#1AstraZeneca B Investor science conference call: European Society for Medical Oncology (ESMO) Congress 2021 Conference call for investors and analysts 20 September 2021#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. Although the Group believes its expectations are based on reasonable assumptions, any forward-looking statements, by their very nature, involve risks and uncertainties and may be influenced by factors that could cause actual outcomes and results to be materially different from those predicted. 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Nothing in this document, or any related presentation/webcast, should be construed as a profit forecast. 2 B#3Speakers 3 Dr Sara Hurvitz Senior Investigator, DESTINY-Breast03 and Professor at David Geffen School of Medicine at UCLA Dave Fredrickson Executive Vice President, Oncology Business Unit Sunil Verma Vice President, Oncology R&D, Late-Stage Development Breast Cancer Susan Galbraith Executive Vice President, Oncology R&D Cristian Massacesi Chief Medical Officer & Oncology Chief Development Officer Chris Sheldon Vice President, Head of Investor Relations 3#4Agenda 4 1 Introduction: AstraZeneca @ ESMO 2021 2 3 4 5 Enhertu (T-DXd) Phase III DESTINY-Breast03 trial What's next for Enhertu? ESMO 2021 other highlights: Enhertu and Imfinzi Closing and Q&A#51 Introduction Susan Galbraith Executive Vice President, Oncology R&D 4#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 Infuse with engineered T cells Build synthetic immunity Cell therapy Targeted delivery of Oncolytic medicines that virus recruit immunity Diverse pipeline with potential for orthogonal combinations Build on PDx Overcome immune suppression 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 Epigenetics Nanomedicines Replacing standard of care (i.e., chemo) with targeted delivery of toxic molecules Reprogramming tumour cells B#7ESMO 2021 5 years of Presidential Symposia/Presentations 2019 FLAURA OS CCC00 MONARCH-2* PAOLA-1* PROfound 7 2017 PACIFIC FLAURA 2018 SOLO1 PALOMA-3* 2020 ADAURA PROfound OS 2021 DESTINY- Breast03 ● ● 65 abstracts with 20 oral presentations One Presidential presentation Eight Proffered paper oral presentations 11 Mini oral presentations 45 Posters 65 Abstracts Data highlights Enhertu in breast cancer DESTINY-Breast03 Enhertu in other cancers DESTINY-Gastric02, DESTINY-Lung01 Imfinzi COAST, CASPIAN, PACIFIC-R Tagrisso, Lynparza, datopotamab deruxtecan and capivasertib *Alliance presentations. Source: ESMO 2021 accepted abstracts. 23 additional presentations at ESMO 2021 will feature AstraZeneca medicines and potential new medicines but were not supported by AstraZeneca. 3#82 Enhertu (T-DXd) DESTINY-Breast03 Dr Sara Hurvitz Senior Investigator, DESTINY-Breast03 Phase III trial 4#9DESTINY-Breast03: An open-label, multicentre study (NCT03529110) Patients ● cancer Previously treated with trastuzumab and taxane in advanced/metastatic setting² • Could have clinically stable, treated brain metastases Stratification factors ● first randomised phase III trial of T-DXd Unresectable or metastatic HER2-positive¹ breast ● Hormone receptor status Prior treatment with pertuzumab History of visceral disease R 1:1 Interim analysis for PFS (data cutoff: May 21, 2021) • Efficacy boundary for superiority: P < 0.000204 (based on 245 events) IDMC recommendation to unblind study (July 30, 2021) Key secondary endpoint, OS: boundary for efficacy: P < 0.000265 (based on 86 events) T-DXd 5.4 mg/kg Q3W (n = 261) T-DM1 3.6 mg/kg Q3W (n = 263) Primary endpoint PFS (BICR) Key secondary endpoint OS Secondary endpoints ORR (BICR and investigator) ● DOR (BICR) • PFS (investigator) Safety ● ● T-DXd, trastuzumab deruxtecan; T-DM1, ado-trastuzumab emtansine; BICR, blinded independent central review; DOR, duration of response; HER2, human epidermal growth factor receptor 2; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; Q3W, every 3 weeks. 9 1. HER2 IHC3+ or IHC2+/ISH+ based on central confirmation. 2. Progression during or <6 months after completing adjuvant therapy involving trastuzumab and taxane. 3#10Patient disposition 10 Randomised to T-DXd (n = 261) Treated (n = 257) Ongoing study treatment (n = 132) Discontinued study treatment (n = 125) Death (n = 3) Adverse event (n = 35) Progressive disease (n = 66) ● ● ● ● ● ● Screened (n = 699) Clinical progression (n = 4) Withdrawal by subject (n = 13) Physician decision (n = 2) Other (n = 2) Randomised (n = 524) Randomised to T-DM1 (n = 263) Treated (n = 261) Ongoing study treatment (n = 47) Discontinued study treatment (n = 214) Death (n = 3) Adverse event (n = 17) Progressive disease (n = 158) ● ● ● ● ● Clinical progression (n = 12) Withdrawal by subject (n = 11) Physician decision (n = 8) Other (n = 5) Median follow up for T-DXd was 16.2 months and for T-DM1 was 15.3 months ● ●#11Best % Change in Sum of Diameters From Baseline Efficacy: confirmed ORR and best overall response 100 80 60 40- 20 0 -20- -40 -60 -80 -100 100 80 60 40 20 0 -20 -40- -60 -80 -100 T-DXd (n = 245)¹ T-DM1 (n = 228)¹ CI, confidence interval; CR, complete response; DCR, disease control rate; PD, progressive disease; PR, partial response; SD, stable disease. 1. Only subjects with measurable disease at baseline and at least one postbaseline target lesion assessment are included. 2. Based on BICR. 11 Red line at 20% indicates progressive disease; black line at -30% indicates partial response. Confirmed ORR n (%)² [95% CI] CR PR SD PD Not evaluable CR + PR + SD (DCR) T-DXd (n = 261) 208 (79.7) [74.3-84.4] T-DM1 (n = 263) 42 (16.1) 166 (63.6) 44 (16.9) 3 (1.1) 6 (2.3) 252 (96.6) 90 (34.2) [28.5-40.3] P<.0001 23 (8.7) 67 (25.5) 112 (42.6) 46 (17.5) 15 (5.7) 202 (76.8) 3#12Primary endpoint: PFS by BICR Progression-Free Survival probability, % 100 80 60 40 20 0 Patients Still at Risk: 0 Censor +T-DXd (n = 261) T-DM1 (n = 263) + 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 Time, months T-DXd (261) 261 256 250 244 240 224 214 202 200 183 168 164 150 132 112 105 79 64 T-DM1 (263) 263 252 200 163 155 132 108 96 93 78 65 60 51 43 37 34 29 23 Median PFS follow up for T-DXd was 15.5 months (range, 15.1-16.1) and for T-DM1 was 13.9 months (range, 11.8-15.1). 12 HR hazard ratio; INV, investigator; mo, month; NE, not estimable; NR, not reached. THI 18 19 53 21 mPFS, mo (95% CI) 12-mo PFS rate, % (95% CI) HR (95% CI) ||||| HHHHHH 20 21 45 36 29 12 8 16 ∞ 22 25 6 ++ 19 4 T-DXd NR (18.5-NE) 75.8 (69.8-80.7) 23 24 25 10 1 HH 6 1 26 27 LO 5 1 0.28 (0.22-0.37) P= 7.8 X 10-2² 3 1 28 T-DM1 6.8 (5.6-8.2) 34.1 (27.7-40.5) 2 1 29 30 0 1 0 1 31 32 00 0 1 0 B#13Secondary Endpoint: PFS by investigator assessment Progression-Free Survival probability,% 13 100 80 60 40 20 0 Patients Still at Risk: 0 + 1 Censor T-DXd (n = 261) T-DM1 (n = 263) 2 3 4 5 6 7 8 9 T-DXd (261) 261 256 250 244 240 224 214 202 T-DM1 (263) 263 252 200 163 155 132 108 96 200 183 93 78 10 11 12 13 168 164 65 60 150 132 51 43 15 16 17 18 Time, months 14 112 105 79 37 34 29 64 53 23 21 19 45 16 mPFS, mo (95% CI) 12-mo PFS rate, % (95% CI) HR (95% CI) 20 36 12 +HI 21 29 8 22 25 6 23 19 4 24 10 1 T-DXd 25.1 (22.1-NE) 76.3 (70.4-81.2) 25 6 1 26 LO 5 1 0.26 (0.20-0.35) P= 6.5 X 10-24 27 3 1 T-DM1 7.2 (6.8-8.3) 34.9 (28.8-41.2) 28 29 2 1 0 1 30 0 1 31 32 00 1 0 B#14Key secondary endpoint: overall survival 14 Overall survival probability, % 100 80 8 40 20 0 Patients Still at Risk: 0 Censor +T-DXd (n = 261) T-DM1 (n = 263) 4 2 3 + 1 5 6 7 T-DXd (261) 261 256 250 244 240 224 214 202 T-DM1 (263) 263 252 200 163 155 132 108 96 8 9 10 11 12 13 200 183 93 78 14 15 16 17 Time, months 18 19 ▬▬▬▬▬▬▬▬▬ +|||||||| H|#####+ 20 HHHHHH MOS, mo (95% CI) 12-mo OS rate, % (95% CI) HR (95% CI) 21 22 23 24 25 45 36 29 10 6 168 164 150 132 112 105 79 64 53 25 19 65 60 51 43 37 34 29 23 21 16 12 8 6 4 1 1 26 LO + +++ T-DXd NE (NE-NE) 94.1 90.3-96.4 27 ++ T-DM1 NE (NE-NE) 85.9 80.9-89.7 0.56 (0.36-0.86) P = .007172a 28 29 30 31 32 33 5 3 2 000 00 1 1 1 1 1 1 0 0 B Early OS data with relatively few events (33 in the T-DXd arm, 53 in the T-DM1 arm) a) P = .007172, but does not cross pre-specified boundary of P < .000265#1515 Drug-related TEAES in ≥20% of patients T-DXd (n = 257) System Organ Class Preferred term, n (%) Blood and lymphatic system disorders Neutropenia¹ Anemia² Leukopenia³ Thrombocytopenia4 Gastrointestinal disorders Nausea Vomiting Diarrhea Constipation General disorders Fatigues Investigations AST increased ALT increased Metabolism and nutrition disorders Decreased appetite Skin and subcutaneous tissue disorders Alopecia Any Grade 110 (42.8) 78 (30.4) 77 (30.0) 64 (24.9) 187 (72.8) 113 (44.0) 61 (23.7) 58 (22.6) 115 (44.7) 60 (23.3) 50 (19.5) 67 (26.1) Grade 23 49 (19.1) 15 (5.8) 17 (6.6) 18 (7.0) 17 (6.6) 4 (1.6) 1 (0.4) 0 13 (5.1) 2 (0.8) 4 (1.6) 3 (1.2) T-DM1 (n = 261) Any Grade 29 (11.1) 37 (14.2) 20 (7.7) 135 (51.7) 72 (27.6) 15 (5.7) 10 (3.8) 25 (9.6) 77 (29.5) 97 (37.2) 71 (27.2) 33 (12.6) Grade 23 8 (3.1) 11 (4.2) 1 (0.4) 65 (24.9) 1 (0.4) 1 (0.4) 1 (0.4) 0 2 (0.8) 13 (5.0) 12 (4.6) 0 93 (36.2) 1 (0.4) 6 (2.3) 0 Most drug-related TEAEs were gastrointestinal or haematological in nature Adverse events were managed according to the protocol. TEAE, Treatment emergent adverse events. 1. This category includes the preferred terms neutrophil count decreased and neutropenia 2. This category includes the preferred terms hamoglobin decreased, red blood cell count decreased, anemia, and hematocrit decreased 3. This category includes the preferred terms white blood cell count decreased and leukopenia 4.Tthis category includes platelet count decreased and thrombocytopenia 5. This category includes the preferred terms fatigue, asthenia, and malaise 6. Grade 1 alopecia: T-DXd = 26.5%, T-DM1 = 2.3%; grade 2, T-DXd = 9.3%.#16Adverse events of special interest Adjudicated as drug-related ILD/pneumonitis¹, n (%) n (%) Grade 1 Grade 2 Grade 4 T-DXd (n = 257) 7 (2.7) 0 18 (7.0) 1 (0.4) 0 T-DM1 (n = 261) 4 (1.5) There were no grade 4 or 5 adjudicated drug-related ILD/pneumonitis events observed with T-DXd LVEF, n (%) n (%) Grade 1 Grade 2 Grade 3 2 (0.8) 0 Grade 3 Grade 4 ILD, interstitial lung disease; LVEF, left-ventricular ejection fraction. 1. Patients with prior history of ILD/pneumonitis requiring steroids were excluded 2. Left ventricular dysfunction 3. Decreased ejection fraction. 16 Grade 5 0 0 Grade 5 T-DXd (n = 257) 1 (0.4)² 0 0 0 6 (2.3)³ 1 (0.4) ³ T-DM1 (n = 261) 0 0 0 0 In the T-DXd arm, all LVEF adverse events reported were asymptomatic and no cases of cardiac failure occurred Any Grade 27 (10.5) 5 (1.9) Any Grade 7 (2.7) 1 (0.4) 3#17Conclusions In the first randomised Phase III trial in breast cancer, T-DXd demonstrated: 17 Highly clinically meaningful and statistically significant improvement in PFS compared with T-DM1 in patients with HER2-positive mBC PFS HR of 0.28 (P = 7.8 x 10-22) • Consistent benefit seen across key subgroups and efficacy endpoints, with a confirmed ORR for T-DXd of 79.7% vs 34.2% for T-DM1 (CR, 16.1% vs 8.7%) ● Encouraging OS trend at the time of first interim analysis 12-month OS rate for T-DXd was 94.1% vs 85.9% for T-DM1 A safety profile that is comparable between the two arms Similar rates of all grade and grade 23 drug-related TEAEs between arms • There were no grade 4 or 5 ILD/pneumonitis events in either arm ● These data support T-DXd becoming the standard of care for 2L HER2-positive mBC mBC, metastatic breast cancer.#18T-DXd transforms the treatment paradigm for patients with metastatic HER2+ breast cancer 18 Second-line monotherapy data that rivals first-line current standard triplet therapy Consistency across all sub-groups Improved safety profile 1L 1L 2L 2L+ 3L+ Trastuzumab + pertuzumab + taxane, CLEOPATRA¹: mPFS = 18.7 months T-DM1 + pertuzumab, MARIANNE²: mPFS = 15.2 months T-DXd DESTINY-Breast03³: mPFS = not yet reached Investigator-assessed PFS: 25.1 months T-DM1, EMILIA4: mPFS = 9.6 months T-DXd DESTINY-Breast015: mPFS = 19.4 months 1. Swain SM, Baselga J et al. N Engl J Med. 2015;372:724-34. 2. Perez J et al. Expert Opin Biol Ther. 2021;21:811-24 3. Cortés, J, Presented at ESMO 2021, Abstract LBA1 on 18 September 2021. 4. Verma S et al. N Engl J Med. 2012;367:1783-91 5. DB01: Modi S et al. Presented at San Antonio Breast Cancer Symposium. 2020. Poster PD3-06.#193 What's next for Enhertu? Dave Fredrickson Executive Vice President, Oncology Business Unit 4#20Enhertu: a new standard of care for patients with HER2-positive metastatic breast cancer 20 ● ● Today: 3rd-line+ mBC Strong launch trajectory: market leader in every major country launched¹ >7,000 patients treated to date Partnering with healthcare practitioners with treatment-specific guidance 1. UK National Health Service - Cancer Drugs Fund, AstraZeneca market studies. 2022: 2nd-line mBC DESTINY-Breast03: unprecedented benefit in 2nd line ● • Consistent efficacy across all sub-groups Safety profile and prolonged PFS benefit supports extended duration on therapy ● Future: earlier settings, combinations Efficacy and safety profile support development in 1st line and adjuvant settings Opens opportunity to treat with curative intent • An Enhertu option for every patient with HER2+ cin breast cancer ENHERTU#21Enhertu in breast cancer and beyond Opportunities across treatment settings HER2-positive breast cancer HER2-low breast cancer Beyond breast cancer neo-adjuvant / adjuvant post neo-adjuvant neo-adjuvant replace chemo + trastuzumab + pertuzumab replace T-DM1 adjuvant replace chemo + trastuzumab + pertuzumab HR+: chemotherapy ± endocrine therapy 1st-line metastatic replace chemotherapy + trastuzumab + pertuzumab HR-: chemotherapy +/- 10 endocrine + CDK4/6i 2nd-line metastatic replace T-DM1 and other standard of care 3rd-line metastatic replace/displace chemotherapy and endocrine combinations¹ replace/displace chemotherapy and evaluate combinations broaden in gastric cancer and expand into NSCLC, CRC and other cancers 21 HR = hormone-receptor positive; CDK4/6i = cyclin-dependent kinase 4/6 inhibitor; HR- = hormone-receptor negative; 10 = immuno-oncology. NSCLC = non-small cell lung cancer; CRC = colorectal cancer. 1. in endocrine therapy refractory/resistant patients. A#224 Other ESMO 2021 highlights - Enhertu and Imfinzi Susan Galbraith Executive Vice President, Oncology R&D 4#23100% Percentage of Patients Enhertu: extending clinical benefit to other cancers 80% 60% 40% 20% 0% No. at Risk: 23 Phase II DESTINY-Lung01 Robust and durable anti-cancer activity in patients with previously treated HER2m NSCLC Overall Survival ++ Median OS: 17.8 months (95% CI, 13.8-22.1) 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 Months 91 89 88 86 82 77 75 75 70 68 65 58 51 46 36 29 25 22 19 19 17 15 14 13 13 10 7 5 Median PFS follow-up for T-DXd was 15.5 months (range, 15.1-16.1) and for T-DM1 was 13.9 months (range, 11.8-15.1) Dashed lines indicate the 95% CI. Of 91 patients, 47 had died by the cutoff date. Data for 44 patients were censored as indicated by tick marks; patients were censored if they discounted treatment. 3 1 0 Best % Change in Sum of Diameters from Baseline 60- 40- 20+ -20- -40- -60- -80- -100- Phase II DESTINY-Gastric02 Efficacy results demonstrate clinically meaningful and durable responses Best Percentage Change of Tumour Size from Baseline Confirmed ORR: 38% (95% CI, 27.3-49.6) Subjects T-DXd 6.4 mg/kg (N = 79) ¹ 3#24Enhertu: an extensive clinical development programme Focusing on HER2+ and HER2-low breast cancer and other cancers 24 Breast cancer Gastric cancer Lung, CRC and other cancers HER2+ HER2 Low HER2+ HER2 mutated HER2 expressing Post-neoadjuvant/ Adjuvant DESTINY-Breast05 Ph III 1st line DESTINY-Breast07 Ph Ib/II (Part 2) DESTINY-Breast09 Ph III BEGONIA Ph II DESTINY-Lung04 Ph III DESTINY-Lung03 Ph Ib DESTINY-Breast03 Ph III 2nd line DESTINY-Breast06 Ph III DESTINY-Breast08 Ph lb DESTINY-Gastric03 Ph lb/Il DESTINY-Gastric02 Ph II DESTINY-Gastric04 Ph III DESTINY-Lung02 Ph II DESTINY-PanTumor01 Ph II DESTINY-Lung01 Ph II HUDSON Ph II DESTINY-PanTumor02 Ph II 3rd line+ DESTINY-Breast01 Ph II DESTINY-Breast02 Ph III DESTINY-Breast07 Ph Ib/II (Part 1) DESTINY-Breast04 Ph III DESTINY-Gastric01 Ph II DESTINY-Gastric06 Ph II DESTINY-CRC01 Ph II DESTINY-CRC02 Ph II monotherapy combination 3#25Imfinzi in Stage III, unresectable non-small cell lung cancer Cementing leadership in this potentially curative setting PACIFIC-R: Real world PFS Imfinzi after CRT for a median duration of ~11 months is effective in a large, real-world cohort of patients with unresectable Stage III NSCLC PFS Total events, N (%) Progression per RECIST Progression per physician assessment Progression, assessment unknown Deaths in absence of progression Median PFS, months 95% CI PFS rate, % 12 months 24 months PACIFIC-R FAS N=1,399 737 (52.7) 456 (32.6) 170 (12.2) 30 (2.1) 81 (5.8) 21.7 19.2-24.5 62.4 48.2 PACIFIC trial (durva. arm)¹ N=476 268 (56.3)* 16.9 13.0-23.9 55.7 45.0 1. Spigel DR, et al. J Clin Oncol 2021;39(15_suppl):8511. *Range for median follow-up duration = 0-35.6 months; *In the PACIFIC trial, PFS was assessed by BICR per RECIST v1.1; * Per local regulations. FAS, full analysis set; rw, real-world; UK, United Kingdom. 25 PFS probability COAST: PFS by investigator's analysis First randomised Phase II to show evidence of improved outcomes with novel 10 combinations in the PACIFIC setting 1.0 0.9 0.8 0.7 765432 0.6 0.5 o o o o 0.4 0.3 0.2 0.1 0 No. at risk D O. 0 67 60 D+O D+M 62 T 2 50 49 55 4 32 46 46 Events/patients, n mPFS, months (95% CI)¹ HR (95% CI)2,3 32 40 44 20 37 41 D 38/67 6.3 (3.7-11.2) 72.7% 6 8 10 Time from randomisation (months) 16 30 35 64.8% 39.2% T 12 14 13 22 25 9 13 11 H||| T 16 D+O 22/60 NR (10.4-NE) 0.44 (0.26-0.75) 7 9 6 T 18 3 5 1 20 0 0 1 D+M 21/62 15.1 (13.6-NE) 0.65 (0.49-0.85) Data cut-off: 17 May 2021 (median follow-up of 11.5 months; range, 0.4-23.4) D, durvalumab; M, monalizumab; O, oleclumab. 1. Interim analysis performed when all patients had a 10mth min potential follow-up; Kaplan-Meier estimates for PFS, PFS rate and 95% Cls 2. PFS HR and 95% CI estimated by Cox regression model, stratified by histology (adenocarcinoma and non- adenocarcinoma) 3. Compared with the 67 and 64 patients in the D arm enrolled concurrently with patients in the D+O and D+M arms, respectively.#26Imfinzi: extending IO leadership through portfolio combinations 26 Change in target lesion from baseline (%) Probability of overall survival 1.0 0.8 0.6 0.4 120- 0.2 100- 80- 60- 40- 20 0 -20- -60- -80- -100- ADCs POC: BEGONIA mBC 1L HER2-low/HR- 0 0 6 12 18 9 24 30 CTLA4 POC: POSEIDON (adv NSCLC)/Study 22 (HCC)/MEDI5752 Ph II 12 36 42 15 Time (weeks) 48 18 21 Time (months) 54 24 Best response Partial response Stable disease RECIST progression. New lesion S22 (adv HCC): Treme 300mg + Imfinzi vs. Imfinzi 60 27 66 30 72 33 36 39 CD73, NKG2A POC: COAST - Stg III UR NSCLC (below) / Study 5 (PDAC) PFS probability 1.0 0.9- 0.8- 0.7- 0.6- 0.5- 0.4- 0.3- 0.2- 0.1- 0 No. at risk 0 D 67 60 62 D+O D+M 2 50 49 55 BIOSCIENCES 4 32 46 46 32 40 44 6 8 10 12 14 Time from randomisation (months) 20 37 41 TIGIT >compugen FROM CODE TO CURE T 72.7% 16 30 35 64.8% 39.2% 13 22 h 25 9 13 11 H||| 16 7 9 6 T 18 AZD2936 3 5 1 20 0 0 1 Imfinzi + domvanalimab Phase III (PACIFIC-8) Phase I/II (ARTEMIDE-01) PARP inhibitor POC: MEDIOLA BRCAwt PSR ovarian (below) / BAYOU (UC) Best % change in targetlesion size 100- 80- 60- 40- 20- 0 -20- -40- -60- -80- Survival Probability -100 1.0- ATR inhibitor POC: PDX relapse - HUDSON adv NSCLC (below)/VIKTORY adv M 09- 08- 07- 06- 0.5- 04- 03- 02- 01- Lynparza + Imfinzi + bevacizumab 00- Confirmed ORR = 77.4% (95% CI 58.9-90.4) Censored ADCs antibody drug conjugates; CD73 = cluster of differentiation 73; NKG2A = natural killer group 2 member A; PARPI = poly (ADP-ribose) polymerase; CTLA4 = cytotoxic T-lymphocyte-associated protein 4; HCC = hepatocellular carcinoma; TIGIT = T cell immunoreceptor with Ig and ITIM domains; ATR = ataxia telangiectasia and rad3-related; POC = proof of concept; UR = unresectable; NSCLC = non small cell lung cancer; BRCAwt = breast cancer gene wildtype; PSR = platinum sensitive relapsed; PDAC = pancreatic ductal adenocarcinoma; UC = urothelial cancer; adv = advanced. 18 Time (months) ORR = 87.1% (95% CI 70.2-964) Median DOR = 11.1 months (IQR 7.4-164) 27 olaparib danyatirsen ceral asertib oledumab 33 36 4#275 Closing and Q&A 4#28Investor Relations 28 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] A#29A Appendix 4#30Enhertu: DESTINY-Lung01 trial design Multi-centre, international, 2-cohort Phase II trial (NCT03505710) Key eligibility criteria Unresectable/metastatic ● ● ● ● ● ● nonsquamous NSCLC Relapsed from or is refractory to standard treatment ● Measurable disease by RECIST v1.1 Asymptomatic CNS metastases at baseline¹ ECOG PS of 0 or 1 Locally reported HER2 mutation (for Cohort 2)² Cohort 1: HER2-overexpressing³ (IHC 3+ or IHC 2+) T-DXd 6.4 mg/kg q3w N = 49 Cohort 2: HER2-mutated T-DXd 6.4 mg/kg q3w N = 42 Cohort 1a: HER2-overexpressing³ (IHC 3+ or IHC 2+) T-DXd 5.4 mg/kg q3w N = 41 Cohort 2 expansion: HER2-mutated T-DXd 6.4 mg/kg q3w N = 49 Data cutoff: May 3, 2021 • 91 patients with HER2m NSCLC were enrolled and treated with T-DXd 15 patients (16.5%) remain on treatment to date 76 patients (83.5%) discontinued, primarily for progressive disease (37.4%) and adverse events (29.7%) Primary end point Confirmed ORR by ICR4 Secondary end points • DOR • PFS • OS • DCR ● Safety Exploratory end point Biomarkers of response 1. Patients with asymptomatic brain metastases not requiring ongoing steroid or anticonvulsant therapy were allowed to enrol 2. HER2 mutation documented solely from a liquid biopsy could not be used for enrolment 3. HER2 overexpression without known HER2 mutation was assessed by local assessment of archival tissue and centrally confirmed 4. Per RECIST v1.1 30 ECOG PS= Eastern Cooperative Oncology Group performance status; ICR = independent central review; IHC = immunohistochemistry; q3w, every 3 weeks; RECIST v1.1, Response Evaluation Criteria in Solid Tumours version 1.1. 3#31Enhertu: DESTINY-Gastric02 trial design Open-label, multicentre Phase II trial in Western patients with HER2+ gastric or GEJ cancer (NCT04014075) ● ● ● Key eligibility criteria Pathologically documented, unresectable or metastatic gastric or GEJ cancer Centrally confirmed HER2 positive disease (defined as IHC 3+ or IHC 2+/ISH+) on biopsy after progression on first-line trastuzumab-containing regimen • ECOG PS 0 or 1 T-DXd 6.4 mg/kg Q3W N = 79¹ Primary endpoint ● Secondary endpoints² PFS by ICR OS ● ● Confirmed ORR by ICR ● DOR by ICR Safety and tolerability DESTINY-Gastric02 is the first study focused only on second-line T-DXd monotherapy in Western patients with HER2+ gastric/GEJ cancer who have progressed on a trastuzumab-containing regimen It is the follow-on study to DESTINY-Gastric01, which evaluated T-DXd third-line or later in Asian patients³ Patients were enrolled in Europe (Belgium, Great Britain, Italy, Spain) and the United States (data cutoff: April 9, 2021) 1. Enrollment of 80 patients was planned; actual enrollment was 79 patients 2. Other secondary endpoints were ORR, PFS, and DOR by investigator assessment, pharmacokinetics, anti-drug antibodies, and patient-reported outcomes 3. Shitara K et al. N Engl J Med. 2020;382:2419-30. 31 GEJ = gastroesophageal junction; ISH = in situ hybridisation. B#32Imfinzi: COAST trial design A Phase II, randomised open-label trial 32 ● ● ● Locally advanced, unresectable, Stage III NSCLC No progression after prior CCRT ECOG PS 0 or 1 N=189 randomised 1-42 days post-cCRT IV = intravenous; PK = pharmacokinetics. Randomised 1:1:1 Stratification by histology (adenocarcinoma and non-adenocarcinoma) Study treatment up to 12 months CONTROL Durvalumab 1500 mg IV monotherapy Q4W ARM A Durvalumab 1500 mg IV Q4W + oleclumab 3000 mg IV Oleclumab Q2W for cycles 1 and 2, then Q4W starting cycle 3 ARM B Durvalumab 1500 mg IV Q4W + monalizumab 750 mg IV Q2W Primary Endpoint ORR by investigator assessment (RECIST v1.1) Secondary Endpoints • Safety • DOR • DCR • PFS by investigator assessment (RECIST v1.1) • OS . • PK Immunogenicity A planned sample size of 60 patients per arm was designed to provide acceptable precision in estimating antitumour activities in an early phase setting Between Jan 2019 and Jul 2020, 189 patients were randomised of whom 186 received D (n=66), D+O (n=59) or D+M (n=61) As of 17 May 2021, all patients had a minimum of 10 months potential follow-up and the median actual follow-up was 11.5 months (range, 0.4-23.4; all patients) ● B#3333 Imfinzi: Propensity score matching of COAST (durvalumab arm) with PACIFIC (durvalumab arm) ● Matching variables: Age (<75, ≥75), Race (Asian, Other), Prior therapy (Carboplatin, Cisplatin), Time from last radiation to randomisation (<14 days, >14 days), Best response to prior therapies (PR, SD) and Disease stage at entry (IIIA, IIIB, IIIC) PFS probability 1.0 0.8 0.6 0.4 0.2 0.0 COAST PACIFIC 0 61 61 COAST (durva) 6 Ni m 25 31 PACIFIC (durva) 12 18 +++# +++H 12 18 24 Time from randomisation (months) NW 0 7 H 30 1 Events/patients, n PFS-10 months (95% CI) ORR (conf + unconf), % (n) 36 0 COAST (D) 32/61 38.0% (24.5-51.3%) 24.6% (15) PACIFIC (D) 31/60 44.6% (31.3-57.1%) 24.6% (15) B#3434 Use of AstraZeneca slides from conference calls and webcasts The AstraZeneca webcast, conference call and presentation slides (together the 'AstraZeneca materials') are for your personal, non-commercial use only. 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