POTOMAC Trial

[Slide 1] POTOMAC: Study Design Durvalumab 1500 mg IV (Q4W X 13 cycles) Primary endpoint D+BCG (I+M) BCG Maintenance Study population N=339 BCG Induction DFS: D+BCG (I+M) vs BCG (I+M) 3 weekly doses at Age ≥18 years Weekly x 6 weeks 3m 6m 12m 18m 24m NMIBC Secondary endpoints BCG-naive 5-year OS rate High-risk tumor defined Durvalumab 1500 mg IV (Q4W X 13 cycles) (data cutoff 03 October 2025) R D+BCG as any of the following: Patient-reported outcomes (1:1:1) (I only) T1 BCG Induction N=1018 (data cutoff 03 April 2025) N=339 High-grade/G3 Weekly x 6 weeks" CIS Multiple and recurrent and large (≥3 cm) BCG (I+M) BCG Maintenance N=340 BCG Induction 3 weekly doses at Weekly X 6 weeks" 3m 6m 12m 18m 24m Stratification factors: First patient enrolled: June 2018 Higher-risk papillary disease (T1G3/T1 high-grade or multiple and recurrent and large tumors) Last patient enrolled: October 2020 CIS Last D dose: January 2022 Last BCG dose: January 2023 De Santis M, et al Lancet 2025;406.2221-2234 All disease assessments were performed by the investigator For patients with persistent CIS disease at 3 months, a single BCG res induction was administered weekly for 6 weeks according to local standard practice BCG, bacillus Calmette- Guérin; CIS, carcinoma in situ: D. durvalumab DFS, disease free survival; G, grade; 1, induction; IV, intravenous; m, month; 2026 ASCO #ASCO26 M. maintenance, OS, overall survival; NMIBC, muscle invasive bladder cancer, Q4W, every 4 weeks; R, randomization ASCO AMERICAN SOCIETY OF CLINICAL ONCOLOGY ANNUAL MEETING Presentation is property of the author and ASCO Permission required for reuse, contact permissions@asco.org KNOWLEDGE CONQUERS CANCER --- [Slide 2] POTOMAC: 5-Year Overall Survival - ITT No detriment at the 5-year OS analysis was observed with the addition of durvalumab to BCG (I+M) therapy D+BCG (I+M) BCG (I+M) N=339 N=340 Deaths, n (%) 45 (13) 56 (16) Median OS NR NR 1.0 88% (95% CI), months (NR-NR) (NR-NR) 0.8 86% Probability of OS 0.6 0.4 HR 0.81 (95% CI, 0.54-1.19) 0.2 Median follow-upᵃ: 72 months 0 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66 69 72 75 78 81 84 87 90 Time from randomization (months) No. of patients at risk D+BCG (I+M) 339 336 329 326 324 320 319 315 314 311 306 303 298 296 293 290 290 286 283 277 270 236 217 182 141 115 73 30 11 1 0 BCG (I+M) 340 338 336 333 330 328 326 322 317 313 313 313 309 305 301 295 292 288 284 281 275 239 220 185 140 108 70 32 12 0 0 in censored patients across treatment arms Data cutoff 03 October 2025. OS is the time from randomization until death due to any cause regardless of whether the patient withdraws from randomized therapy or receives another anti-cancer therapy BCG, bacillus Calmette-Guérin CI, confidence interval; D, durvalumab; HR hazard ratio, I, induction ITT, intent to treat population; M, maintenance NR, not reached; OS, 2026 ASCO #ASCO26 overall survival ASCO AMERICAN SOCIETY OF CLINICAL ONCOLOGY ANNUAL MEETING Presentation is property of the author and ASCO Permission required for reuse, contact permissions@asco.org KNOWLEDGE CONQUERS CANCER --- [Slide 3] POTOMAC: EORTC QLQ-C30 Change From Baseline Adjusted mean changes from baseline showed modest deterioration in GHS/QoL and physical functioning and increased fatigue in both treatment arms, with generally similar changes between treatment arms GHS/QoL1 Physical Functioning Fatigue Difference between arms: -2.7 (95% CI, -4.85 to -0.54) Difference between arms: -2.6 (95% CI, -4.43 to -0.81) Difference between arms: 4.0 (95% CI, 1.50 to 6.46) 20 20 20 Adjusted mean change 10 from baseline Better Worse -20 Adjusted mean change 10 from baseline Better 0 Adjusted mean change 10 Worse 0 -10' from baseline 0 -10 Worse -10 Better -20 -20 2 10 18 26 34 42 50 58 66 74 82 90 98 106114122130138146 2 10 18 26 34 42 50 58 66 74 82 90 98 106 2 10 18 26 34 42 50 58 66 74 82 90 98 106114122130138146 Visit (weeks) Visit (weeks) Visit (weeks) No of patients in analysis No of patients in analysis No of patients in analysis D+BCG (I+M)214 202 189 180 177 174 171 156 149 142 148 135 138 130 126 122 117 104 105 D+BCG (I+M)214 202 189 180 177 174 171 156 149 142 148 138 138 130 126 122 117 104 105 D+BCG (1+M)214 202 189 180 177 174 171 156 149 142 148 138 138 130 126 122 117 104 105 BCG (I+M)232 219 213 192 193 178 183 158 165 165 158 149 152 138 139 133 120 124 123 BCG (I+M)232 219 213 192 193 178 183 158 165 165 158 149 152 138 139 133 120 124 123 BCG (I+M)232 219 213 192 193 178 183 158 165 165 158 149 152 138 139 133 120 124 123 Clinically meaningful change from baseline 1. De Santis M, of al Lancet 2025:406 2221-2234 Data cutoff 03 April 2025 Decreases indicate worsening for GHS/QoL and physical functioning; increases indicate worsening for fatigue Error bars show 95% CI Change from baseline was analyzed using mixed model for repeated measures and heterogenous Toeplitz, with stratification factors, treatment, visit, baseline score treatment by-visit and baseline score- by-visit interactions as explanatory variables Only patients with an evaluable baseline score and at least evaluable postbaseline score are included in the analysis model A clinically meaningful change was defined as a 10 point change in score compared with baseline. BCG, bacillus Calmette-Guérin CFB, change from baseline, CI, confidence interval, D. durvalumab; EORTC QLQ-C30 European Organisation for 2026 ASCO #ASCO26 Research and Treatment of Cancer 30 item core quality of life questionnaire GHS/QoL global health scale/quality of Me, I, induction, M, maintenance ASCO AMERICAN SOCIETY OF CLINICAL ONCOLOGY ANNUAL MEETING Presentation is property of the author and ASCO Permission required for reuse; contact permissions@asco.org KNOWLEDGE CONQUERS CANCER --- [Slide 4] POTOMAC PRO-CTCAE Symptoms PRO-CTCAE Symptom Worsening on Treatment Through Week 106 Abdominal pain 76% (39/51) D+BCG (I+M) (Interference) 68% (40/59) BCG (I+M) Across abdominal pain, diarrhea, and Abdominal pain 67% (162/241) painful urination, rates of PRO-CTCAE (Frequency) 63% (156/246) worsening were similar between treatment Abdominal pain 59% (30/51) arms through Week 106, consistent with the (Severity) 63% (37/59) shared BCG treatment backbone Diarrhea 60% (144/241) (Frequency) For urinary frequency, rates of PRO-CTCAE 65% (159/246) worsening were numerically higher with Painful urination 83% (200/241) D+BCG (80%) VS BCG (73%), with a (Severity) 82% (201/246) difference ≤10% Urinary frequency 79% (127/160) (Interference) 69% (125/181) Urinary frequency 80% (193/241) (Frequency) 73% (179/246) 0 20 40 60 80 100 Patients with any worsening (%)a Data cutoff 03 April 2025 Patients with increased PRO CTCAE score during treatment/patients with baseline and at least 1 on treatment PRO CTCAE assessment BCG, bacillus Calmette-Guérin, 2026 ASCO #ASCO26 D, durvalumab; I, induction, M. maintenance, PRO CTCAE, patient reported outcomes version of the Common Terminology Criteria for Adverse Events ASCO AMERICAN SOCIETY OF CUNICAL ONCOLOGY ANNUAL MEETING Presentation is property of the author and ASCO Permission required for reuse, contact permissions@asco.org KNOWLEDGE CONQUERS CANCER

[Slide 1] POTOMAC: EORTC QLQ-C30 Change From Baseline Adjusted mean changes from baseline showed modest deterioration in GHS/QoL and physical functioning and increased fatigue in both treatment arms, with generally similar changes between treatment arms 2026ASCO ANNUAL MEETING GHS/QoL' Physical Functioning Fatigue Difference between arms -27 (95% CL,-4,85 10-0.54) Difference between arms -2.5 (95% CL -4.4310-0.81) Difference between arms: 4.0 (95% CL 1.50 to 6.46) 2026 ASCO #ASCO26 ASCO ANNUAL MEETING CONDUERS CANCER --- [Slide 2] POTOMAC: EORTC QLQ-NMIBC24 Change From Baseline Adjusted mean change-from-baseline scores were not clinically meaningful and were similar between treatment arms Urinary Symptoms Intravesical Treatment Issues Difference between ams for overall mean 1.2 Difference between ams for overal mean CFB-1.2(0% CL-3.79 1o1.29) I - Future Perspective/Worries Sexual Functioning Difference between arms for overall mean CFB-22 (90% CL, -5.11 10 0.66) Difference between am for overal mean CFB - Val. I Clarically meaningful change baseline Data - Email tan Change for have - analyzed - - expeated - Toxpito - - baseline of interactions - explanatory I I with taxine the analysis defined . 10-port I compand with I below Guara CFS, I confidence 2026 ASCO #ASCO26 Company Organisation I - ASCO ANNUAL MEETING KNOWLEDGE CONQUERS --- [Slide 3] POTOMAC PRO-CTCAE Symptoms PRO-CTCAE Symptom Worsening on Treatment Through Week 106 Abdominal pain 76% (39/51) D+BCG (I+M) (Interference) 68% (40/59) BCG (I+M) Across abdominal pain, diarrhea, and Abdominal pain 67% (162/241) painful urination, rates of PRO-CTCAE (Frequency) 63% (156/246) worsening were similar between treatment Abdominal pain 59% (3051) arms through Week 106, consistent with the (Severity) 63% (37/59) shared BCG treatment backbone Diarrhea 60% (144/241) For urinary frequency, rates of PRO-CTCAE (Frequency) 65% (159/246) worsening were numerically higher with Painful urination 83% (200/241) D+BCG (80%) VS BCG (73%), with a (Severity) 82% (201/246) difference <10% Urinary frequency 79% (127/160) (Interference) 69% (125/181) Urinary frequency 80% (193/241) (Frequency) 73% (179/246) 0 20 40 60 80 100 Patients with any worsening (%)* Date - April with nonumed - during Insurrent/pations - BOG tacks - 2026 ASCO #ASCO26 D. aduction, M. mankmance PRO-CTCAL patient autoomes - the Common lemecks or Advote Events ASCO ANNUAL MEETING KNOWLEDGE CONQUERS CANCER --- [Slide 4] POTOMAC: Conclusions At the planned 5-year OS analysis, the addition of durvalumab to 2026ASCO BCG (I+M) continued to show no detriment to OS (HR 0.81; 95% CI, ANNUAL MEETING 0.54-1.19) from the The addition of durvalumab to BCG (I+M) did not have a major Plan impact on patient-reported quality of life, with generally similar PROs between treatment arms These data further support 1 year of durvalumab in combination with BCG induction and maintenance as a new treatment for patients with BCG-naïve, high-risk NMIBC 1 De M. a code - I - . name 2026 ASCO #ASCO26 patient ASCO ANNUAL MEETING

[Slide 1] POTOMAC: Study Design Durvalumab 1500 mg IV (Q4W X 13 cycles) Primary endpoint D+BCG (I+M) BCG Maintenance Study population N=339 BCG Induction DFS: D+BCG (I+M) vs BCG (I+M) 3 weekly doses at Age ≥18 years Weekly X 6 weeks 3m 6m 12m 18m 24m NMIBC Secondary endpoints BCG-naive 5-year OS rate High-risk tumor defined Durvalumab 1500 mg IV (Q4W X 13 cycles) (data cutoff 03 October 2025) R D+BCG as any of the following: Patient-reported outcomes (1:1:1) (I only) T1 BCG Induction N=1018 (data cutoff 03 April 2025) N=339 High-grade/G3 Weekly X 6 weeks CIS Multiple and recurrent and large (>3 cm) BCG (I+M) BCG Maintenance N=340 BCG Induction 3 weekly doses at Weekly X 6 weeks 3m 6m 12m 18m 24m Stratification factors: First patient enrolled: June 2018 Higher-risk papillary disease (T1G3/T1 high-grade or multiple and recurrent and large tumors) Last patient enrolled: October 2020 CIS Last D dose: January 2022 Last BCG dose: January 2023 De Santis M, of al. Lancet 2025,406,2221-2234 All disease assessments were performed by the investigator For patients with persistent CIS disease at 3 months, a single BCG re-induction was administered weekly for 6 weeks according to local standard practice BCG, bacillus Calmette-Guerin; CIS, carcinoma in situ; D, durvalumab; DFS, disease-free survival; G, grade; I, induction; IV, intravenous; m, month; 2026 ASCO #ASCO26 M, maintenance; OS, overall survival; NMIBC, non-muscle-invasive bladder cancer, Q4W, every 4 weeks; R, randomization ASCO AMERICAN SOCIETY OF CUMICAL ONCOLOGY ANNUAL MEETING Presentation is property of the author and ASCO. Permission required for reuse, contact permissions@asco. org. KNOWLEDGE CONQUERS CANCER --- [Slide 2] POTOMAC: EORTC QLQ-C30 Change From Baseline Adjusted mean changes from baseline showed modest deterioration in GHS/QoL and physical functioning and increased fatigue in both treatment arms, with generally similar changes between treatment arms GHS/QoL1 Physical Functioning Fatigue Difference between arms: -2.7 (95% CI, -4.85 to -0.54) Difference between arms: -2.6 (95% CI, -4.43 to -0.81) Difference between arms: 4.0 (95% CI, 1.50 to 6.46) 20 20 20 Adjusted mean change 10 Better from baseline -10 Adjusted mean change 10 Better 0 from baseline Adjusted mean change 10 0 Worse from baseline Worse 0 Worse -10 -10 Botter -20 -20 -20 2 10 18 26 34 42 50 58 66 74 82 90 98 106114122130138146 2 10 18 26 34 42 50 58 66 74 82 90 98 106114122130138146 2 10 18 26 34 42 50 58 66 74 82 90 98 106114122130138146 Visit (weeks) Visit (weeks) Visit (weeks) No. of patients in analysis No of patients in analysis No. of patients in analysis D+BCQ (1+88)214 189 180 177 174 171 156 149 142 148 138 138 130 126 122 117 104 105 D+BCG (1+81)214 202 189 180 177 174 171 156 149 142 148 138 138 130 126 122 117 104 105 D+BCG (I+M)214 202 189 180 177 174 171 156 149 142 148 138 138 130 126 122 117 104 105 BCG (+M)232 213 192 193 178 183 158 165 165 158 149 152 138 139 133 120 124 123 BCG (1+18)232 219 213 192 193 178 183 158 165 165 158 149 152 138 139 133 120 124 123 BCQ (1+M) 219 213 192 193 178 183 158 165 165 158 149 152 138 139 133 120 124 123 Clinically meaningful change from baseline 1. De Santis M, of al. Lancet 2025,406,2221-2234 Data cutoff 03 April 2025 Decreases indicate worsening for GHS/QoL and physical functioning: increases indicate worsening for fatigue. Error bara show 95% CI. Change from baseline was analyzed using a mixed model for repeated measures and heterogenous Toeplitz, with stratification factors, treatment, visit, baseline score, treatment-by-visit and baseline score- by-visit interactions as explanatory variables. Only patients with an evaluable baseline score and at least 1 evaluable postbaseline score are included in the analysis model A clinically meaningful change was defined as a 10-point change in score compared with baseline. BCG, bacillus Calmette-Guérin, CFB, change from baseline; CL, confidence interval; D, durvalumab; EORTC QLQ-C30, European Organisation for 2026 ASCO Research and Treatment of Cancer 30-item core quality of life questionnaire; GHS/QoL. global health scale/quality of life; I, induction; M, maintenance #ASCO26 ASCO AMERICAN SOCIETY OF CLINICAL ONCOLOGY ANNUAL MEETING Presentation is property of the author and ASCO. Permission required for reuse, contact permissions@asco.org KNOWLEDGE CONQUERS CANCER --- [Slide 3] POTOMAC: EORTC QLQ-NMIBC24 Change From Baseline Adjusted mean change-from-baseline scores were not clinically meaningful and were similar between treatment arms Urinary Symptoms Intravesical Treatment Issues Difference between arms for overall mean CFB:1.2 (95% CI,-1.19 to 3.65) Difference between arms for overall mean CFB:-1.2 (95% CI, -3.79 to 1.29) 20 20 10 10 Adjusted mean change Worse from baseline 0 Beter Adjusted mean change Worse from baseline 0 Better -10 -10 -20 -20 10 14 18 22 21 # | M 30 42 41 30 54 - 42 " 70 N 78 82 N to # 102 126112 14 122 5 130 134 138142 45 100 : 10 14 18 22 26 30 H 42 54 14 42 06 79 74 78 #2 - 90 94 - 192 106110 114 14 (26 (30 42 100 Visit (weeks) in pateris analysis No - analysis Visit (weeks) program 196 190 177 180 62 IS4 153 ISS 190 145 148 134 143 $45144 144 or - 132 25 127 126 124 100 243 221 195 - - 149 148 - 1 in (21 200 241 Future Perspective/Worries Sexual Functioning Difference between arms for overall mean CFB:-2.2 (95% CI, -5.11 to 0.66) Difference between arms for overall mean CFB: 1.1 (95% CI, -1.30 to 3.48) 20 20 10 10 Adjusted mean change Worse from baseline 10 Adjusted mean change from baseline Beter 0 0 Better Worse -10 -20 -20 14 " 25 30 34 # 42 48 so $4 - u " to N 76 # " N M 16 102 105 10 = 122 129 130 134 138142 145 150 2 10 14 18 22 25 30 24 a 42 44 to $4 sa = " N 78 " # 90 M " 102 105 114 118 122 125 130 134 138142 145 Visit (weeks) to - analysis No - analysis Visit (weeks) pregar F96 180 107 154 10 154 160 149 148 154 43 E 137 (27 129 122 127 FOR 195 190 177 160 167 164 158 560 135 BCG Clinically meaningful change from baseline Data cutoff 03 April 2025 Error bars show 95% CI Change from baseline was analyzed using mixed model for repeated measures and heterogeneous Toeplitz, with stratification factors, treatment, visit, baseline score, treatment by visit, and baseline score by visit interactions as explanatory variables. Only patients with an evaluable baseline score and at least 1 evaluable postbaseline score are included in the analysis model A clinically meaningful change was defined as a 10 point change in score compared with baseline BCG, bacillus Calmette-Guérin; CFB, change from baseline; CI, confidence interval; 0, 2026 ASCO #ASCO26 durvalumab; EORTC QLQ-NMIBC24, European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Non-Muscle-Invasive Bladder Cancer 24; I, induction; M, maintenance ASCO AMERICAN SOCIETY or CLINICAL ONCOLOGY ANNUAL MEETING Presentation is property of the author and ASCO Permission required for reuse, contact permissions@asco.org. KNOWLEDGE CONQUERS CANCER --- [Slide 4] Key Takeaway Points In the POTOMAC study, the addition of durvalumab to BCG (I+M) continued to show no OS detriment at the planned 5-year OS analysis Durvalumab in combination with BCG (I+M) did not have a major impact on patient-reported quality of life 2026 ASCO BCG, Bacillus Calmette-Guerin I, induction; M, maintenance OS, overall survival. #ASCO26 ASCO AMERICAN SOCIETY OF CLINICAL ONCOLOGY ANNUAL MEETING Presentation is property of the author and ASCO Permission required for reuse; contact permissions@asco.org KNOWLEDGE CONQUERS CANCER

[Slide 1] POTOMAC: Study Design Durvalumab 1500 mg IV (Q4W . 13 cycles) Study population D+BCG (I+M) BCG Maintenance N=339 BCG Induction Age 2 18 years 3 weekly doses at Weekly * 6 weeks NMIBC 3m 6m 12m 18m 24m BCG-naive High-risk tumor Durvalumab 1500 mg IV (Q4W - 13 defined as any of R D+BCG cycles) the following: (1:1/1) (I only) N=1018 BCG Induction T1 N=339 Weekly * 6 weeks High-grade/G3 CIS Multiple and recurrent and BCG (I+M) BCG Maintenance large (23 cm) N=340 BCG Induction 3 weekly doses at Weekly * 6 weeks 3m 6m 12m 18m 24m Stratification factors: . Postio Higher-risk papillary disease (T1G3/T1 high-grade or multiple and recurrent and --- [Slide 2] POTOMAC: EORTC QLQ-C30 Change From Baseline Adjusted mean changes from baseline showed modest deterioration in GHS/QoL and physical functioning and increased fatigue in both treatment arms, with small differences between treatment arms GHS/QoL' Physical Functioning Fatigue D+BCG (1+M) -76 (95% CI, -9.19 to -6.07) D+BCG (I+M): -5.5 (95% CL -6.76 to -4.15) D+BCG (I+M): 10.1 (95% CI, 8.32 32 to 11.90) BCG (I+M): -4.9 (95% CI, -6.46 to -3.41) BCG (1+M): -28 (95% CL -4.11 -4.11to-1.56) BCG (I+M): 6.1 (95% CI, 4.37 to 7.88) Difference between arms: -2.7 (95% CI, -4.85 to -0.54) Difference between arms: =2.6 (95% CI, -4.43 to -0.81) Difference between arms: 4.0 (95% CL 1.50 to 6.46) 20 20 20 Address change I St I I Befor Adjusted I I 2 Deber -10 -10 licre I I I 10 Work D 0 Worse I benefine 1 0 -10 Better -20 & 8 2 10 18 X 34 42 56 56 74 12 90 M 2 NO 14 X 34 42 50 58 66 74 12 to 2 10 . 28 34 42 50 50 56 T4 82 XI Visit [weeks] Visit (weeks) Valt [weeks] No of justerns . anarysis No or patients if anarysis No. if (satents if anarysis Cirically meaninglu change from baseline --- [Slide 3] POTOMAC: PRO Questionnaire Compliance and Baseline Scores Baseline questionnaire completion rate was high. Similar baseline PRO scores between treatment arms were observed, indicating high QoL and physical functioning and low symptom burden (eg, fatigue) at study entry Absolute baseline PRO scoresᵇ D+BCG (I+M) BCG (I+M) Compliance N=339 N=340 EORTC QLQ-C30 D+BCG 100 EORTC QLQ-C30 (I+M) 80 Baseline assessment completed 74% 79% Mean score at baseline 60 40 Baseline and >1 post-baseline assessment 72% 75% 20 completed 0 GHS/QoL Physical Fatigue Compliance rate range 50%-82% 56%-84% functioning (baseline - Week 138ᵃ) EORTC QLQ-NMIBC24 EORTC QLQ-NMIBC24 100 80 Baseline assessment completed 80% 82% Baseline and >1 post-baseline assessment 78% 80% Mean score at baseline 60 40 completed 20 0 Compliance rate range 50%-87% Urinary Intravesical Future perspective/ Sexual 56%-86% (baseline - Week 142ᵃ) symptoms treatment issues worries functioning --- [Slide 4] Frequency of toxicity with adjuvant immune checkpoint inhibition in RCC according to patient defined framework LC Adjuvant immune therapy Life changing Frequency of patient-defined categories SLT in IMmotion010 atezolizumab arm (n=262) Endocrine Significant long term LC Adrenal insufficiency/Hypophysitis 12% Insulin dependent diabetes Rheumatological Chronic toxicity requiring - ≥3 Arthritis/Myositis/Vasculitis SLT Steroids Cardiopulmonary NS 22% - Admission to hospital - ≥3 Pneumonitis/Myo/Pericarditis 54% - Treatment discontinuation Neurological - "Hypothyroidism Meningoencephalitis SST - Demyelinating syndromes/NMJ disorders 12% LC 5% SLT NS 10% SST Non-significant Placebo/Follow up SST Significant short term Frequency of patient- 10% defined categories in Asymptomatic blood abnormalities NS Acute toxicity requiring steroids / Grade 1 AEs IMmotion010 placebo arm 75% hospital admission / treatment Infusion related reactions (n=274) discontinuation 6 Elizabeth Nally

[Slide 1] POTOMAC: 5-Year Overall Survival - ITT No detriment at the 5-year OS analysis was observed with the addition of durvalumab to BCG (I+M) therapy D+BCG (I+M) BCG (I+M) N=339 N=340 Deaths, n (%) 45 (13) 56 (16) Median OS NR NR 1.0 88% (95% CI), months (NR-NR) (NR-NR) 0.8 86% Probability of os 0.6 0.4 HR 0.81 (95% CI, 0.54-1.19) 0.2 Median follow-up: 72 months 0 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66 69 72 75 78 81 84 87 90 Time from randomization (months) No. of patients at risk D+BCG (I+M) 339 336 329 326 324 320 319 315 314 311 306 303 298 296 293 290 290 286 283 277 270 236 217 182 141 115 73 30 11 1 0 BCG (I+M) 340 338 336 333 330 328 326 322 317 313 313 313 309 305 301 295 292 288 284 281 275 239 220 185 140 108 70 32 12 0 0 in censored patients across treatment arms. Data cutoff 03 October 2025. OS is the time from randomization until death due to any cause regardless of whether the patient withdraws from randomized therapy or receives another anti cancer therapy. BCG, bacillus Calmette Guérin; CI, confidence interval; D. durvalumab; HR, hazard ratio; I, induction; ITT, intent to treat population; M, maintenance: NR, not reached; OS, ASCO overall survival #ASCO26 ASCO AMERICAN SOCIETY OF CLINICAL ONCOLOGY UAL MEETING Presentation is property of the author and ASCO Permission required for reuse, contact permissions@asco.org. KNOWLEDGE CONQUERS CANCER --- [Slide 2] POTOMAC PRO-CTCAE Symptoms PRO-CTCAE Symptom Worsening on Treatment Through Week 106 Abdominal pain 76% (39/51) D+BCG (I+M) (Interference) 68% (40/59) BCG (I+M) Across abdominal pain, diarrhea, and Abdominal pain 67% (162/241) painful urination, rates of PRO-CTCAE (Frequency) 63% (156/246) worsening were similar between treatment Abdomenal pain 59% (30/51) arms through Week 106, consistent with the (Seventy) 63% (37/59) shared BCG treatment backbone Diarrhea 60% (144/241) (Frequency) For urinary frequency, rates of PRO-CTCAE 65% (159/246) worsening were numerically higher with Painful unnation 83% (200/241) D+BCG (80%) VS BCG (73%), with a (Seventy) 82% (201/246) difference <10% Uninary frequency 79% (127/160) (Interference) 69% (125/181) Urinary frequency 80% (193/241) (Frequency) 73% (179/246) 0 20 40 60 80 100 Patients with any worsening (%)* Date cutcult 00 April 2025 Patents - remained PRO CTCAE soom during breatment/patents with baseficiar and if less 1 on bestment PRO-CTCAL - BCG, backs Calmette Code ASCO #ASCO26 D. L induction M, maintenance, PRO-CTCAL patient reported culcomer - of the Common Terminary Orderia for Adverse Events ASCO AMERICAN accept of - AL MEETING Presentation . property of the author and ASCO. Permission - lest - - any KNOWLEDGE CONQUERS CANCER --- [Slide 3] POTOMAC: EORTC QLQ-NMIBC24 Change From Baseline Adjusted mean change-from-baseline scores were not clinically meaningful and were similar between treatment arms Urinary Symptoms Intravesical Treatment Issues Difference between - for overall mean CFB: 1.2 (95% CL-1.19 to 3.65) Difference between ams for overal mean CFB:-1.2(85% CL-3.79 to 1.29) 20 20 10 12 1 I I mm Internal change I None 0 0 I Ester -10 I 50 -20 -29 . - Valt (weeks) Visit (weeks) ! ! - Future Perspective/Worries Sexual Functioning Difference behween - for overall mean CFB:-22 (95% CL, -5.11 to 0.00) Difference between anns for overall mean CFB: 1.1 (95% CL-1.30 to 3.45) 20 20 10 10 I I None I I H butter 0 0 Dellar Flose 10 -13 -20 -20 & I Vall (weeks) Vall (weeks) Clearally mesningful change from Landing Data culcul 03 April 25 Enter tars the 05% a Charge from Laneline was analyzed ving nued model for repeated I and helerogeneous Fooplitz with institution before, Instruction visit, buseless acces, treatment by - and baseline sours by - interactions as explaratory variables Only patients with an evaluable baselee - and at less - - are included b the analysis model A clinically meaninght change - defined - . 10-point change # address companed with baseline BCO. beciefus Committe-Outrin CFB, change - beseles, a confidence interval D, ASCO durvaluments EGRTC QLQ-NMIBC24 European Organisation by Research and Testment of Cancer Quality of Life Quantionnaire Non Invoice Baker Cancer 24 L induction M markssance ASCO INFECTS - #ASCO26 AL MEETING Presentation . possents of the who and ASCO - required for - - ENOWLEDGE COMQUERS --- [Slide 4] POTOMAC: EORTC QLQ-C30 Change From Baseline Adjusted mean changes from baseline showed modest deterioration in GHS/QoL and physical functioning and increased fatigue in both treatment arms, with generally similar changes between treatment arms GHS/QoL1 Physical Functioning Fatigue Difference between arms: -2.7 (95% CI, -4.85 to -0.54) Difference between arms: -2.6 (95% CI, -4.43 to -0.81) Difference between arms: 4.0 (95% CI, 1.50 to 6.46) 20 20 20 Adjusted mean change 10 from baseline Better Adjusted mean change 10 from baseline Better Worse Worse Adjusted mean change 10 0 from baseline Worse 0 0 10 -10 -10 Better -20 -20 -20 2 10 18 26 34 42 50 58 66 74 82 90 98 106114122130138146 2 10 18 26 34 42 50 58 66 74 82 90 98 106114122130138146 2 10 18 26 34 42 50 58 66 74 82 90 98 106114122130138146 Visit (weeks) Visit (weeks) Visit (weeks) No. of patients in analysis No of patients in analysis No. of patients in analysis D+BCG (1+11)214 189 180 177 174 171 156 149 142 148 138 138 130 126 122 117 104 105 D+BCG (1+M): 202 189 180 177 174 171 156 149 142 148 138 138 130 126 122 117 104 105 D+BCG (1+M) 202 189 180 177 174 171 156 149 142 148 138 138 130 126 122 117 104 105 BCG (1+M)232 219 213 192 193 178 183 158 165 165 158 149 152 138 139 133 120 124 123 BCG (I+M) 219 213 192 193 178 183 158 165 165 158 149 152 138 139 133 120 124 123 BCQ (1+M)232 219 213 192 193 178 183 158 165 165 158 149 152 138 139 133 120 124 123 Clinically meaningful change from baseline 1. De Santis M, of al. Lancet 2025,406,2221-2234 Data cutoff 03 April 2025. Decreases indicate worsening for GHS/QoL and physical functioning: increases indicate worsening for fatigue. Error bars show 95% CI. Change from baseline was analyzed using a mixed model for repeated measures and heterogenous Toeplitz, with stratification factors, treatment, visit, baseline score, treatment-by-visit and baseline score- by-visit interactions as explanatory variables. Only patients with an evaluable baseline score and at least 1 evaluable postbaseline score are included in the analysis model. A clinically meaningful change was defined as a 10-point change in score compared with baseline. BCG, bacillus Calmette-Guerin CFB, change from baseline; CI, confidence interval; D, durvalumab; EORTC QLQ-C30, European Organisation for ASCO Research and Treatment of Cancer 30-item core quality of life questionnaire; GHS/QoL. global health scale/quality of life; 1, induction, M, maintenance. ASCO AMERICAN SOCIETY OF #ASCO26 CUNICAL ONCOLOGY AL MEETING Presentation is property of the author and ASCO Permission required for reuse; contact permissions@asco.or KNOWLEDGE CONQUERS CANCER

[Slide 1] POTOMAC: 5-Year Overall Survival - ITT No detriment at the 5-year OS analysis was observed with the addition of durvalumab to BCG (I+M) therapy D+BCG (I+M) BCG (I+M) N=339 N=340 Deaths, (%) 45 (13) 56 (16) Median OS NR NR 1.0 88% (95% CI), months (NR-NR) (NR-NR) 0.8 86% Probability of OS 0.6 0.4 HR 0.81 (95% CI, 0.54-1.19) 0.2 Median follow-up: 72 months 0 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66 69 72 75 78 81 84 87 90 Time from randomization (months) No. of patients at risk D+BCG (I+M) 339 336 329 326 324 320 319 315 314 311 306 303 298 296 293 290 290 286 283 277 270 236 217 182 141 115 73 30 11 1 0 BCG (I+M) 340 338 336 333 330 328 326 322 317 313 313 313 309 305 301 295 292 288 284 281 275 239 220 185 140 108 70 32 12 0 0 % consored patients across treatment arms. Data outoff 03 October 2025 os 0 the time from randomization until death due to any cause regardless of whether the patient withdraws from randomized therapy or 26 ASCO #ASCO26 overall survival receives another and cancer therapy BCG, bacillus Calmette Gudrin CI, confidence interval; 0. durvalumab; HR, hazard ratio, induction; ITT. intent to treat population; M, maintenance NR, not reached 08, NUAL MEETING Presentation N property of the author and ASCO Permission required for - contact permissione@asco.org org. ASCO AMERICAN SOCE CUPICAL OHCOU KHOWLEDGE CONQUERS - CAN ASCO ASCO ASCO ASCO ASCO ASCO ASCO ASCO ASCO ASCO SCO ASCO ASCO ASCO ASCC ASCO D ASCO O ASCO ASC ASCO --- [Slide 2] POTOMAC: PRO Questionnaire Compliance and Baseline Scores Baseline questionnaire completion rate was high. Baseline PRO scores were similar between treatment arms and indicated high QoL and physical functioning and low symptom burden (e.g., fatigue) at study entry Absolute baseline PRO scoresᵇ Compliance D+BCG (I+M) BCG (I+M) EORTC QLQ-C30 D+BCG (I+M) №339 N=340 100 BCG (I+M) Mean score at baseline 80 High EORTC QLQ-C30 functioning 60 High GHS/Got Baseline assessment completed 74% 79% 40 Low 20 Baseline and 21 post-baseline symptom 72% 75% burden assessment completed 0 GHS/QoL Physical Fatigue Compliance rate range functioning 50%-82% 56%-84% (baseline - Week 138*) EORTC QLQ-NMIBC24 EORTC QLQ-NMIBC24 100 Baseline assessment completed 80% 82% Baseline and 21 post-baseline 78% Mean score at baseline 80 High 60 functioning 40 80% Low Low assessment completed 20 Low symptom symptom symptom burden burden burden Compliance rate range 0 50%-87% 56%-86% Urinary Intravesical treatment (baseline - Week 142°) Future perspective/ wornes Sexual functioning symptoms issues Data a 03 April 2025 Compliance range refects the lowest and highest - level compliance from bassine through Week 138 or Week 142 For GHS/QoL and functioning scales, higher scores indicate better Gol. and function For symptom ocales, higher scores indicate greater symptom burden, BCG bacillus Calmette Cubrin 0. durvalumab EORTC CI.Q-C30 European Organisation for Research and Treatment of Cancer form core quality of Me questionnaire, EORTC Q NMBC24 European Organisation for Research and Treatment of Cancer Quality of Questionnaire Non Muscle invoive Bladder 2026 ASCO #ASCO26 Cancer 24, GHS/QL poblic health acare/quality of the HRQX health-related quality of life, L induction M maintenance, PRO patient reported outcome, Onl, quality of the ASCO AMERICAN DURICAL - ANNUAL MEETING property of the author and ASCO Permission required for - contact permissions@ascs.org KHOWLEDGE CONQUERS CANCER ASCO ASCO ASCO ASCO ASCO A! ASCO ASCO ASCO ASCO ASCO ASCO ASCO ASCO ASCO ASCO A ASCO SCO ASCO SCO ASCO AS ASCO

FDA approves durvalumab for muscle invasive bladder cancer On March 28, 2025, the Food and Drug Administration approved durvalumab (Imfinzi, AstraZeneca) with gemcitabine and cisplatin as neoadjuvant treatment, followed by single agent durvalumab as adjuvant treatment following radical cystectomy, for adults with muscle invasive bladder cancer (MIBC). Full prescribing information for Imfinzi will be posted on Drugs@FDA. Efficacy and Safety Efficacy was evaluated in NIAGARA (NCT03732677), a randomized, open-label, multicenter, Phase III trial enrolling 1,063 patients who were candidates for radical cystectomy and had not received prior systemic therapy for bladder cancer. Patients were randomized (1:1) to receive neoadjuvant durvalumab with chemotherapy followed by adjuvant durvalumab after surgery or neoadjuvant chemotherapy followed by surgery alone. The major efficacy outcome was event-free survival (EFS) by blinded independent central review. Overall survival (OS) was an additional efficacy outcome. At a pre-specified interim analysis, the trial demonstrated a statistically significant improvement in EFS and OS. Median EFS was not reached (NR) (95% CI: NR, NR) in the durvalumab with chemotherapy arm and 46.1 months (95% CI: 32.2, NR) in the chemotherapy arm (hazard ratio 0.68 [95% CI: 0.56, 0.82]; two-sided p-value <0.0001). Median OS was not reached in either arm (hazard ratio 0.75 [95% CI: 0.59, 0.93]; two-sided p-value=0.0106). Adverse reactions were consistent with prior experience with durvalumab with platinum- based chemotherapy.

FDA approves a treatment for high-risk non-muscle invasive bladder cancer FDA

POTOMAC: Study Design A randomised, open-label, Phase 3, global study Durvalumab 1500 mg IV (Q4W X 13 cycles) Primary endpoint D+BCG (I+M) BCG Induction BCG Maintenance Study population N=339 DFS: D+BCG (I+M) vs BCG (I+M) 3 weekly doses at Age ≥18 years Weekly x 6 weeks 3ml 6m 12m 18m 24m NMIBC Key secondary endpoints BCG-naive High-risk tumour defined Durvalumab 1500 mg IV (Q4W X 13 cycles) DFS: D+BCG (I only) VS BCG (I+M) as any of the following: R D+BCG DFS at 24 months (1:1:1) T1 (I only) BCG Induction N=1018 CRR at 6 months N=339 High-grade/G3 Weekly X 6 weeksb CIS Other secondary endpoints Multiple and recurrent and large OS at 5 years (≥3 cm) BCG (I+M) N=340 BCG Induction BCG Maintenance Safety 3 weekly doses at EORTC QLQ-C30 Weekly x 6 weeks 3m 6m 12m 18m 24m Stratification factors: Higher risk papillary disease (yes VS no)a CIS (yes VS no) --- POTOMAC: Disease-Free Survival for D+BCG (I+M) vs BCG (I+M) - ITT POTOMAC met its primary endpoint with early and sustained DFS benefit D+BCG (I+M) BCG (I+M) N=339 N=340 Events, n (%) 67 (20) 98 (29) 1.0 92% Median DFS, months NR NR 87% (95% CI) (NR-NR) (74.0-NR) 82% 0.8 87% 82% 77% Probability of DFS 0.6 + 0.4 HR 0.68 (95% CI, 0.50-0.93) Stratified log-rank P value = 0.0154 0.2 Median follow-upb: 60.7 months 24% DFS maturity 0 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66 69 72 75 78 81 Time from randomisation (months) No of patients at risk D+BCG (I+M) 339 321 304 292 289 283 278 273 262 257 250 245 235 229 226 222 220 204 195 156 145 108 94 57 26 9 1 0 BCG (I+M) 340 322 303 292 283 276 271 265 258 254 249 244 237 235 231 227 225 209 196 160 150 101 86 50 20 8 0 0 --- POTOMAC: Disease-Free Survival for D+BCG (I Only) vs BCG (I+M) - ITT Difference in DFS between D+BCG (I only) vs BCG (I+M) arms was not statistically significant (key secondary endpoint) D+BCG (I only) BCG (I+M) N=339 N=340 Events, n (%) 105 (31) 98 (29) 1.0 Median DFS, months NR NR 87% (95% CI) (NR-NR) (74.0-NR) 82% 77% 0.8 86% 79% 74% Probability of DFS 0.6 0.4 HR 1.14 (95% CI, 0.86-1.50) Stratified log-rank P value = 0.3530 0.2 Median follow-upᵃ: 60.7 months 0 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66 69 72 75 78 81 Time from randomisation (months) No of patients at risk D+BCG (I only) 339 314 296 281 269 261 250 246 240 236 227 219 217 212 210 201 198 186 173 145 130 92 79 47 20 13 1 0 BCG (I+M) 340 322 303 292 283 276 271 265 258 254 249 244 237 235 231 227 225 209 196 160 150 101 86 50 20 8 0 0 --- POTOMAC: Conclusions Durvalumab in combination with BCG (I+M) resulted in a statistically significant and clinically meaningful improvement in DFS VS BCG (I+M) alone in patients with BCG-naïve, high-risk NMIBC Scan the QR code to access: at a median of 5 years of follow-up Slide presentation Plain language summary 32% reduction in risk of a DFS event (HR 0.68; 95% CI, 0.50-0.93; P=0.0154) Copies of this presentation obtained through the QR code are for personal Early and sustained DFS benefit with durvalumab (starting at <4 months) use only and may not be reproduced without written permission of the authors After a median follow-up of >5 years (14% maturity), a descriptive analysis showed an OS HR of 0.80 (95% CI, 0.53-1.20), demonstrating no detriment to OS with the addition of durvalumab Durvalumab plus BCG (I+M) had a tolerable and manageable safety profile that was consistent with the known safety profiles of the individual agents, with no deaths due to treatment-related AEs POTOMAC supports 1 year of durvalumab in combination with BCG induction and maintenance as a potential new treatment for patients with BCG-naïve, high-risk NMIBC congress BERLIN 2025 ESMO AE, adverse event BCG, bacillus Calmette-Guénn CI, confidence interval DFS, disease-free survival, HR hazard ratio; I, induction M, maintenance, NMIBC non-muscle-invasive bladder cancer, OS, overall survival

Q = AstraZeneca Imfinzi approved in the US in first and only immunotherapy combination for patients with BCG-naïve, high-risk non-muscle-invasive bladder cancer. PUBLISHED 28 May 2026

FDA Approves Durvalumab in Combination with Bacillus Calmette-Guerin for High-Risk Non- Muscle Invasive Bladder Cancer As a service to our members, the American Association for Cancer Research will distribute information from the U.S. Food and Drug Administration about newly approved novel therapies for cancer patients. By doing so, we aim to help the FDA inform cancer researchers and oncologists of recent approvals in a timely manner. Included in the email from the FDA will be a link to the product label, which will provide the relevant clinical information on the indication, contraindications, dosing, and safety. In sharing this information, the AACR does not endorse any product or therapy and does not take any position on the safety or efficacy of the product or therapy described. On May 28, 2026, the Food and Drug Administration approved durvalumab (Imfinzi, AstraZeneca) in combination with Bacillus Calmette-Guerin (BCG) for the treatment of adult patients with BCG-naïve, high-risk non-muscle invasive bladder cancer (NMIBC). Full prescribing information for Imfinzi will be posted on Drugs@FDA. Efficacy was evaluated in the POTOMAC study (NCT03528694), a randomized, open-label, multicenter trial that enrolled 1,018 patients with high-risk NMIBC following transurethral resection of bladder tumor. High- risl aving one of the f 7: T1 e tumor, carcinoma d (CIS), or multiple, recurrent, and large tumors. Patients

14:12 5G 010 thelancet.com X THE LANCET of Search for. Q COMMENT - Online first, October 17, 2025 Front-line durvalumab and BCG in the treatment of non-muscle- invasive bladder cancer Andrea Necchi a,b X . Alberto Briganti a,c . Francesco Montorsi a,c Affiliations & Notes < Article Info < Linked Articles (1) > Over the past 5 years, systemic therapy for urothelial carcinoma has changed considerably throughout the clinical stages. 1 In addition to regulatory approvals of immune-checkpoint inhibitor (ICI)-based therapies for muscle-invasive or metastatic disease, advances have also been made for non-muscle-invasive bladder cancer (NMIBC). Nadofaragene firadenovec-vncg, nogapendekin alfa inbakicept-pmln, and gemcitabine % Get Access Outline Share More

BERLIN 2025 ESMO congress BERLIN GERMANY 17-21 OCTOBER 2025 --- POTOMAC: Study Design A randomised, open-label, Phase 3, global study Durvalumab 1500 mg IV (Q4W X 13 cycles) D+BCG (I+M) Primary endpoint Study population N=339 BCG Induction BCG Maintenance 3 weekly doses at DFS: D+BCG (I+M) vs BCG (1+M) Age ≥18 years Weekly X 6 weeks® NMIBC 3m 6m 12m 1 Pm 24m BCG-naive Key secondary endpoints High-risk tumour defined R D+BCG Durvalumab 1500 mg IV (Q4W X 13 cycles) DFS: D+BCG 0 only) vs BCG (I+M) as any of the following: (1:11) (I only) DFS at 24 months T1 N=1018 BCG Induction High-grade/G3 N=339 CRR at 6 months Weekly X 6 weeks CIS Multiple and Other secondary endpoints recurrent and large OS at 5 years (>3 cm) BCG (I+M) BCG Induction BCG Maintenance N=340 Safety 3 weekly doses at Weekly X 6 weeks EORTC QLQ-C30 3m 5m 12m 18m 24m Stratification factors: Higher risk papillary disease (yes VS no)* CIS (yes VS no) All disease assessments were performed by the investigator. Defined 05 T1G3/T1 high-grade or multiple and recument and large tumours (those with I diameter of 23 and For patients with persistent OS Income I 3 months, a single BCG re-induction was administered weekly for 6 weeks according to local standard practice. ClinicalTrials gov, NCT03528694; EudraCT number, 2017-002979-26 BCG bacilus Calinete-Guém, Questionnaire: G, grade; , induction IV, intravenous, m, month; M maintenance; NMBC, non-muscle-invasive bladder cancer OS, overall survival, Q4W, every 4 weeks, R rendomisation CIS, carcinoma in situ, CRR complete response rate, D, durvalumab, DFS, disease-free survival, EORTC QLQ-C30, European Organisation for Research and Treatment of Cancer 30-tem Core Quality of Lie ESMO --- POTOMAC: Disease-Free Survival for D+BCG (I+M) VS BCG (I+M) - ITT POTOMAC met its primary endpoint with early and sustained DFS benefit D+BCG (I+M) BCG (I+M) N=339 N=340 1.0 Events, n (%) 92% 67(20) 98(29) Median DFS, months NR 87% NR (95% CI) 82% (NR-NR) (74.0-NR) 0.8 87% 82% 77% Probability of DFS 0.6 0.4 HR 0.68 (95% CI, 0.50-0.93) Stratified log-rank P value® = 0.0154 0.2 Median follow-upb: 60.7 months 24% DFS maturity 0 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66 69 72 75 78 81 Time from randomisation (months) No. of patients at risk D+BCG (I+M) 339 321 304 292 289 283 278 273 262 257 250 245 235 229 226 222 220 204 195 156 145 108 94 57 20 9 1 0 BCG (I+M) 340 322 303 292 283 276 271 265 258 254 249 244 237 235 231 227 225 209 196 160 150 101 86 50 20 8 0 0 DFS is defined as the time to the first: 1) recurrence of high-risk disease (recurrence of high-grade Ta, T1, or CIS, presentation with MIBC and/or metastatic disease or persistent CIS #6 months): 2) death by any cause in the absence of recurrence *The threshold to declare statistical significance was based on a generalized Haybittle-Peto spending function- with the observed number of events, the boundary for declaring statistical significance was 0.0317 for a 5% overall 2-sided alpha. Mn censored patients across all study arms. Data cutoff 03 April 2025 BCG, bacillus Calmette-Guénn; CL confidence interval, CIS, caronoma a sa, ESMO D, durvalumab; DFS, disease-free survival; HR, hazard ratio, I, induction; ITT, intent-to-treat population; M, maintenance, MIBC, muscle-invasive bladder cancer, NR not reached. --- POTOMAC: Conclusions Durvalumab in combination with BCG (I+M) resulted in a statistically significant and clinically meaningful improvement in DFS VS BCG (I+M) alone in patients with BCG-naive, high-risk NMIBC at a median of 5 years of follow-up Scan the OR code to access Side presentation 32% reduction in risk of a DFS event (HR 0.68; 95% CI, 0.50-0.93; P=0.0154) Plan language surmary Crass If is - and trugh to DI - is " - Early and sustained DFS benefit with durvalumab (starting at <4 months) - (6) as ray - etc. - # for ukin After a median follow-up of >5 years (14% maturity), a descriptive analysis showed an OS HR of 0.80 (95% CI, 0.53-1.20), demonstrating no detriment to OS with the addition of durvalumab Durvalumab plus BCG (I+M) had a tolerable and manageable safety profile that was consistent with the known safety profiles of the individual agents, with no deaths due to treatment-related AEs POTOMAC supports 1 year of durvalumab in combination with BCG induction and maintenance as a potential new treatment for patients with BCG-naïve, high-risk NMIBC an AE, adverse event, BCG, bacillus Calmette-Guérin CI, confidence interval; DFS, disease free survival, HR, hazard ratio, 1, induction M. mantenance, NMBC, non made name Madder canar, 05, overall und ESMO

M R Mill IIICR Maria De Santis Chair, Interdisciplinary Uro-Oncology Section, Charité Universitätsmedizin, Berlin, Germany

POTOMAC: Study Design A randomised, open-label, Phase 3, global study Durvalumab 1500 mg IV (Q4W X 13 cycles) Primary endpoint D+BCG (I+M) BCG Induction BCG Maintenance Study population N=339 DFS: D+BCG (I+M) vs BCG (I+M) 3 weekly doses at Age ≥18 years Weekly x 6 weeks 3ml 6m 12m 18m 24m NMIBC Key secondary endpoints BCG-naive High-risk tumour defined Durvalumab 1500 mg IV (Q4W X 13 cycles) DFS: D+BCG (I only) VS BCG (I+M) as any of the following: R D+BCG DFS at 24 months (1:1:1) T1 (I only) BCG Induction N=1018 CRR at 6 months N=339 High-grade/G3 Weekly X 6 weeksb CIS Other secondary endpoints Multiple and recurrent and large OS at 5 years (≥3 cm) BCG (I+M) N=340 BCG Induction BCG Maintenance Safety 3 weekly doses at EORTC QLQ-C30 Weekly x 6 weeks 3m 6m 12m 18m 24m Stratification factors: Higher risk papillary disease (yes VS no)a CIS (yes VS no) --- POTOMAC: Disease-Free Survival for D+BCG (I+M) VS BCG (I+M) - ITT POTOMAC met its primary endpoint with early and sustained DFS benefit D+BCG (I+M) BCG (I+M) N=339 N=340 Events, n (%) 67 (20) 98 (29) 1.0 92% Median DFS, months NR NR 87% (95% CI) (NR-NR) (74.0-NR) 82% 0.8 87% 82% 77% Probability of DFS 0.6 + 0.4 HR 0.68 (95% CI, 0.50-0.93) Stratified log-rank P valueᵃ = 0.0154 0.2 Median follow-upb: 60.7 months 24% DFS maturity 0 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66 69 72 75 78 81 Time from randomisation (months) No of patients at risk D+BCG (I+M) 339 321 304 292 289 283 278 273 262 257 250 245 235 229 226 222 220 204 195 156 145 108 94 57 26 9 1 0 BCG (I+M) 340 322 303 292 283 276 271 265 258 254 249 244 237 235 231 227 225 209 196 160 150 101 86 50 20 8 0 0 --- POTOMAC: Disease-Free Survival for D+BCG (I Only) vs BCG (I+M) - ITT Difference in DFS between D+BCG (I only) vs BCG (I+M) arms was not statistically significant (key secondary endpoint) D+BCG (I only) BCG (I+M) N=339 N=340 Events, n (%) 105 (31) 98 (29) 1.0 Median DFS, months NR NR 87% (95% CI) (NR-NR) (74.0-NR) 82% 77% 0.8 86% 79% 74% Probability of DFS 0.6 0.4 HR 1.14 (95% CI, 0.86-1.50) Stratified log-rank P value = 0.3530 0.2 Median follow-upᵃ: 60.7 months 0 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66 69 72 75 78 81 Time from randomisation (months) No of patients at risk D+BCG (I only) 339 314 296 281 269 261 250 246 240 236 227 219 217 212 210 201 198 186 173 145 130 92 79 47 20 13 1 0 BCG (I+M) 340 322 303 292 283 276 271 265 258 254 249 244 237 235 231 227 225 209 196 160 150 101 86 50 20 8 0 0 --- POTOMAC: Conclusions Durvalumab in combination with BCG (I+M) resulted in a statistically significant and clinically meaningful improvement in DFS VS BCG (I+M) alone in patients with BCG-naïve, high-risk NMIBC Scan the QR code to access: at a median of 5 years of follow-up Slide presentation Plain language summary 32% reduction in risk of a DFS event (HR 0.68; 95% CI, 0.50-0.93; P=0.0154) Copies of this presentation obtained through the QR code are for personal Early and sustained DFS benefit with durvalumab (starting at <4 months) use only and may not be reproduced without written permission of the authors After a median follow-up of >5 years (14% maturity), a descriptive analysis showed an OS HR of 0.80 (95% CI, 0.53-1.20), demonstrating no detriment to OS with the addition of durvalumab Durvalumab plus BCG (I+M) had a tolerable and manageable safety profile that was consistent with the known safety profiles of the individual agents, with no deaths due to treatment-related AEs POTOMAC supports 1 year of durvalumab in combination with BCG induction and maintenance as a potential new treatment for patients with BCG-naïve, high-risk NMIBC congress BERLIN 2025 ESMO AE, adverse event BCG, bacillus Calmette-Guénn CI, confidence interval, DFS, disease-free survival HR hazard ratio, I, induction M. maintenance, NMIBC non-muscle-invasive bladder cancer, OS, overall survival

POTOMAC: Study Design A randomised, open-label, Phase 3, global study Durvalumab 1500 mg IV (Q4W x 13 cycles) Primary endpoint D+BCG (I+M) BCG Induction BCG Maintenance Study population N=339 DFS: D+BCG (I+M) vs BCG (I+M) 3 weekly doses at Age ≥18 years Weekly x 6 weeks 3ml. 6m 12m 18m 24m NMIBC Key secondary endpoints BCG-naive High-risk tumour defined Durvalumab 1500 mg IV (Q4W X 13 cycles) DFS: D+BCG (I only) VS BCG (I+M) as any of the following: R D+BCG DFS at 24 months (1:1:1) T1 (I only) BCG Induction N=1018 CRR at 6 months N=339 High-grade/G3 Weekly X 6 weeksb CIS Other secondary endpoints Multiple and recurrent and large OS at 5 years (≥3 cm) BCG (I+M) N=340 BCG Induction BCG Maintenance Safety 3 weekly doses at EORTC QLQ-C30 Weekly x 6 weeks 3m 6m 12m 18m 24m Stratification factors: Higher risk papillary disease (yes VS no)a CIS (yes VS no) --- POTOMAC: Disease-Free Survival for D+BCG (I+M) VS BCG (I+M) - ITT POTOMAC met its primary endpoint with early and sustained DFS benefit D+BCG (I+M) BCG (I+M) N=339 N=340 Events, n (%) 67 (20) 98 (29) 1.0 92% Median DFS, months NR NR 87% (95% CI) (NR-NR) (74.0-NR) 82% 0.8 87% 82% 77% Probability of DFS 0.6 + 0.4 HR 0.68 (95% CI, 0.50-0.93) Stratified log-rank P valueᵃ = 0.0154 0.2 Median follow-upb: 60.7 months 24% DFS maturity 0 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66 69 72 75 78 81 Time from randomisation (months) No of patients at risk D+BCG (I+M) 339 321 304 292 289 283 278 273 262 257 250 245 235 229 226 222 220 204 195 156 145 108 94 57 26 9 1 0 BCG (I+M) 340 322 303 292 283 276 271 265 258 254 249 244 237 235 231 227 225 209 196 160 150 101 86 50 20 8 0 0 --- POTOMAC: Disease-Free Survival for D+BCG (I Only) vs BCG (I+M) - ITT Difference in DFS between D+BCG (I only) vs BCG (I+M) arms was not statistically significant (key secondary endpoint) D+BCG (I only) BCG (I+M) N=339 N=340 Events, n (%) 105 (31) 98 (29) 1.0 Median DFS, months NR NR 87% (95% CI) (NR-NR) (74.0-NR) 82% 77% 0.8 86% 79% 74% Probability of DFS 0.6 0.4 HR 1.14 (95% CI, 0.86-1.50) Stratified log-rank P value = 0.3530 0.2 Median follow-upᵃ: 60.7 months 0 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66 69 72 75 78 81 Time from randomisation (months) No of patients at risk D+BCG (I only) 339 314 296 281 269 261 250 246 240 236 227 219 217 212 210 201 198 186 173 145 130 92 79 47 20 13 1 0 BCG (I+M) 340 322 303 292 283 276 271 265 258 254 249 244 237 235 231 227 225 209 196 160 150 101 86 50 20 8 0 0 --- POTOMAC: Conclusions Durvalumab in combination with BCG (I+M) resulted in a statistically significant and clinically meaningful improvement in DFS VS BCG (I+M) alone in patients with BCG-naïve, high-risk NMIBC Scan the QR code to access: at a median of 5 years of follow-up Slide presentation Plain language summary 32% reduction in risk of a DFS event (HR 0.68; 95% CI, 0.50-0.93; P=0.0154) Copies of this presentation obtained through the QR code are for personal Early and sustained DFS benefit with durvalumab (starting at <4 months) use only and may not be reproduced without written permission of the authors After a median follow-up of >5 years (14% maturity), a descriptive analysis showed an OS HR of 0.80 (95% CI, 0.53-1.20), demonstrating no detriment to OS with the addition of durvalumab Durvalumab plus BCG (I+M) had a tolerable and manageable safety profile that was consistent with the known safety profiles of the individual agents, with no deaths due to treatment-related AEs POTOMAC supports 1 year of durvalumab in combination with BCG induction and maintenance as a potential new treatment for patients with BCG-naïve, high-risk NMIBC congress BERLIN 2025 ESMO AE, adverse event BCG, bacillus Calmette-Guénn CI, confidence interval, DFS, disease-free survival HR hazard ratio, I, induction M. maintenance NMIBC non-muscle-invasive bladder cancer, OS, overall survival

Durvalumab in combination with BCG for BCG-naive, high- risk, non-muscle-invasive bladder cancer (POTOMAC): final analysis of a randomised, open-label, phase 3 trial Maria De Santis, Joan Palou Redorta, Hiroyuki Nishiyama, Michal Krawczyński, Artur Seyitkuliev, Andrey Novikov, Félix Guerrero-Ramos, Ruslan Zukov, Minoru Kato, Takashi Kawahara, Lieven Goeman, Javier Puente, Eva Hellmis, Thomas Powles, Piotr Radziszewski, Kilian M Gust, Paul Vasey, Pierre Bigot, Yves Fradet, Jarmo Hunting, Jon Armstrong, Suliman Boulos, Stephan Hois, Neal D Shore, on behalf of the POTOMAC Investigators* Summary Background Patients with high-risk non-muscle-invasive bladder cancer (NMIBC) often have recurrence or progression after transurethral resection of bladder tumour (TURBT) and subsequent BCG therapy. We aimed to evaluate whether 1 year of durvalumab with BCG could improve outcomes versus BCG alone for these patients. Methods This randomised, open-label, phase 3 trial enrolled patients aged 18 years or older with BCG-naive, high-risk NMIBC who underwent TURBT. Patients were randomly allocated (1:1:1) to receive intravenous durvalumab (every 4 weeks for 13 cycles) plus intravesical BCG induction (weekly for 6 weeks) and maintenance (three doses at weekly intervals at 3, 6, 12, 18, and 24 months), durvalumab plus BCG induction, or BCG induction and maintenance (comparison group). The primary endpoint was investigator-assessed disease-free survival in the durvalumab plus BCG induction and maintenance group versus the comparison group in the intention-to-treat population. This study is registered at ClinicalTrials.gov (NCT03528694) and EudraCT (2017-002979-26) and is ongoing but is no longer enrolling patients. Findings Between June 18, 2018, and Oct 2, 2020, 1350 patients were assessed for eligibility, among whom 1018 patients were randomly allocated: 339 to the durvalumab plus BCG induction and maintenance group (of whom 336 [99%] initiated and 180 [53%] completed treatment), 339 to the durvalumab plus BCG induction group (337 [99%] initiated and 239 [71%] completed treatment), and 340 to the comparison group (339 [>99%] initiated and 182 [54%] completed treatment). At a median follow-up of 60.7 months (IQR 51.5-66.5), there were 67 (20%) disease- free survival events in the durvalumab plus BCG induction and maintenance group and 98 (29%) events in the comparison group, resulting in a 32% reduction in the risk of recurrence of high-risk disease or death by any cause with durvalumab plus BCG induction and maintenance versus the comparison group (hazard ratio 0.68 [95% CI .50-0.93]; log-rank p=0.015). Among patients who received at least one dose of study treatment, grade 3 or 4 treatment-related adverse events occurred in 71 (21%) of 336 patients in the durvalumab plus BCG induction and maintenance group, 52 (15%) in the durvalumab plus BCG induction only group, and 13 (4%) of 339 patients in the comparison group. No treatment-related adverse events led to death. Interpretation Among patients with BCG-naive, high-risk NMIBC, 1 year of durvalumab combined with BCG induction and maintenance therapy showed a statistically significant and clinically meaningful improvement in disease-free survival versus BCG induction and maintenance alone. The combination had a manageable safety profile, consistent with that of the individual therapies. These results support 1 year of durvalumab in combination with BCG induction and maintenance therapy as a potential new treatment for this patient population. Funding AstraZeneca. --- 1350 patients assessed for eligibility 332 excluded 314 not eligible 15 withdrew consent 3 other reasons 1018 randomly assigned 339 assigned to durvalumab plus BCG 339 assigned to durvalumab plus BCG 340 assigned to BCG induction and induction and maintenance (included induction (included in intention-to- maintenance alone (comparison in intention-to-treat analysis) treat analysis) group; included in intention-to-treat analysis) 3 untreated 2 untreated 1 untreated 2 withdrew consent 1 withdrew consent 1 withdrew consent 1 missing reason 1 other reason 336 received at least one dose of study 337 received at least one dose of study 339 received at least one dose of study treatment (included in safety analysis) treatment (included in safety analysis) treatment (included in safety analysis) 180 completed treatment 239 completed treatment 182 completed treatment 156 discontinued treatment 98 discontinued treatment 157 discontinued treatment 61 adverse event 38 adverse event 74 adverse event 45 patient decision 13 patient decision 22 patient decision 31 met discontinuation criteria 37 met discontinuation criteria 52 met discontinuation criteria 2 due to COVID-19 pandemic 8 due to COVID-19 pandemic 1 due to COVID-19 pandemic 1 lost to follow-up 2 other reasons 8 other reasons 16 other reasons 0 still on treatment at data cutoff 0 still on treatment at data cutoff 0 still on treatment at data cutoff 270 still in study at data cutoff* 272 still in study at data cutoff* 263 still in study at data cutoff* --- Durvalumab plus Durvalumab plus Comparison BCG induction and BCG induction group group maintenance group (n=339) (n=340) (n=339) Age, years Median (IQR) 68 (61-74) 68 (61-73) 67 (61-73) <65 121 (36%) 123 (36%) 137 (40%) >65 218 (64%) 216 (64%) 203 (60%) Sex Male 276 (81%) 272 (80%) 271 (80%) Female 63 (19%) 67 (20%) 69 (20%) Race White 267 (79%) 267 (79%) 268 (79%) Asian 61 (18%) 63 (19%) 60 (18%) Other 4 (1%) 6 (2%) 8 (2%) Missing 7 (2%) 3 (1%) 4 (1%) Ethnicity Hispanic or Latino 17 (5%) 14 (4%) 10 (3%) Not Hispanic or Latino 322 (95%) 325 (96%) 330 (97%) Region Western Europe 143 (42%) 126 (37%) 135 (40%) Rest of world 196 (58%) 213 (63%) 205 (60%) ECOG performance status score 0 294 (87%) 305 (90%) 304 (89%) 1 45 (13%) 34 (10%) 36 (11%) Smoking status Current 62 (18%) 60 (18%) 63 (19%) Former 175 (52%) 182 (54%) 173 (51%) Never 102 (30%) 97 (29%) 104 (31%) Carcinoma in situ* Yes 125 (37%) 125 (37%) 125 (37%) No 214 (63%) 214 (63%) 215 (63%) Papillary disease only Yes 217 (64%) 222 (65%) 220 (65%) No 122 (36%) 117 (35%) 120 (35%) T1 diseaset 195 (58%) 191 (56%) 211 (62%) Ta diseaset 112 (33%) 114 (34%) 99 (29%) Tumour PD-L1 expression High$ 81 (24%) 90 (27%) 85 (25%) Low or negative 235 (69%) 228 (67%) 232 (68%) Missing or non-evaluable 23 (7%) 21 (6%) 23 (7%) Data are median (IQR) or n (%). ECOG=Eastern Cooperative Oncology Group. *Per interactive voice response system; data represent patients who had carcinoma in situ (with or without papillary disease) at baseline. +Data represent patients who had papillary disease (with or without carcinoma in situ). #PD-L1 status was determined by the percentage of tumour cells with any membrane staining above background or by the percentage of tumour-associated immune cells with staining at any intensity above background; ICP represents the percentage of tumour area occupied by any tumour-associated immune cells; IC+ represents the percentage area of ICP showing PD-L1 positive immune cell staining. SPD-L1 status was considered high if any of the following criteria were met: >25% of tumour cells showed membrane staining; or ICPwas 1% and IC+ was >25%; or ICP was 1% and IC+ was 100%. Table 1: Baseline demographic and disease characteristics of patients in the intention-to-treat population --- A 100 91.7% Durvalumab plus BCG (I+M) group 86-5% Comparison group 81-8% HR 0-68 (95% CI 0-50-0-93); p=0-015 80 86.8% 81-6% 77-4% Disease-free survival (%) 60 40 20 0 0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66 69 72 75 78 81 Number at risk Time from randomisation (months) (censored) Durvalumab plus BCG (I+M) group 339 321 304 292 289 283 278 273 262 257 250 245 235 229 226 222 220 204 195 156 145 108 94 57 26 9 1 0 (0) (11) (18) (22) (23) (24) (25) (27) (34) (35) (38) (41) (47) (50) (53) (57) (58) (72) (79) (117) (128) (165) (179) (216) (246) (263) (271) (271) Comparison group 340 322 303 292 283 276 271 265 258 254 249 244 237 235 231 227 225 209 196 160 150 101 86 50 20 8 0 0 (0) (4) (8) (9) (13) (13) (15) (19) (21) (22) (24) (27) (29) (30) (32) (34) (34) (49) (59) (93) (100) (147) (161) (194) (223) (234) (241) (241) B Disease-free survival events, n/N (%) HR (95% CI) Durvalumab plus BCG (I+M) group Comparison group All patients 67/339 (20%) 98/340 (29%) 0.68 (0-50-0-93) Age at randomisation, years <65 21/121 (17%) 32/137 (23%) 0.74 (0-42-1-27) >65 46/218 (21%) 66/203 (33%) 0.64 (0-44-0-93) Sex Male 50/276 (18%) 82/271 (30%) 0.59 (0-41-0-83) Female 17/63 (27%) 16/69 (23%) 1-21 (0-61-2-42) Region Western Europe 27/143 (19%) 40/135 (30%) 0.59 (0-36-0-95) Rest of world 40/196 (20%) 58/205 (28%) 0.75 (0-50-1-12) ECOG Performance Status 0 51/294 (17%) 82/304 (27%) 0-64 (0-45-0-90) 1 16/45 (36%) 16/36 (44%) 0.77 (0-38-1-56) Smoking status Current 9/62 (15%) 22/63 (35%) 0.38 (0-17-0-80) Former 38/175 (22%) 48/173 (28%) 0.80 (0-52-1-22) Never 20/102 (20%) 28/104 (27%) 0.74 (0-41-1-31) BCG strain TICE 20/87 (23%) 23/75 (31%) 0-68 (0-37-1-23) Other 46/249 (18%) 75/264 (28%) 0-66 (0-46-0-95) Carcinoma in situ* Yes 32/125 (26%) 33/125 (26%) 1-01 (0-62-1-64) No 35/214 (16%) 65/215 (30%) 0.53 (0-34-0-79) Higher-risk papillary diseaset Yes 32/173 (18%) 57/173 (33%) 0.54 (0-35-0-83) No 35/166 (21%) 41/167 (25%) 0.88 (0-56-1-38) PD-L1 status: HighS 15/81 (19%) 30/85 (35%) 0.50 (0-26-0-91) Low or negative 44/235 (19%) 61/232 (26%) 0.72 (0-48-1-05) Missing or non-evaluable 8/23 (35%) 7/23 (30%) NC (NC-NC) 0-10 0-25 0-50 1-00 1.50 2.50 Favours durvalumab plus BCG (I+M) Favours BCG (I+M)