mg/m2 d1 IV Q3W 4 cycles RC + PLND IV Q3W 13 cycles Did not meet any Galsky criteria for + Observation cisplatin ineligibility N = 403 Gemcitabine 1000 mg/m2 ECOG PS 0-1 d1 and d8 IV Q3W 4 cycles Stratification Factors PD-L1 status (CPS ≥10 vs. <10)a Primary endpoint: Event-free survival (EFS) by BICR Clinical stage (T2N0 vs. T3/T4aN0 vs. T1-4aN1) Key secondary endpoints: OS and pathological complete response (pCR; pTONO, i.e. absence of viable tumor in examined tissue from surgery) by central pathologist review Geographic region (US vs. EU VS. Most of World) Other secondary endpoints include: Safety BICR, blinded independent central review; CPS, combined positive score; IV, intravenous; Q3W, every 3 weeks. "Assessed by PD-L1 IHC 22C3 pharmDx (Agilent, Carpinteria, CA); CPS = # PD-L1-staining cells (tumor cells, lymphocytes, and macrophages) + total # viable tumor cells X 100. As of Feb 2023, adjuvant nivolumab was permitted when clinically indicated and regionally available. Data cutoff date: 27 October 2025 --- [Slide 2] Primary Endpoint: EFS by BICR ITT Population EV + pembro Cis + gem N = 405 N = 403 100 Events, n (%) 87 (21.5) 146 (36.2) 90 86.0% 79.4% Median, mo (95% CI) NR (NR-NR) 48.5 (43.3-NR) 80 Event-free survival, % 70 60 75.4% 66.2% 50 40 30 20 HR 0.53, 95% CI 0.41-0.70, 1-sided P <.0001* 10 0 0 6 12 18 24 30 36 42 48 54 Months No. at Risk EV + pembro 405 351 317 303 257 154 100 63 23 0 Cis + gem 403 350 286 259 216 131 70 45 16 0 Data cutoff date: 27 October 2025 NR, not reached. * denotes statistical significance (one-sided boundary 0.0082). --- [Slide 3] EFS by BICR in Key Subgroups ITT Population Events/Participants EV + pembro Cis + gem HR (95% CI) Overall 87/405 146/403 0.53 (0.41-0.70) Age <65 years 24/158 51/156 0.43 (0.27-0.70) >65 years 63/247 95/247 0.59 (0.43-0.82) Sex Male 69/327 113/327 0.56 (0.42-0.76) Female 18/78 33/76 0.47 (0.26-0.83) Race White 73/329 119/314 0.53 (0.40-0.71) All others 14/76 27/87 0.53 (0.28-1.01) Region United States 8/59 14/59 0.58 (0.25-1.39) European Union 48/206 86/205 0.47 (0.33-0.68) Most of world 31/140 46/139 0.65 (0.41-1.02) PD-L1 CPS ≥10 43/233 74/230 0.53 (0.36-0.77) <10 43/171 72/173 0.54 (0.37-0.79) Tumor stage by BICR T2N0 15/79 19/77 0.76 (0.39-1.51) T3/T4aN0 65/293 110/293 0.54 (0.40-0.73) T1-4aN1 7/33 17/33 0.30 (0.12-0.72) 0.05 0.25 0.5 1.0 2.0 4.0 Favors EV + pembro Favors cis + gem Data cutoff date: 27 October 2025 bgroup levels with <10 events across both treatment arms were not included in forest plots. --- [Slide 4] Key Secondary Endpoint: OS ITT Population 100 93.1% 86.9% 90 80 89.6% 70 81.3% Overall survival, % 60 50 EV + pembro Cis + gem N = 405 N = 403 40 Events, n (%) 69 (17.0) 99 (24.6) 30 Median, mo (95% CI) NR (NR-NR) NR (NR-NR) 20 HR 0.65, 95% CI 0.48-0.89, 10 1-sided P =.0029* 0 0 6 12 18 24 30 36 42 48 54 Months No. at Risk EV + pembro 405 396 377 361 325 215 142 90 34 0 Cis + gem 403 392 358 338 295 201 119 67 29 0 In total, 44/87 (50.6%) of pts with an EFS event in the EV + pembro arm and 86/146 (58.9%) of pts with an EFS event in the cis + gem arm received any subsequent systemic therapy Data cutoff date: 27 October 2025 not reached. . denotes statistical significance (one-sided boundary 0.0038).