#1AstraZeneca B Investor science conference call: American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium 2022 Conference call for investors and analysts 23 February 2022#2Forward-looking statements In order, among other things, to utilise the 'safe harbour' provisions of the US Private Securities Litigation Reform Act of 1995, AstraZeneca (hereafter 'the Group') provides the following cautionary statement: this document contains certain forward-looking statements with respect to the operations, performance and financial condition of the Group, including, among other things, statements about expected revenues, margins, earnings per share or other financial or other measures. 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Nothing in this document, or any related presentation/webcast, should be construed as a profit forecast. 2 B#33 Speakers Dr Fred Saad Principal Investigator PROpel, Professor and Chief of Urology, University of Montreal Hospital Centre, Canada Dave Fredrickson Executive Vice President, Oncology Business Unit Andy Barnett Global Franchise Head, GU and GYN Cancers, DDR and Established Oncology (for Q&A) CHAP Susan Galbraith Executive Vice President, Oncology R&D Sunil Verma Senior Vice President, Global Head of Oncology, Medical (for Q&A) B#4Agenda 4 1 2 3 4 5 Introduction: AstraZeneca @ ASCO GU 2022 Lynparza Phase III PROpel trial Opportunity and unmet need in mCRPC Other ASCO GU highlights Closing and Q&A#51 Introduction Susan Galbraith Executive Vice President, Oncology R&D#66 Comprehensive portfolio to combat cancer ENHERTUⓇ fam-trastuzumab deruxtecan-nxki 20 mg/mL INJECTION FOR INTRAVENOUS USE SIMFINZIⓇ durvalumab Injection for Intravenous Use 50 mg/mL Source: AstraZeneca. Lynparza™ olaparib TAGRISSOⓇ osimertinib CALQUENCE (acalabrutinib) 100 mg capsules Redirect local immunity Awaken dormant immune cells Targeted delivery of medicines that recruit immunity Build synthetic immunity Cell therapy Infuse with engineered T cells Build on PDx Overcome immune suppression Diverse pipeline with potential for orthogonal combinations Oncolytic virus Immune engagers Activate immune system Microenvironment Immuno-oncology "Ignore axis" "Defend axis" Tumour drivers and resistance Direct killing Tumour DNA damage response Oncogenic truncal drivers and mechanisms of resistance Synthetic lethality exploiting impaired DNA damage response Antibody drug conjugates Radioimmuno- conjugates Nanomedicines Replacing standard of care (i.e., chemo) with targeted delivery of toxic molecules Epigenetics Reprogramming tumour cells B#7ASCO GU 2022 ASCO Genitourinary Cancers Symposium 7 ● 19 abstracts with three oral presentations Two Oral presentations One Mini-oral presentation 16 Posters 19 Abstracts accepted ● ● Data highlights Lynparza + abiraterone in 1st-line mCRPC PROpel Phase III trial Lynparza + Imfinzi in 1st-line urothelial carcinoma BAYOU Phase II trial Enhertu + nivolumab in HER2+ urothelial carcinoma U105 Phase lb trial Source: ASCO GU 2022 accepted abstracts. Inclusive of externally sponsored research and partner-led trials. mCRPC = metastatic castration resistant prostate cancer; HER2+ = human epidermal receptor 2 positive. B#8Lynparza and abiraterone Success in Study 08 paved the way for PROpel in 1st-line mCRPC Radiographic progression-free survival (%) 100- 80- 60- 40- 20- Number at risk (number censored) Olaparib and abiraterone 71 (0) Placebo and abiraterone 71 (0) Study 08¹ Phase II trial T6 9 58 (5) 50 (6) 42 (8) 48 (3) 39 (4) 25 (5) 12 15 - Olaparib and abiraterone (n=71) -Placebo and abiraterone (n=71) HR 0-65 (95% CI 0-44-0-97); p=0-034 18 21 24 33 (9) 26 (12) 21 (13) 18 (13) 13 (17) 8 (19) 0 (25) 21 (7) 19 (7) 16 (7) 14 (7) 10 (8) 7 (10) 0 (17) 35% risk reduction Significant rPFS benefit regardless of HRRm status PARP-signaling and AR-signaling pathway interaction may explain combined effect Lynparza + abiraterone²-4 PARP involved in androgen- receptor-dependent transcription; PARP inhibition may increase activity of NHAs² NHA-induced HRR deficiency increasing susceptibility to PARP inhibition 3,4 Combined effect Antitumour activity in HRRm and non- HRRm prostate cancer²-4 8 1. Saad et al Lancet Oncol 2018; 19: 975-86 2. Schiewer MJ, et al. Cancer Discov. 2012;2:1134-1149 3. Polkinghorn WR, et al. Cancer Discov. 2013;3:1245-12534. Asim M, et al. Nat Commun. 2017;8(1):374. rPFS = radiographic progression free survival; HRR = homologous recombination repair; HRRm = HRR gene mutation; PARP = poly adenosine diphosphate-ribose polymerase; AR = androgen receptor; NHA = new hormonal agents.#92 Lynparza PROpel Dr Fred Saad Principal Investigator, PROpel Phase III trial#10PROpel A global randomised double-blind Phase III trial Patient population • 1L mCRPC ● ● ● ● Docetaxel allowed at mHSPC stage ● No prior abiraterone Other NHAs allowed if stopped >12 months prior to enrollment Ongoing ADT ECOG 0-1 Stratification factors Site of distant metastases: bone only vs visceral vs other • Prior taxane at mHSPC: yes vs no - 1:1 Olaparib 300 mg bid + abiraterone 1000 mg qd* n=399 Full dose of olaparib and abiraterone used Placebo + abiraterone 1000 mg qd* n=397 Full dose of abiraterone used Primary endpoint Radiographic progression or death (rPFS) by investigator assessment 10 *In combination with prednisone or prednisolone 5 mg bid. +HRRm, homologous recombination repair mutation, including 14 genes panel. ADT androgen deprivation therapy; bid = twice daily; ECOG = Eastern Cooperative Oncology Group; mHSPC = metastatic hormone sensitive prostate cancer. ● Key secondary endpoint Overall survival (alpha control) Additional endpoints Time to first subsequent therapy or death (TFST) Time to second progression or death (PFS2) Objective response rate (ORR) HRRm¹ prevalence (retrospective testing) Health-related quality of life Safety and tolerability ● ● ● First patient randomized: Nov 2018; Last patient randomized: Mar 2020; DCO1: July 30, 2021, for interim analysis of rPFS and OS. Multiple testing procedure is used in this study: 1-sided alpha of 0.025 fully allocated to rPFS. If the rPFS result is statistically significant, OS to be tested in a hierarchical fashion with alpha passed on to OS. +Please access the Supplement at https://bit.ly/3r50ms0 for more details. B#11Baseline patient characteristics Well-balanced between treatment arms Median (range) age, years ECOG performance status, n (%) 0 1 Symptomatic,* n (%) Site of metastases, n (%) Bone Distant lymph nodes Locoregional lymph nodes Lung Liver Docetaxel treatment at mHSPC stage, n (%) Median PSA, ug/L (IQR) HRRm status* HRRm Non-HRRm HRRm unknown Olaparib + abiraterone (n=399) 69.0 (43-91) 286 (71.7) 112 (28.1) 103 (25.8) 349 (87.5) 133 (33.3) 82 (20.6) 40 (10.0) 15 (3.8) 90 (22.6) 17.90 (6.09-67.00) 111 (27.8) 279 (69.9) 9 (2.3) Placebo + abiraterone (n=397) 70.0 (46-88) 272 (68.5) 124 (31.2) 80 (20.2) 339 (85.4) 119 (30.0) 89 (22.4) 42 (10.6) 18 (4.5) 89 (22.4) 16.81 (6.26-53.30) 115 (29.0) 273 (68.8) 9 (2.3) *Patients with symptomatic pain at baseline: BPI-SF item #3 score 24 and/or opiate use at baseline. +The HRRm status of patients in PROpel was determined retrospectively using results from tumor tissue and plasma ctDNA HRRm tests. Patients were classified as HRRm if (one or more) HRR gene mutation was detected by either test; patients were classified as non-HRRm if no HRR gene mutation was detected by either test; patients were classified as unknown HRRm if no valid HRR test result from either test was achieved. Please access the Supplement via 11 the QR code at the end of this presentation for more details. BPI-SF = Brief Pain Inventory - Short Form; ctDNA = circulating tumor DNA; IQR = interquartile range; PSA = prostate-specific antigen. 3#12Primary endpoint: rPFS by investigator-assessment 34% risk reduction of progression or death with olaparib + abiraterone Probability of rPFS 1.0 0.9 0.8- 0.7 0.6 0.5 0.4 0.3 - 0.2 0.1 0.0 No. at risk Olaparib + abiraterone Placebo + abiraterone T 0 T 10 12 14 16 18 20 Time from randomization (months) 399 395 367 354 340 337 313 309 301 277 274 265 251 244 277 221 219 170 167 163 104 100 87 59 57 28 26 25 5 397 393 359 356 338 334 306 303 297 266 264 249 232 228 198 190 186 143 141 137 87 84 73 45 43 21 17 16 2 N 1 4 6 T 8 Events: 394; Maturity 49.5% 12 *In combination with prednisone or prednisolone CI= confidence interval; HR = hazard ratio. 12-month rate 71.8% 63.4% T 24-month rate 51.4% 33.6% 22 24 1 26 28 4 2 30 4 1 ос Events, n (%) Median rPFS (months) HR (95% CI) Olaparib + abiraterone (n=399) 168 (42.1) 24.8 Placebo + abiraterone (n=397) 226 (56.9) 16.6 0.66 (0.54-0.81); P<0.0001 Pre-specified 2-sided alpha: 0.0324 Median rPFS improvement of 8.2 months favors olaparib + abiraterone* B#13Secondary endpoint: rPFS by blinded independent central review* 39% risk reduction of progression or death, highly consistent with the primary analysis Probability of rPFS 13 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 No. at risk Olaparib + abiraterone Placebo + abiraterone 0 2 4 10 12 14 16 18 20 Time from randomization (months) 399 389 353 347 332 331 314 309 303 283 275 267 249 240 221 217 215 165 161 159 96 89 80 55 53 30 28 26 5 397 388 345 340 322 319 294 289 282 251 245 226 209 204 177 172 168 131 126 124 73 70 62 39 38 21 16 15 2 6 12-month rate 73.8% 60.6% 8 24-month rate 53.7% 34.1% *Predefined sensitivity analysis. +Nominal. In combination with prednisone or prednisolone. 900 6 of 22 24 26 28 4 2 30 4 1 o o 0 0 Events, n (%) Median rPFS (months) HR (95% CI) Olaparib + abiraterone (n=399) 157 (39.3) 27.6 Placebo + abiraterone (n=397) 218 (54.9) 16.4 0.61 (0.49-0.74) P<0.0001¹ Median rPFS improvement of 11.2 months favors olaparib + abiraterone* B#14Subgroup analysis of rPFS rPFS benefit observed across all pre-specified subgroups All patients Age at randomization <65 265 ECOG performance status at baseline 1 Site of distant metastases Bone only Visceral Other Docetaxel treatment at mHSPC stage Yes No Baseline PSA Below median baseline PSA Above or equal to median baseline PSA HRRm status* HRRm Non-HRRm Number of patients, n 796 227 569 558 236 434 105 257 189 607 396 397 226 570 Median rPFS, months 24.8 NR 22.0 24.9 17.5 27.6 13.7 20.5 27.6 24.8 25.2 18.5 NR 24.1 16.6 16.4 16.7 16.8 14.6 22.2 10.9 13.7 13.8 16.8 22.0 13.8 13.9 19.0 0.1 Olaparib + abiraterone better 1 HR (95% CI) 0.66 (0.54-0.81) 0.51 (0.35-0.75) 0.78 (0.62-0.98) 0.67 (0.52-0.85) 0.75 (0.53-1.06) 0.73 (0.54-0.98) 0.62 (0.39-0.99) 0.62 (0.44-0.85) 0.61 (0.40-0.92) 0.71 (0.56-0.89) 0.75 (0.55-1.02) 0.63 (0.48-0.82) 0.50 (0.34-0.73) 0.76 (0.60-0.97) 10 Placebo + abiraterone better Global interaction test not significant at 10% level. *The HRRm status of patients in PROpel was determined retrospectively using results from tumor tissue and plasma ctDNA HRRm tests. Patients were classified as HRRm if (one or more) HRR gene mutation was detected by either test; patients were classified as non-HRRm patients if no HRR gene mutation was detected by either test; patients were classified as unknown HRRm if no valid HRR test result from 14 either test was achieved. 18 patients did not have a valid HRR testing result from either a tumor tissue or ctDNA test and were excluded from the subgroup analysis. This subgroup analysis is post hoc exploratory analysis. Please access the Supplement via the QR code at the end of this presentation for more details. NR = not reached. Global interaction test not significant B#15Secondary endpoint: overall survival 28.6% maturity; trend towards improved OS with olaparib + abiraterone Probability of OS 15 1.0 0.9- 0.8- 0.7- 0.6 0.5 0.4 0.3 0.2 0.1 0.0 No. at risk Olaparib + abiraterone Placebo + abiraterone Events: 228. 10 12 14 16 18 20 22 24 26 28 30 Time from randomization (months) 4 399 398 398 394 391 387 385 379 374 369 364 359 349 343 333 322 316 313 290 263 231 193 159 135 116 92 73 51 37 24 11 397 394 392 386 385 383 381 377 374 371 368 363 353 345 335 322 314 308 286 258 223 186 151 121 104 88 63 44 22 13 6 0 0 2 4 6 8 32 1 0 COO 0 0 Events, n (%) Median OS (months) HR (95% CI) Olaparib + abiraterone (n=399) 107 (26.8) NR Placebo + abiraterone (n=397) 121 (30.5) NR 0.86 (0.66-1.12) P=0.29 Pre-specified 2-sided alpha: 0.001 3#16Secondary endpoints: TFST and PFS2 TFST and PFS2 results support longer-term benefit with olaparib + abiraterone Probability of not experiencing first subsequent therapy or death No. at risk 16 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.1 0.3 0.2 (months) 0.0 + 0 Olaparib + abiraterone Placebo + abiraterone Time to first subsequent therapy or death (TFST) *Nominal. Events, n (%) Median TFST HR (95% CI) 2 4 Olaparib + abiraterone (n=399) 183 (45.9) 6 25.0 Placebo + abiraterone (n=397) 221 (55.7) 8 10 12 14 16 Time from randomization (months) 53 399 398 396 385 374 365 358 345 338 328 317 308 295 285 272 260 250 245 222 202 174 148 124 104 87 67 397 394 390 377 368 354 345 329 319 313 303 292 273 261 250 231 222 214 191 174 147 121 98 76 63 53 38 19.9 0.74 (0.61-0.90) P=0.004* 18 20 22 24 26 41 28 28 25 12 19 6 eo 30 8 4 3 0 32 1 0 0 0 Probability of second progression-free survival No. at Risk 1.0 0.9- 0.8- 0.71 0.6 0.5 0.4 0.3 0.21 0.1 0.0 Olaparib + abiraterone. Placebo + abiraterone 0 Time to second progression or death (PFS2) Events, n (%) Median PFS2 (months) HR (95% CI) 2 4 st 6 Olaparib + abiraterone (n=399) 70 (17.5) 8 NR Placebo + abiraterone (n=397) 94 (23.7) NR 0.69 (0.51-0.94) P=0.0184* T T 10 12 14 16 18 20 22 24 26 28 30 Time from randomization (months) 399 396 387 383 372 366 353 347 338 326 318 311 300 297 291 284 282 279 261 237 209 177 148 126 106 85 68 49 34 22 10 397 394 381 374 367 363 351 346 339 322 320 312 300 294 286 276 269 259 239 212 179 152 124 99 85 71 50 36 18 11 5 888-O 4 0 32 1 0 0 0#17Overall safety profile A relatively small increase in discontinuations for olaparib vs placebo, discontinuation with abiraterone was similar between treatment arms n (%) Any AE Any AE CTCAE Grade 23 Death due to an AE Any AE leading to: Dose interruption of olaparib/placebo Dose reduction of olaparib/placebo Discontinuation of olaparib/placebo Discontinuation of abiraterone Olaparib + abiraterone (n=399) 387 (97.2) 188 (47.2) 16 (4.0) 17 AE = adverse event; AML = acute myeloid leukemia; CTCAE = Common Terminology Criteria for Adverse Events v4.03; MDS = myelodysplastic syndrome. 178 (44.7) 80 (20.1) 55 (13.8) 34 (8.5) Placebo + abiraterone (n=397) 376 (94.9) 152 (38.4) 17 (4.3) 100 (25.3) 22 (5.6) 31 (7.8) 35 (8.8) AEs of special interest for olaparib • No MDS/AML reported Incidence of new primary malignancies and pneumonitis were balanced between treatment arms B#18Cardiac and thromboembolic adverse events Cardiac failure and arterial thromboembolic events were balanced between the two arms Numerically higher venous thromboembolic events were reported for olaparib + abiraterone Pulmonary embolism was the most commonly reported venous thromboembolic event Pulmonary embolism events were mostly incidental findings by CT scans and did not lead to discontinuation of olaparib or abiraterone n (%) Cardiac failure SMQ Embolic and thrombotic events, arterial SMQ Embolic and thrombotic events, venous SMQ Pulmonary embolism 18 CT = computerised tomography; SMQ = Standardised MedDRA Query. Olaparib + abiraterone (n=399) 6 (1.5) 8 (2.0) 29 (7.3) 26 (6.5) Placebo + abiraterone (n=397) 5 (1.3) 10 (2.5) 13 (3.3) 7 (1.8) B#19Most common adverse events AE profile was consistent with the known toxicity profiles for the individual drugs Any 97.2 Anemia* Fatigue or asthenia Nausea Diarrhea Constipation Back pain Decreased appetite Vomiting Arthralgia Hypertension Dizziness Peripheral edema Urinary tract infection 100 80 Olaparib + abiraterone (n=399) Placebo + abiraterone (n=399) 47.2 38.4 46.0 60 37.2 28.1 40 15.1 17.3 17.3 17.1 14.6 13.1 0.8 1.0 1.0 2.3 1.5 0.3 0.3 12.6 0.8 0.3 9.3 12.8 12.6 3.5 10.8 10.3 10.3 2.0 20 3.3 0.3 00 1.0 3.3 16.4 6.3 13.9 5.8 0.3 9.1 0.5 17.7 16.4 0.3 11.4 1.0 7.8 18.4 20 28.3 40 60 80 94.9 100 Safety was assessed through the reporting of AEs according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v4.03) and laboratory assessments. 19 *Anemia category includes anemia, decreased hemoglobin level, decreased red-cell count, decreased hematocrit level, erythropenia, macrocytic anemia, normochromic anemia,normochromic normocytic anemia, and normocytic anemia. Grade 23 All grade Grade 23 All grade 3#20Conclusions 20 Olaparib + abiraterone led to a significant and clinically meaningful improvement in rPFS (HR 0.66 [95% CI 0.54-0.81]) over placebo + abiraterone in 1L mCRPC Benefit observed led to a median rPFS beyond 2 years Benefit was observed irrespective of HRRm status Secondary and exploratory endpoints support the treatment benefit of olaparib + abiraterone over placebo + abiraterone in the overall patient population The safety profile of olaparib + abiraterone was consistent with the safety profile for the individual drugs and there was no detriment to quality of life allowing most patients to stay on therapy The Phase III PROpel study is the first combination approach to deliver consistent clinical benefits for patients in the 1L mCRPC setting, irrespective of HRRm status 4#213 Opportunity and unmet need in mCRPC Dave Fredrickson Executive Vice President, Oncology Business Unit#22Prostate is the second most common cancer in male patients mCRPC therapies are limited; mostly monotherapy, including in first line NHA naïve at mCRPC ~50% NHA experienced in mCRPC ~50% Urologist-led Primary/ adjuvant Hormone sensitive Prostatectomy /RTX +/- Adjuvant ADT Biochemical recurrence ADT Urologists and oncologists mHSPC Recurrent ADT +/- docetaxel ADT + NHA De-novo ADT +/- docetaxel +/- RTX ADT + NHA nm CRPC doce- taxel/ other NHA Castration resistant Urologists and oncologists 1st-line metastatic HRRm 20-30%² HRRm 20-30% NHA or docetaxel NHA or docetaxel Lynparza (PROfound) NHA or docetaxel ~80% diagnosed here ~20% diagnosed here 22 Source: AstraZeneca estimates. Indicative populations. Not to scale 1. Rawla P. World J Oncol. 2019; 10(2):63-89. 2. Mateo, J, et al. New England Journal of Medicine, 2015, 373(18), pp.1697 - 1708. ADT = androgen deprivation therapy; RTX = radiation therapy; nmCRPC = non-metastatic castration resistant prostate cancer 2nd-line+ metastatic HRRm 20-30% Lynparza (PROfound) chemo/palliative care HRRm 20-30% chemo/palliative care chemo/palliative care 3#23PROpel - unprecedented clinical benefit without compromising quality of life - a potential new SoC in mCRPC Outcomes remain poor in advanced prostate cancer 40% of patients with prostate cancer will develop metastatic disease ¹-3 30% the 5-year survival rate for patients with metastatic disease4 3 years median OS for mCRPC patients in the first-line setting 5-9 50% of patients receive only one line of active therapy in mCRPC10 ● ● ● ● PROpel building on the success of PROfound Representative real-world population - simple trial design All-comers ITT population Retrospective HRR testing via tissue and ctDNA testing¹¹ Primary endpoint: radiographic progression free survival Key secondary endpoints: Overall survival, time to first subsequent therapy, time to second progression or death ● 300 Lynparza™ + abiraterone mg olaparib a potential new standard of care Clinically meaningful and consistent efficacy across subgroups Despite OS immaturity, strong secondary endpoint results provide confidence Class-leading tolerability - full 300mg Lynparza dose in combination with abiraterone Quality of life maintained, allowing adoption of upfront combination therapy 8.2-month median rPFS benefit over abiraterone alone 1. Beltran H, Beer TM, Carducci MA, et al. Eur Urol. 2011;60(2):279-290. 2. Sciarra A, Salciccia S. Eur Urol. 2014;65(5):905-906. 3. Sartor O, de Bono JS. N Engl J Med. 2018;378(7):645-657.4. Cancer of the Prostate - Cancer Stat Facts. SEER. Accessed November 6, 2019. 5. Kelly WK et al. J Clin Oncol. 2012;30:1534-40. 6. Quinn DI et al. Lancet Oncol. 2013;14:893-900. 7. Araujo JC et al. Lancet Oncol. 2013;14:1307-16.8. Ryan CJ et al. N Engl J Med. 2013;368:138-48.9. Beer TM et al. N Engl J Med. 2014;371:424-33. 10. Shore ND et al. Adv Ther. 2021;38:4520-40. 11. Tumour tissue and blood samples were collected at baseline for biomarker tests. HRRm status was determined 23 using a tumour tissue test (Foundation One® CDX) and/or a circulating tumour (ctDNA) based test (FoundationOneⓇLiquid CDx test). OS = overall survival; ITT = intent-to-treat.#2424 After almost a decade, the addition of Lynparza achieves a similar absolute rPFS improvement compared to the pivotal trial that established abiraterone as first-line SoC Median rPFS COU-AA-302¹ (2012) control abiraterone 8.2m 16.4m PROpel median rPFS Investigator assessment BICR HRRm Non-HRRm Dif. 8.2m 16.6m abiraterone 16.6m 13.9m 19.0m 16.4m abi 1. Mulders et al. N Engl J Med 2013; 368:138-148. Dif. = difference; NR = not reached; HR = hazard ratio. PROpel (2022) Lynparza + abiraterone 24.8m Lynparza + abiraterone 24.8m NR 24.1m 27.6m Dif. 8.2m HR 0.66 (0.54-0.81) 0.50 (0.34-0.73) 0.76 (0.60-0.97) 0.61 (0.49-0.74)#25PROpel: a new treatment approach in 1st-line mCRPC HRRm 20-30% 25 Other (~25%) 1st-line metastatic castration-resistant prostate cancer (mCRPC) - US patients NHA naive ~50% Receiving NHA (~75%) Lynparza + abiraterone (PROpel)¹ Prior NHA use ~50% Overall, ~65% of 1st-line mCRPC patients receive an NHA today Lynparza and abiraterone demonstrates a clear clinical benefit vs. abiraterone alone in first line patients who are NHA naïve Receiving NHA (~55%) Other (~45%) For NHA experienced patients, Lynparza and abiraterone offers a well tolerated, chemo-free treatment option Source: AstraZeneca estimates. 1. Pending health authority authorisation. The PROpel trial data is not currently approved in any jurisdiction. A clear option for NHA-naïve patients regardless of HRRm status The first combination trial to demonstrate consistent clinical benefit in 1st-line mCRPC 3#264 Other ASCO GU highlights Susan Galbraith Executive Vice President, Oncology R&D#27New advances in urothelial carcinoma Phase II data advancing understanding of this aggressive cancer 27 Imfinzi + Lynparza: Phase II BAYOU trial Platinum-ineligible patients with mUC Primary and secondary PFS analyses ITT population Median PFS, mo (95% CI) HR (95% CI) Log-rank p-value HRRm subset* Median PFS, mo (95% CI) HR (95% CI) Log-rank p-value D+O n=78 4.2 (3.6-5.6) D+PBO n=76 3.5 (1.9-5.1) 0.94 (0.64-1.39) 0.789 n=17 5.6 (1.9-8.1) n=14 1.8 (1.7-2.2) 0.18 (0.06-0.47) <0.001 Data suggests a role for PARP inhibition in HRRm UC mUC = metastatic urothelial carcinoma; UC = urothelial carcinoma; T-DXd = trastuzumab deruxtecan (Enhertu). Change in Sum of Diameters from Baseline, % 100 80 60 40 20 0 -20 -40 -60 -80 -100- Enhertu: Phase II U105 trial Combination with nivolumab Baseline 1 2 3 4 6 8 10 12 14 16 18 20 22 24 26 5 7 9 11 13 15 17 19 21 23 25 Time from First Dose of Study Drug, months Cohort 3 HER2 2+/3+ (n = 30) (part 2: 5.4 mg/kg T-DXd and nivolumab 360 mg) HER2+ UC included in DESTINY-PanTumor02#285 Closing and Q&A#29Investor Relations 29 Chris Sheldon [email protected] Tom Waldron [email protected] Christer Gruvris [email protected] Lauren Swales [email protected] Josie Afolabi [email protected] Morgan Sanford [email protected] Philip Sparks [email protected] Jen Kretzmann [email protected] 3#30A Appendix#3131 PROpel B#32Olaparib and abiraterone: A randomised Phase II trial Patients with mCRPC, unselected by HRRm status, with prior docetaxel treatment • Randomized 1:1 to full dose of olaparib + abiraterone vs placebo + abiraterone ● Statistically significant improvement in rPFS with olaparib + abiraterone, irrespective of HRRm status ¹ rPFS by HRRm subgroup²* Proportion of patients event-free Investigator-assessed rPFS¹ 1.0 0.8 0.6 0.4 0.2 0.0 0 3 6 8.2 A=5.6 I I 13.8 Events, n (%) 18 9 12 15 Time from randomization (months) 21 24 Ola + abi (n=71) 46 (65) HR 0.65 95% CI 0.44, 0.97; P=0.034 27 Abi (n=71) 54 (76) 30 HRRm n=23 (16%) HRRm partially characterized n=46 (32%) 1. Clarke N et al. Lancet Oncol 2018;19:975-86.2. Carr TH et al. Cancers 2021;13:5830 *Dashed line and shaded area show HR and 95% CI, respectively, for the intent to treat population. Please access the Supplement at https://bit.ly/3r50ms0 for more details including the full citations and further details on the HRRm partially characterised subgroup. Non-HRRm n=73 (51%) 0.25 0.62 I 1 I I I I I I 0.54 I I 1 0.95 0.50 HR (95% CI) 1.00 2.00 3#33ORR in patients with measurable disease 10% improvement in ORR with olaparib + abiraterone Rate (%) 70 60 50 40 30 20 10 0 T ORR 58.4% 54.0% PR 4.3% CR OR 1.60 (95% CI 1.02-2.53) P=0.0409* SD 26.1% PD 13.7% Olaparib + abiraterone (n=161) ORR 48.1% 41.9% PR 6.3% CR SD 28.1% PD 19.4% Placebo + abiraterone (n=160) 33 *Nominal. CR = complete response; OR = odds ratio; ORR = overall response rate; PD = progressive disease; PR = partial response; RECIST = Response Evaluation Criteria in Solid Tumors; SD = stable disease. 321/796 patients (40.3%) had measurable disease by RECIST v1.1 criteria at baseline B#34FACT-P quality of life over time Quality of life comparable between treatment arms Least-squares mean change from baseline in FACT-P total score* 20 15 10 5 0 -5 -10 -15 -20 H PH 5 Least-squares mean change from baseline in FACT-P total score* 41 45 49 53 Analysis visit (weeks) 9 13 17 21 25 29 33 37 → Olaparib + abiraterone (n=399) Placebo + abiraterone (n=397) 61 69 77 85 93 101 109 117 *Plot includes 95% confidence limits. FACT-P total score change from baseline values can be a minimum of -156 and a maximum of 156. A clinically meaningful change in FACT-P total score is 1015,16 34 FACT-P = Functional Assessment of Cancer Therapy-Prostate. 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