KEYNOTE-905 Trial

[Slide 1] Bladder Preservation pCR rates are outstanding MIBC Likely to see significant practice swings 20 ASCO"Genitourinary toward bladder preservation 26 Cancers Symposium We are in the wild west until we get data Bladder Cystectomy Preservation Che XRT ?NAC + Cher XRT ChemoXRT 0? Cis-eligible Cis-ineligible GC-Durva GC/DDMVAC +> GC/DDMVAC + EV/Pembro Adjuvant IO for Ct-Guided EV/Pembro (NIAGRA) Adjuvant IO for Ct-Guided High Risk2 Adjuvant 103 (KN-B15)⁵ High Risk2 Adjuvant 103 (KN-905)⁴ OS @ 2 years: OS @ 2 years: OS @ 2 years: EFS @ 2 years: OS @ 2 years: OS @ 2 years: EFS @ years: 82% vs 75% 76% vs 70% 63% vs 47% 79% vs 66% 76% vs 70% 63% vs 47% 75% vs 40% +7% +6% +16%* +13% +6% +16%* +35% os @ 2 years: OS @ 2 years: "ctDNA positive only 87% vs 81% "ctDNA positive only 80% vs 63% +6% +17% Powles et at N Engl Med 2024 Nov 14,391(19) 1773-1786 Galsky J Clin Oncol 43, 15-21(2025) Powles N Engl Med 2025 Dec 18,393(24) 2395-2408; "Vulsteke ESMO 2025; "Galsky GU ASCO 2026 ASCO Genitourinary #GU26 PRESENTED BY Tyler F. Stewart, MD ASCO AMERICAN CURICAL INCOLOGY Cancers Symposium Presentation property author and ASCO Permission required for - contact permasions@asco.org KNOWLEDGE CONQUERS CANCER ASCO Genitourinary Cancers Symposium --- [Slide 2] EV/P for Everyone? Nectin4 20 ASCO® Genitourinary 26 Cancers Symposium Worldwide context Trop2 Her2 Accessibility Cost ADCs in SLITRK6 Bladder HER3 Cancer Histologic variants? Tissue Factor EpCam What happens if they progress shortly after EV/P? B7H3 EV/P is the new starting point, it's not the end ASCO Genitourinary #GU26 PRESENTED BY Tyler F. Stewart, MD ASCO AMERICAN SOCIETY OF CURRENCE Cancers Symposium Presentation property of the author and ASCO Permission required for - contact permissions@asco.org KNOWL EDGE CONQUERS CANCER ASCO Genitourinary Cancers Symposium --- [Slide 3] EFS and OS across MIBC Trials 20 ASCO"Genitourinary 26 Cancers Symposium 2 Year EFS 2 Year os 100 100 87 90 90 82 80 81 80 80 75 70 79 75 70 63 60 68 66 60 % 50 60 % 50 40 40 30 39 30 20 20 10 10 0 0 GC GC-durva No chemo EVP GC EVP GC GC-durva No chemo EVP GC EVP NIAGRA KN-905 KN-B15 NIAGRA KN-905 KN-B15 2y EFS 2y OS HR 0.68 HR 0.53 HR 0.75 HR 0.65 @ median 42 months @ median 33 months @ R median 46 months @ median 33 months Powles of al N Engl Med 2024 Nov 14,391(19) 1773-1786 Galsky J Clin Oncol 43, 15-21(2025) N Engl Med 2025 Dec 18,393(24) 2395-2408 "Vulsteke ESMO 2025; "Galsky GU ASCO 2026 ASCO Genitourinary #GU26 PRESENTED BY: Tyler F. Stewart, MD ASCO AMERICAN SOCIETY or CURICAL SHICOLOGY Cancers Symposium Presentation property the author and ASCO Permission required for - contait permissions@asco.org KNOWLEDGE CONQUERS CANCER ASCO Genitourinary Cancers Symposium --- [Slide 4] Complete Pathologic Response Across Trials Pathologic Complete Rate Across MIBC Trials 100 20 ASCO"Genitourinary 26 Cancers Symposium 100 Estimated differenceᵃ 90 23.4% (95% CI 16.7-29.8) 1-sided P <.0001* 80 80 70 56% Of those who pCR, % (95% CI) 60 57 60 underwent 56 surgery: * 50 33% 64% vs 36% 42 40 40 37 36 37 33 30 26 20 20 15 9 10 0 0 EV + Cis + No chemo MVAC GC ddMVAC GC GC-durva No chemo EVP GC EVP pembro gem GROSSMAN VESPER NIAGRA KN-905 KN-B15 Powles of al N Engl Med 2024 Nov 14,391(19) 1773-1786 Vulsteke ESMO 2025; Galsky GU ASCO 2025; Grossman N Engl J Med 2003 Aug 28,349(9) 859-66; Pfister / Clin Oncol 2022 Jun 40(18)2013-2022 ASCO Genitourinary #GU26 PRESENTED BY Tyler F. Stewart, MD ASCO AMERICAN SOCIETY CUPICAL ONCOLOGY Cancers Symposium Presentation property of the author and ASCO Permission required for - contact permissions@asco.org KNOWLEDGE CONQUERS CANCER ASCO Genitourinary Cancers Symposium

[Slide 1] Abstract #638, ASCO Genitourinary Cancer Symposium 2026 Pathological outcomes and disease-free survival (DFS) in KEYNOTE-905: Neoadjuvant and adjuvant (neoadj- adj) enfortumab vedotin (EV) plus pembrolizumab (pembro) in participants (pts) with muscle-invasive bladder cancer (MIBC) who are cisplatin-ineligible Anders Ullén, Christof Vulsteke, Jens Bedke, Steffen Rausch, Shilpa Gupta, Seok-Ho Kang, Jeanny B. Aragon-Ching, Laura Bernal Vaca, Viktor Paramonov, Avivit Peer, Viktor Stus, Vagif Atduev, Keita Nakane, Jasmine Lichfield, Changting Meng, David Huang, Chethan Ramamurthy, Blanca Homet Moreno, Matthew D. Galsky @neerajaiims --- [Slide 2] Abstract #638, ASCO Genitourinary Cancer Symposium 2026 Pathological outcomes and disease-free survival (DFS) in KEYNOTE-905: Neoadjuvant and adjuvant (neoadj-adj) enfortumab vedotin (EV) plus pembrolizumab (pembro) in participants (pts) with muscle- invasive bladder cancer (MIBC) who are cisplatin-ineligible Presenting Author: Anders Ullén Neoadjuvant phase Adjuvant phase Patient population Pembrolizumab (n 870) 200 mg Q3W IV + Pembrolizumab Eligible for treatment with Gemcitabine 1000 mg/m2 200 mg Q3W IV cisplatin and Cisplatin 70 mg/m2 x13 cycles Histologically confirmed Q3W x4 cycles MIBC with predominant urothelial histology and Posttreatment PD-L1 expression follow-up will (CPS ≥10 or CPS <10) Clinically nonmetastatic bladder cancer (N â 1MO) Stratification R RC + PLND assess: Event-free survival 1:1 Overall survival Eligible for radical Safety cystectomy and pelvic PROs lymph node dissection No prior systemic anti-neoplastic treatment Placebo + for MIBC Gemcitabine 1000 mg/m2 Placebo Received TURBT and Cisplatin 70 mg/m2 ECOG performance x13 cycles Q3W x4 cycles status 0 or 1 End points Primary: pCR, EFS Key secondary: OS, DFS, pDS, PROs, safety and tolerability Exploratory: biomarkers @neerajaiims --- [Slide 3] Abstract #638, ASCO Genitourinary Cancer Symposium 2026 Pathological outcomes and disease-free survival (DFS) in KEYNOTE-905: Neoadjuvant and adjuvant (neoadj-adj) enfortumab vedotin (EV) plus pembrolizumab (pembro) in participants (pts) with muscle- invasive bladder cancer (MIBC) who are cisplatin-ineligible Presenting Author: Anders Ullén Results: N; % (95% CI) EV + pembro, N=170 Control, N=174 pDS (<pT2N0) 112 65.9 (58.2-73.0) 22 12.6 (8.1-18.5) pTONO 97 57.1 (49.3-64.6) 15 8.6 (4.9-13.8) pTisN0 7 4.1 (1.7-8.3) 2 1.1 (0.1-4.1) pTaN0 1 0.6 (0.0-3.2) 0 0.0 (0.0-2.1) pT1N0 7 4.1 (1.7-8.3) 5 2.9 (0.9-6.6) Non-pDS (≥pT2N0) 33 19.4 (13.8-26.2) 112 64.4 (56.8-71.5) Other* 2 1.2 (0.1-4.2) 15 8.6 (4.9-13.8) Incomplete resection 2 1.2 (0.1-4.2) 7 4.0 (1.6-8.1) Did not undergo surgery 21 12.4 (7.8-18.3) 18 10.3 (6.2-15.9) *Not evaluated centrally for pDS due to no available evaluable surgical sample, non-protocol systemic therapy prior to RC + PLND or operational issues; considered non-pDS in analysis. Conclusion: pCR, pDS, surgical outcomes, and DFS favored neoadj-adj EV + pembro and RC + PLND VS RC + PLND alone, supporting the primary results of KEYNOTE-905. These findings further establish neoadj-adj EV + pembro as a potential standard of care for pts with MIBC who are cisplatin-ineligible, addressing a key unmet clinical need. @neerajaiims

[Slide 1] EFS and OS across MIBC Trials 2 Year EFS 2 Year os 100 100 87 90 90 82 80 81 80 80 75 70 79 75 70 63 60 68 66 60 % 50 60 % 50 40 40 30 39 30 20 20 10 10 0 0 GC GC-durva No chemo EVP GC EVP GC GC-durva No chemo EVP GC EVP NIAGRA KN-905 KN-B15 NIAGRA KN-905 KN-B15 2y EFS B 2y OS HR 0.68 HR 0.53 HR 0.75 HR 0.65 @ median 42 months @ median 33 months @ median 46 months @ median 33 months Powles et al N Engl J Med. 2024 Nov 14,391(19): 1773-1786; 2Galsky Clin Oncol 43, 15-21(2025); N Engl J Med. 2025 Dec 18,393(24) 2395-2408 Vulsteke ESMO 2025; "Galsky GU ASCO 2026 ASCO Genitourinary #GU26 PRESENTED BY: Tyler F. Stewart, MD ASCO AMERICAN SOCIETY OF CLINICAL ONCOLOGY Cancers Symposium Presentation is property of the author and ASCO Permission required for reuse, contact permissions@asco.or KNOWLEDGE CONQUERS CANCER --- [Slide 2] How many cycles of EV/P? Not answered by Is the Adjuvant Portion Necessary? these studies GC/Durva Durva NIAGRA MIBC R GC EV/D D VOLGA MIBC R EV/D/T D/T EV/P X 3 EV/P X 6 KN-905 MIBC R EV/P X 4 EV/P X 5 Future studies necessary to define the KN-B15 MIBC R role of adjuvant portion GC ASCO Genitourinary #GU26 PRESENTED BY: Tyler F. Stewart, MD Cancers Symposium ASCO AMERICAN GOOETY OF CUPICAL ONCOLOGY Presentation a property of the author and ASCO Permission required for reuse, contact permissions@asco.org KNOWLEDGE CONQUERS CANCER --- [Slide 3] Preservation ChemoXRT ?NAC ChemoXRT ChemoXRT + 10? Cis-ineligible Adjuvant IO for Ct-Guided EV/Pembro High Risk2 Adjuvant 103 (KN-905)4 @ 2 years: os @ 2 years: 76% vs 70% 63% vs 47% +6% +16%* "CEDNA positive only 95-2408; Vuistake ESMO 2025 ASCO AMERICAN SOCUTION CUPICAL provide KNOWLEDGE CONQUERS CANCER 1 --- [Slide 4] EFS and OS across MIBC Trials 2 Year EFS 2 Year os 100 100 87 90 90 82 80 81 80 80 75 70 79 75 70 63 60 68 66 60 % 50 60 % 50 40 40 30 39 30 20 20 10 10 0 0 GC GC-durva No chemo EVP GC EVP GC GC-durva No chemo EVP GC EVP NIAGRA KN-905 KN-B15 NIAGRA KN-905 KN-B15 2y EFS B 2y OS HR 0.68 HR 0.53 HR 0.75 HR 0.65 @ median 42 months @ median 33 months @ median 46 months @ median 33 months Powles et al N Engl J Med. 2024 Nov 14,391(19): 1773-1786; 2Galsky Clin Oncol 43, 15-21(2025); N Engl J Med. 2025 Dec 18,393(24) 2395-2408 Vulsteke ESMO 2025; "Galsky GU ASCO 2026 ASCO Genitourinary #GU26 PRESENTED BY: Tyler F. Stewart, MD ASCO AMERICAN SOCIETY OF CLINICAL ONCOLOGY Cancers Symposium Presentation is property of the author and ASCO Permission required for reuse, contact permissions@asco.or KNOWLEDGE CONQUERS CANCER --- [Slide 5] Treatment for MIBC MIBC Cis-Gem GUASCO Bladder Cystectomy Preservation ChemoXRT ?NAC +> ChemoXRT ChemoXRT + 10? Cis-eligible Cis-ineligible GC-Durva GC/DDMVAC GC/DDMVAC EV/Pembro Adjuvant 10 for (NIAGRA)1 Adjuvant O for Ct-Guided Ct-Guided EV/Pembro High Risk2 Adjuvant 103 (KN-B15)⁵ High Risk2 Adjuvant 103 (KN-905)4 OS @ 2 years: OS @ 2 years: OS @ 2 years: EFS @ 2 years: OS @ 2 years: OS @ 2 years: EFS @ years: 82% VS 75% 76% VS 70% 63% VS 47% 79% vs 66% 76% VS 70% 63% vs 47% 75% vs 40% +7% +6% +16%* +13% +6% +16%* +35% OS @ 2 years: "ctDNA positive only 87% vs 81% OS @ 2 years: "ctDNA positive only 80% vs 63% +6% Powles et al N Engl Med. 2024 Nov 14,391(19) 1773-1786; 2Galsky Clin Oncol 43, 15-21(2025); Powles N Engl Med. 2025 Dec 18,393(24) 2395-2408 "Vulsteke ESMO 2025; Galsky GU ASCO 2026 +17% ASCO Genitourinary Cancers Symposium #GU26 PRESENTED BY: Tyler F. Stewart, MD ASCO AMERICAN SOCIETY OF Presentation is property of the author and ASCO Permission required for reuse, contact permissions@asco.org CUNICAL ONCOLOGY KNOWLEDGE CONQUERS CANCER --- [Slide 6] How many cycles of EV/P? Not answered by Is the Adjuvant Portion Necessary? these studies GC/Durva Durva NIAGRA MIBC R GC EV/D D VOLGA MIBC R EV/D/T D/T EV/P X 3 EV/P X 6 KN-905 MIBC R EV/P X 4 EV/P X 5 Future studies necessary to define the KN-B15 MIBC R role of adjuvant portion GC ASCO Genitourinary #GU26 PRESENTED BY: Tyler F. Stewart, MD Cancers Symposium ASCO AMERICAN GOOETY OF CUPICAL ONCOLOGY Presentation a property of the author and ASCO Permission required for reuse, contact permissions@asco.org KNOWLEDGE CONQUERS CANCER

[Slide 1] Conclusions Pathological outcomes and DFS favored neoadjuvant-adjuvant enfortumab vedotin + pembrolizumab and RC + PLND compared with RC + PLND alone, supporting the primary results of KEYNOTE-9051 - Negative surgical margins: 92.6% versus 78.8% - pCR rate: 57.1% VS 8.6%; estimated difference 48.3% (CI, 39.5-56.5; P <.001), generally consistent across subgroups - pDS rate: 65.9% VS 12.6%; estimated difference 53.1%; (CI, 44.0-61.2) - DFS: median DFS NR versus 23.6 months (HR 0.37; CI, 0.23-0.59) Per previous reports, the safety profile of neoadjuvant-adjuvant enfortumab vedotin + pembrolizumab was manageable and consistent with that of this regimen in the locally advanced/metastatic urothelial carcinoma setting¹ These findings further establish neoadjuvant-adjuvant enfortumab vedotin + pembrolizumab as a standard-of-care treatment option for patients with MIBC who are cisplatin ineligible, addressing a key unmet clinical need 1. Vulsteke C, et al. Ann Oncol. 2025; Volume 36 (Supplement 2):S1648. Data cutoff date: June 6, 2025. --- [Slide 2] KEYNOTE-905/EV-303 Study (NCT03924895) Allocation to this treatment arm stopped Nov 2022 Key Eligibility Criteria Adults with MIBC Pembrolizumab 200 mg IV Q3W 3 cycles Pembrolizumab 200 mg Clinical stage T2-T4aNOMO IV Q3W 14 cycles or T1-T4aN1M0 by central assessment R n 174 R 1:1 >50% urothelial histology N : 344 Cisplatin ineligible or Enfortumab vedotin 1.25 mg/kg RC + PLND Observation® cisplatin declining n : 170 d1 and d8 IV Q3W 3 cycles Enfortumab vedotin 1.25 mg/kg ECOG PS score 0-2 + d1 and d8 IV Q3W 6 cycles Pembrolizumab 200 mg IV Q3W 3 cycles Pembrolizumab 200 mg Stratification Factors IV Q3W 14 cycles Cisplatin ineligibility End points (ineligible VS eligible but Primary: EFS by BICR declining) Key secondary: OS Clinical stage (T2N0 VS T3/T4aN0 VS T1-4aN1) Region (US VS EU VS most Other secondary: Pathologic complete response (pCR; absence of viable tumor in tissue from RC + PLND [pTONO[)= of world) Disease-free survival (DFS; time from post-surgery scan to localidistant recurrence or death) Pathologic downstaging (pDS; <pT2 (pTO, pTis, pTa, pT1] and NO in tissue from RC + PLND) Protocol New BICR, York blinded defined Heart independent Association; as central 21 OS, of overall review; survival; d, day; PLND, ECOG pelvic PS, Eastern ymph Cooperative node dissection; Oncology Q3W, Group every performance 3 weeks; R, randomization; status; EFS, event-free RC, radical survival; N, intravenous MBC, muscle-invasive bladder cancer, NYMA, As of November 2022, having adjuvant nivolumab the following: impaired renal function (creatinine clearance, 30 to 59 mL/min), ECOG PS score 2, CTCAE 4 cystectomy grade 22 they had complete resection (no gross residual was disease) permitted and when no evidence clinically of indicated disease and on a regionally post-surgery available. scan Assessed by central pathology or BICR Participants audometric were hearing considered oss, or NYHA doease-free Class after If heart RC alue PLND I 20 ASCO Genitourinary 26 Cancers Symposium --- [Slide 3] pDS by BICR in the ITT Population 100 EV + Pembro Control n (CI), % Estimated difference (n = 170) (n=174) 53.1% (CI, 44.0-61.2) 80 pDS (<pT2N0) 112 65.9(58.2-73.0) 22 12.6(8.1-18.5) pTONO 97 57.1(49.3-64.6) 15 8.6(4.9-13.8) pTisN0 7 4.1(1.7-8.3) 2 1.1 (0.1-4.1) pDS, % (95% CI) 60 pTaNO 1 0.6 (0.0-3.2) 0 0.0(0.0-2.1) pT1N0 7 4.1(1.7-8.3) 5 2.9(0.9-6.6) 40 Non-pDS (2pT2N0) 33 19.4(13.8-26.2) 112 64.4 (56.8-71.5) Incomplete 20 2 resection 1.2(0.1-4.2) 7 4.0(1.6-8.1) No surgery 21 12.4 (7.8-18.3) 18 10.3(6.2-15.9) 65.9% 12.6% 0 Other 2 1.2(0.1-4.2) 15 8.6(4.9-13.8) EV + Control Pembro Not evaluated centrally for pDS due to no available evaluable surgical sample, nonprotocal systemic therapy prior to RC * PLND, or operational issues; considered non-pOS in analysis, Data cutoff date: June 6, 2025. 20 ASCO Genitourinary 26 Cancers Symposium --- [Slide 4] Conclusions Pathological outcomes and DFS favored neoadjuvant-adjuvant enfortumab vedotin + pembrolizumab and RC + PLND compared with RC + PLND alone, supporting the primary results of KEYNOTE-9051 - Negative surgical margins: 92.6% versus 78.8% - pCR rate: 57.1% VS 8.6%; estimated difference 48.3% (CI, 39.5-56.5; P <.001), generally consistent across subgroups - pDS rate: 65.9% VS 12.6%; estimated difference 53.1%; (CI, 44.0-61.2) - DFS: median DFS NR versus 23.6 months (HR 0.37; CI, 0.23-0.59) Per previous reports, the safety profile of neoadjuvant-adjuvant enfortumab vedotin + pembrolizumab was manageable and consistent with that of this regimen in the locally advanced/metastatic urothelial carcinoma setting¹ These findings further establish neoadjuvant-adjuvant enfortumab vedotin + pembrolizumab as a standard-of-care treatment option for patients with MIBC who are cisplatin ineligible, addressing a key unmet clinical need 1. Vulsteke C, et al. Ann Oncol. 2025; Volume 36 (Supplement 2):S1648. Data cutoff date: June 6, 2025. --- [Slide 5] Disease-Free Survival by BICRᵃ EV + Pembro Control 100 (n = 135) (n. : 129) 90 84.9% 83.2% Events, n (%) 26 (19.3) 57 (44.2) 80 Median (CI), mo NR (NR-NR) 23.6 (13.7-NR) Disease-Free Survival, % HR (CI) 0.37 (0.23-0.59) 70 62.0% 60 49.6% 50 40 30 20 10 0 0 6 12 18 24 30 36 42 48 54 60 Months No. at Risk EV + pembro 135 115 75 58 43 36 18 5 0 0 0 Control 129 98 57 38 27 16 12 6 1 0 0 HR, hazard ratio; NR, not reached Participants were considered disease-free after RC . PLND for DFS analysis if they had complete resection (no gross residual disease) and no evidence of disease on a post-surgery scan. Based on Cox regression model with the Efron method of tie handling with treatment as a covariate. Data culoff date: June 6, 2025. Genitourinary