CheckMate-274 Trial

[Slide 1] Benefit vs Overtreatment - MIBC Cohort NIVOLUMAB PLACEBO Patients with Patient is already Recurred cured benefit from Recurred Patient is already cured at 3 years nivolumab = adjuvant nivo at 3 years does not need treatment overtreatment Total pts 53% 15% 32% Total pts 68% 32% 281 279 ASCO Genitourinary CHECKMATE 274 Milowsky et al. ASCO GU 2025 #GU25 ASCO AMERICAN SOCIETY OF PRESENTED BY: Elizabeth Plimack, MD MS FASCO CLINICAL ONCOLOGY Cancers Symposium Presentation * property of the author and ASCO Permission required for reuse, contact permissions@asco.org KNOWLEDGE CONQUERS CANCER --- [Slide 2] For Checkpoint inhibitors - persistent PD1 receptor occupancy suggests that effects of NAC extend into the adjuvant period even without adjuvant dosing 300 100 100 80 80 [MDX-1106] (ug/mL) 200 60 10 mg/kg (n = 10) 40 100 PD-1 Occupancy (%) PD-1 Occupancy (%) Pt. 4033 60 40 [MDX-1106] (ug/mL) KX PD-1 occupancy (%) 20 20 0 0 20 40 60 80 0 100 200 300 400 500 600 Time (days) Time (days) One dose of nivolumab saturates PD1 receptors out beyond 3 mo With 3 doses of nivolumab even as drug itself is cleared PD1 receptors remain occupied (40%) at ~380 days from last dose ASCO Genitourinary Brahmer et al., Phase I study of single-agent anti- #GU25 PRESENTED BY: ASCO AMERICAN SOCIETY OF Elizabeth Plimack, MD MS FASCO CLINICAL ONCOLOGY Cancers Symposium programmed death-1 (MDX-1106) in refractory Presentation . property of the author and ASCO Permission required for reuse, contact permissions@asco.org KNOWLEDGE CONQUERS CANCER solid tumors. J Clin Oncol 28, 3167-3175 (2010) --- [Slide 3] NIAGARA in the context of currently available treatment options NIAGARA VESPER COXEN Durvalumab 90% N=533 Durvalumab Gem Cis X 4 Gem Cis x 4 R Gem Cis Cystectomy x8mo MIBC R 1:1 N 437pts Cystectomy MIBC R MIBC Gem Cis ddMVAC X 6 N 227pts Cystectomy No treatment ddMVAC X 4 N=530 91% DGC "sandwich" VS GC ddMVAC VS GC ddMVAC VS GC EFS benefit at 2 yrs: 8% EFS benefit at 5 yrs: 9% EFS benefit at 5 yrs: 4% OS benefit at 2 yrs: 7% OS benefit at 5 yrs: 9% OS benefit at 5 yrs: 7% Differences were not statistically significant 60% 55% COXEN 52% ddMVAC 46% 50% VESPER 41% 41% 40% 37% Age Range, Median DurvaGC NIAGARA 30% 20% NIAGARA 10% GC COXEN 0% VESPER Rate of Grade 3/4 TRAE ddMVAC DurvaGC GC 30 40 50 60 70 80 90 VESPER range provided by C Culine/VESPER team Age (years) NIAGARA COXEN VESPER Age range was previously reported as 95% CI ASCO Genitourinary NIAGARA Galsky et al. ASCO GU 2025 #GU25 PRESENTED BY: Elizabeth Plimack, MD MS FASCO ASCO AMERICAN SOCIETY OF CLINICAL ONCOLOGY Cancers Symposium Pfister et al. The Lancet Onc 25, 255-264 (2024). Presentation is property of the author and ASCO Permission required for reuse, contact permissions@asco.org KNOWLEDGE CONQUERS CANCER Flaig et al. Eur Urol 84, 341-347 (2023). --- [Slide 4] NIAGARA in the context of currently available treatment options NIAGARA VESPER COXEN Durvalumab 90% N=533 Durvalumab Gem Cis X 4 Gem Cis X 4 R Gem Cis Cystectomy X 8 mo MIBC R 1:1 N 437pts Cystectomy MIBC R MIBC Gem Cis ddMVAC X 6 N 227pts Cystectomy No treatment ddMVAC X 4 N=530 91% DGC "sandwich" VS GC ddMVAC VS GC ddMVAC VS GC EFS benefit at 2 yrs: 8% EFS benefit at 5 yrs: 9% EFS benefit at 5 yrs: 4% OS benefit at 2 yrs: 7% OS benefit at 5 yrs: 9% OS benefit at 5 yrs: 7% Differences were not statistically significant 100% 100% 80% 80% Path Complete Response ypTONO rate 60% 2 year Overall Survival 60% 40% 2-year OS rate 40% 20% 20% 32% 42% 37% 28% 34% 36% 82% 83% 82% 75% 77% 78% 0% 0% ddMVAC DurvaGC GC ddMVAC DurvaGC GC NIAGARA COXEN VESPER NIAGARA COXEN VESPER ASCO Genitourinary NIAGARA Galsky et al. ASCO GU 2025 #GU25 PRESENTED BY: Elizabeth Plimack, MD MS FASCO ASCO AMERICAN SOCIETY OF CLINICAL ONCOLOGY Cancers Symposium Pfister et al. The Lancet Onc 25, 255-264 (2024). Presentation is property of the author and ASCO Permission required for reuse, contact permissions@asco.org KNOWLEDGE CONQUERS CANCER Flaig et al. Eur Urol 84, 341-347 (2023).

[Slide 1] ASCO Genitourinary Abstract 658 Cancers Symposium Adjuvant nivolumab (NIVO) vs placebo (PBO) for high-risk muscle-invasive urothelial carcinoma (MIUC): Additional efficacy outcomes including overall survival (OS) in patients (pts) with muscle- invasive bladder cancer (MIBC) from CheckMate 274. Authors: Matthew I. Milowsky & Matthew D. Galsky et al. os Trends Favor NIVO vs. PBO Background: All MIBC: NR vs. 39.9 months (HR 0.70 [0.55-0.90]) CheckMate 274 showed adjuvant nivolumab (NIVO) improves DFS in PD-L1 ≥ 1%: NR vs. 37.6 months (HR 0.48 [0.29-0.77]) high-risk muscle-invasive urothelial carcinoma (MIUC). With prior NAC: 55.2 vs. 40.2 months (HR 0.74 [0.53-1.03]) *With 3-year median follow-up, further analyses explore overall Without prior NAC: NR vs. 37.7 months (HR 0.67 [0.47-0.95]) survival (OS) in muscle-invasive bladder cancer (MIBC). Safety Profile: Objective: Assess DFS & os in MIBC patients, including PD-L1+ and Consistent with prior data; no new safety signals. prior NAC subgroups. Conclusion: Key Results (N=560 MIBC patients, Median FU: 36.1 months) NIVO continues to demonstrate DFS and os benefit in MIBC, Disease-Free Survival (DFS) Benefit with NIVO vs. Placebo (PBO) including PD-L1+ and prior NAC subgroups. All MIBC: 25.6 vs. 8.5 months (HR 0.63 [0.51-0.78]) These results reinforce adjuvant NIVO as the standard of care for *With prior NAC: 19.6 vs. 8.3 months (HR 0.58 [0.43-0.79]) high-risk MIUC and MIBC. Without prior NAC: 25.9 vs. 13.7 months (HR 0.69 [0.50-0.94]) Potentially curative option for patients post-radical surgery. X @nataliagandur @drnataliagandur GANDUR

[Slide 1] 2 --- [Slide 2] pCR vs non-pCR OS data should not be extrapolated to support contribution of adjuvant 1.0 pCR 95.5% Absolute 2 year OS in 0.8 91.1% pCR group - 4% non-pCR Probability of survival 0.6 Benefit may all be from 74.1% durable receptor 04 68.9% occupancy, or more durable IO response to the neoadjuvant 0.2 Durvalumab am component compared Comparator am with GC alone 0 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 54 56 58 60 62 64 68 No of patients X nex Time from randomization (months) Dam 199 199 157 154 194 194 193 192 190 189 189 189 189 187 186 185 154 176 164 149 139 129 111 95 83 68 54 44 31 14 11 2 0 0 Cam 146 145 145 144 144 143 142 140 139 137 136 134 133 133 132 130 130 124 117 109 100 93 85 76 65 51 40 31 23 15 7 3 0 0 Dam 334 329 320 311 298 284 275 265 256 251 245 239 234 231 224 223 215 199 185 172 156 142 127 112 99 84 71 52 37 20 10 5 1 0 Cam 384 370 361 346 323 307 296 285 274 255 256 249 245 240 236 233 228 210 154 172 159 146 130 118 109 90 73 59 37 23 14 7 2 0 ASCO Genitourinary NIAGARA Galsky et al. ASCO GU 2025 Cancers Symposium #GU25 PRESENTED DY Elizabeth Plimack, MD MS FASCO ASCO AMERICAN SOCIETY or CUNICAL CHICOLOGY Presentation . property IF the author and ASCO Permission required - - contact generag KNOWLEDGE CONQUERS CANCER --- [Slide 3] CheckMate 274 OSᵃ: all randomized patients with MIBC 100 Median OS (95% CI), months 90 NIVO NR (45.0-NE) 80 75.3% PBO 39.9 (29.8-52.1) HR (95% CI), 0.70 (0.55-0.90) Overall survival probability (%) 70 64.2% 60 66.2% 50 53.7% 40 30 20 10 0 0 6 12 18 24 30 36 42 48 54 60 66 72 78 Months No. at risk NIVO 279 258 239 213 193 172 145 107 81 56 34 20 3 0 PBO 281 240 218 195 172 143 119 89 65 43 31 17 6 0 "Interim OS analysis. Median follow-up of 36.1 months in the ITT population and 34.5 months in the MIBC population. Galsky MD, et al. J Clin Oncol 2025;43:15-21. --- [Slide 4] Take Home: 2 options for clinic on Monday Neoadjuvant ddMVAC "Sandwich" Approach with GC Durva 25% 25% Metastatic Metastatic ZypT2 35% 75% 75% Met Met <ypT2 65% free at free at 2 years 2 years Neoadj ddMVAC Observation Neoadj Gem Cis + Durva Durvalumab X 8 Benefits of risk adapted approach using ddMVAC Benefits of a "sandwich" approach - ZypT2 35% patients would qualify for and may gain - If using Gem Cis, adding durvalumab pre and post additional benefit from adjuvant nivolumab or the adds benefit in direct and cross trial comparison MODERN trial - Adjuvant durvalumab may benefit some of the ~10% - Avoids overtreatment and IO toxicity for <ypT2 65% of <ypT2 who develop metastases but would not - Cost and time saving have qualified for adjuvant nivolumab NIAGARA Galsky et at. ASCO GU 2025 ASCO Genitourinary #GU25 PRESENTED EX Elizabeth Plimack, MD MS FASCO VESPER Pfister et at. LBA4507, ASCO 2023 ASCO AMERICAN SOCIETY OF CLINICAL CHICOLOGY Cancers Symposium Presentation . property of the author and ASCO Permission request Rar - contact permissions@amin.org S Culine and VESPER team personal communication KNOWLEDGE CONQUERS CANCER

[Slide 1] 08:15 - 08:25 GMT-8 + ABSTRACT PRESENTATION 1 Adjuvant nivolumab (NIVO) vs placebo (PBO) for high-risk muscle-invasive urothelial carcinoma (MIUC): Additional efficacy outcomes including overall survival (OS) in patients (pts) with muscle-invasive bladder cancer (MIBC) from CheckMate 274. Abstract 658 Matthew I. Milowsky, MD, FASCO University of North Carolina School of Medicine --- [Slide 2] Results: Of 709 randomized pts (ITT), 560 (79%) had MIBC (NIVO, n = 279; PBO, n = 281); 284 (51%) of MIBC pts had prior NAC. With median follow-up of 36.1 mo (ITT), DFS improvement with NIVO vs PBO was consistent between all pts with MIBC (hazard ratio [HR] 0.63) and those with (HR 0.58) and without prior NAC (HR 0.69; Table). For OS, HRs favored NIVO vs PBO in all pts with MIBC (HR 0.70) and the tumor PD-L1 ≥ 1% subgroup (HR 0.48), as well as in pts with MIBC with (HR 0.74) and without prior NAC (HR 0.67). Safety was consistent with previous data in ITT pts; no new safety signals were identified. --- [Slide 3] Conclusions: With 3-y median follow-up, consistent benefit in DFS was observed with NIVO vs PBO in all MIBC pts and across prior NAC subgroups. The HR for os favored NIVO in all MIBC pts, in those with PD- L1 ≥ 1%, and regardless of prior NAC status. These results continue to support adjuvant NIVO as a standard of care for high-risk MIUC and MIBC, potentially providing an opportunity for a curative outcome.

[Slide 1] Comparison of Adjuvant Regimens for Cancer (Intent to Treat vs Placebo) Absolute DFS Absolute OS Trial Benefit Benefit ADAURA NSCLC (EGFRmut) 41% 12% https://ascopubs.org/doi/pdf/10.1200/ICO 22.02186 https://www.neim.org/doi/ful/10.1056/NEJMoa2304594 Bladder Cancer 15% 11% CHECKMATE 274 Milowky et al.ASCO GU 2025 Breast (TN) 9% 8% KEYNOTE-522 https://www.nejm.org/doi/full/10.1056/NEJMoa2409932 Breast (HER2+) 14% 5% KATHERINE https://www.neim.org/doi/full/10.1056/NEJMoa2406870 RCC 8% 5% KEYNOTE-564 https://dol.org/10.1056/NEJMoa2312695 Melanoma 14% Awaiting events KEYNOTE-054 Expected at year 10 https://pubmed.ncbi.nlm.nih.gov/39288737/ Colorectal Cancer 6% 3% MOSAIC NSCLC 8% 2% KEYNOTE 091 https://doi.org/10.1016/S1470-2045(22)00518-6 NSCLC 6% 1% IMPower010 https://ascopubs.org/doi/10.1200/CO.2024.42.17_suppl.LBA8035 Breast (HR+) 7% 1% MonarchE https://doi.org/10.1200/ICO.23.01994 ASCO Genitourinary #GU25 PRESENTED BY: ASCO AMERICAN SOCIETY Of Elizabeth Plimack, MD MS FASCO CLINICAL ONCOLOGY Cancers Symposium Presentation 10 property of the author and ASCO. Permission required for reuse; contact parmissions@asco.org KNOWLEDGE CONQUERS CANCER