#1B AstraZeneca Full-year and Q4 2021 results Conference call and webcast for investors and analysts 10 February 2022#22 Forward-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. The forward-looking statements reflect knowledge and information available at the date of preparation of this document and the Group undertakes no obligation to update these forward-looking statements. The Group identifies the forward-looking statements by using the words 'anticipates', 'believes', 'expects', 'intends' and similar expressions in such statements. Important factors that could cause actual results to differ materially from those contained in forward-looking statements, certain of which are beyond the Group's control, include, among other things: the risk of failure or delay in delivery of pipeline or launch of new medicines; the risk of failure to meet regulatory or ethical requirements for medicine development or approval; the risk of failure to obtain, defend and enforce effective IP protection and IP challenges by third parties; the impact of competitive pressures including expiry or loss of IP rights, and generic competition; the impact of price controls and reductions; the impact of economic, regulatory and political pressures; the impact of uncertainty and volatility in relation to the UK's exit from the EU; the risk of failures or delays in the quality or execution of the Group's commercial strategies; the risk of failure to maintain supply of compliant, quality medicines; the risk of illegal trade in the Group's medicines; the impact of reliance on third-party goods and services; the risk of failure in information technology, data protection or cybercrime; the risk of failure of critical processes; any expected gains from productivity initiatives are uncertain; the risk of failure to attract, develop, engage and retain a diverse, talented and capable workforce; the risk of failure to adhere to applicable laws, rules and regulations; the risk of the safety and efficacy of marketed medicines being questioned; the risk of adverse outcome of litigation and/or governmental investigations; the risk of failure to adhere to increasingly stringent anti-bribery and anti-corruption legislation; the risk of failure to achieve strategic plans or meet targets or expectations; the risk of failure in financial control or the occurrence of fraud; the risk of unexpected deterioration in the Group's financial position; and the impact that the COVID-19 global pandemic may have or continue to have on these risks, on the Group's ability to continue to mitigate these risks, and on the Group's operations, financial results or financial condition. Nothing in this document, or any related presentation/webcast, should be construed as a profit forecast. B#33 Speakers Pascal Soriot Executive Director and Chief Executive Officer Dave Fredrickson Executive Vice President, Oncology Business Ruud Dobber Executive Vice President, BioPharmaceuticals Business Marc Dunoyer Chief Executive Officer, Alexion Aradhana Sarin Executive Director and Chief Financial Officer Susan Galbraith Executive Vice President, Oncology R&D Mene Pangalos Executive Vice President, BioPharmaceuticals R&D Leon Wang Executive Vice President, International (for Q&A) 4#4Agenda 4 Opening remarks 2 Financial results Oncology 1 3 4 5 6 BioPharmaceuticals, Emerging Markets Rare Disease Closing remarks and Q&A#51 Opening remarks Pascal Soriot Chief Executive Officer $#6Full year and Q4 2021: key updates Continuing to deliver on our strategic objectives Robust growth Exceeded FY 2021 revenue guidance Total Revenue $37.4bn (+38%) $33.4bn (+23%) excluding FY 2021 Vaxzevria¹ revenue - - $35.2bn (+30%) including Q4 2021 Vaxzevria¹ revenue • Core EPS $5.29 (+37%) ● Broad-based performance Delivering value to patients Oncology $13.7bn (+17%) BioPharmaceuticals: CVRM $8.0bn (+9%) Respiratory & Immunology $6.0bn (+9%) Other medicines $2.5bn (-7%) COVID-19 $4.1bn (n/m) • Rare Disease² $3.1bn (+9%) Science-led innovation Strong Q4 2021 performance Tezspire US approval - severe asthma Evusheld US EUA - COVID-19 prophylaxis Lynparza US Priority Review - adjuvant breast cancer Saphnelo EU CHMP recommendation - systemic lupus erythematosus • Ultomiris US Priority Review - generalised myasthenia gravis FY 2021: Total Revenue $37.4bn (+38%) | Core EPS of $5.29 (+37%) Absolute values at actual exchange rates; changes at constant exchange rates (CER) and for year-to-date (YTD) December 2021, unless stated otherwise. CVRM = Cardiovascular, Renal and Metabolism; COVID-19 = coronavirus disease 2019; CHMP = Committee for Medicinal Products for Human Use; EUA = Emergency Use Authorisation; n/m = growth rate not meaningful. 1. Vaxzevria Total Revenue' also includes Collaboration Revenue from sub-licensees 6 that produce and supply the AstraZeneca COVID-19 Vaccine under their own trademarks. 2. FY 2021 revenues from date of acquisition closing, 21 July 2021 through 31 December 2021; pro forma growth rates calculated by comparison post-acquisition revenues with the corresponding prior year revenues adjusted pro-rata to match the post-acquisition period.#7Full year and Q4 2021: performance Oncology, CVRM, R&I and Rare Disease all delivered strong growth Growth across geographies (excluding Vaxzevria) Q4 2021 $m Oncology CVRM Respiratory & Immunology Rare Disease¹ Other medicines Evusheld Total revenue excl. Vaxzevria Vaxzevria² Total Revenue Growth across disease areas FY 2021 $m 13,663 8,034 6,049 3,071 2,484 135 33,436 3,981 37,417 CER growth % 17 9 (7) n/m 23 n/m 38 Q4 2021 $m 3,919 2,007 1,593 1,760 835 135 10,250 1,762 12,011 CER growth % 21 8 3 11 14 n/m 39 n/m 63 US EM - EM excl. China - China Europe Established Rest of World Total revenue excl. Vaxzevria Vaxzevria² Total revenue FY 2021 $m 12,164 9,977 3,977 6,000 7,015 4,280 33,436 3,981 37,417 CER growth % 38 10 21 22 21 23 n/m 38 Total revenue at actual exchange rates; changes at CER. R&I= Respiratory and Immunology; EM = emerging markets. 1. FY 2021 revenues from date of acquisition closing, 21 July 2021 through 31 December 2021; growth rates 7 calculated by comparison post-acquisition revenues with the corresponding prior year revenues adjusted pro-rata to match the post-acquisition. 2. Vaxzevria Total Revenue also includes Collaboration Revenue from sub-licensees that produce and supply the AstraZeneca COVID-19 Vaccine under their own trademarks. 3,859 2,498 1,197 1,301 2,573 1,320 10,250 1,762 12,011 CER growth % 62 10 38 (9) 42 47 39 n/m 63#8AstraZeneca: 2022-2025 Industry leading double-digit growth Durable growth drivers through 2025 including multiple blockbuster-medicines Oncology SIMFINZIⓇ durvalumab Injection for Intravenous Use 50 mg/ml CALQUENCE® (acalabrutinib) 100 mg capsules Lynparza® olaparib tablets 150 mg TAGRISSOⓇ osimertinib ENHERTU fam-trastuzumab deruxtecan-nxki 20 mg/mL INJECTION FOR INTRAVENOUS USE CVRM 19.0 farxiga (dapagliflozin) 5mg & 10mg LOKELMA sodium zirconium cyclosilicate powder for oral suspension R&I Fasenra (benralizumab) injection 30 mg BREZTRI AEROSPHERE® (budesonide 160 mcg. glycopyrrolate 9 mcg and formoterol fumarate 4.8 mcg) Inhalation Aerosol TEZSPIRE™ (tezepelumab-ekko) in 210 mg V&I EVUSHELD tixagevimab, cilgavimab Vaxzevria COVID-19 Vaccine (ChAdOx1-S [recombinant]) Rare Disease ULTOMIRIS [ravulizumab-cwvZ) injection for intravenous use SOLIRIS (eculizumab). Injection for Intravenous Use 300 mg/30 mL vial Strensiq (asfotase alfa) 40, for injection mg/mL Rare 17% R&I 16% Other 9% Diversification of disease areas and geographies Q4 2021 Total Revenue¹ Oncology 38% CVRM 20% Est. Row 13% Europe 25% 8 1. Total revenue excluding Vaxzevria. Evusheld is included in other. V&I = Vaccines and Immune Therapies. V&I will be a new reporting line within BioPharmaceuticals from Q1 2022, and will contain the following medicines, Vaxzevria, Evusheld, FluMist, Synagis and potential new medicine nirsevimab, which is being developed in collaboration with Sanofi. Emerging Markets 24% US 38% B#9AstraZeneca: 2025+ Delivering growth through innovation Robust life-cycle management Supports durable, growing revenue base 90 farxiga (dapagliflozin) CALQUENCE® (acalabrutinib) 100 mg capsules TAGRISSO osimertinib ULTOMIRIS (ravulizumab-cwvZ] SIMFINZIⓇ durvalumab Injection for Intravenous Use 50 mg/ml DENHERTUⓇ fam-trastuzumab deruxtecan-nxki 20 mg/mL INJECTION FOR INTRAVENOUS USE Lynparza olaparib Fasenra (benralizumab) on 30 mg Innovative late-stage pipeline Continued investment in clinical stage pipeline 15 NMES in Phase III 128 NME or major LCM projects in Phase II and III Across a number of areas of high unmet need, with first or best in class potential Strategic business development ● Recent clinical stage business development • Rare Disease (Alexion) Dato-DXd (Daiichi Sankyo) Eplontersen (lonis) • CAEL-101 (Caelum Bio) ● NI006 (Neurimmune) Attractive LoE profile US LOE for selected medicines Ultomiris Dato-Dxd Enhertu Tagrisso Calquence Imfinzi Lynparza Soliris Farxiga Brilinta 2020 9 LCM = life-cycle management; NME = new molecular entity; Dato-DXd = datopotamab deruxtecan; LoE = loss of exclusivity. *Amgen IPR settled to grant Amgen a non-exclusive, royalty-free license to sell an eculizumab product in the US from March 1, 2025. 2025 2030 B#10Late-stage pipeline delivery Important milestones since Q3 2021 update Regulatory approvals or other regulatory action Regulatory submissions or acceptances Major Phase III data readouts or other significant developments Medicine Saphnelo Tezspire Evusheld Lynparza Lynparza Lynparza Lynparza Enhertu Enhertu Imfinzi +/- tremelimumab Koselugo Ultomiris Ultomiris Vaxzevria / AZD2816 Lynparza Lokelma eplontersen Indication / Event systemic lupus erythematosus: CHMP positive opinion severe asthma COVID-19 prophylaxis: emergency use authorisation breast cancer (adjuvant, BRCAm): priority review breast cancer (adjuvant, BRCAm): regulatory submission ovarian cancer (1st-line): regulatory submission prostate cancer (1st-line): regulatory submission HER2-positive breast cancer (2nd-line): priority review HER2-positive breast cancer (2nd-line): regulatory submission NSCLC (1st-line): regulatory submission NF1-PN: regulatory submission Geography COVID-19: phase III primary endpoint met breast cancer (adjuvant, BRCAm): orphan drug designation chronic haemodialysis with hyperkalaemia: fast track designation transthyretin amyloidosis: orphan drug designation EU US US US EU, JP CN EU US EU, JP US, EU, JP JP subcutaneous formulation in PNH and aHUS: regulatory submission US generalised myasthenia gravis: priority review US JP US US 10 HER2-positive = human epidermal growth factor receptor 2 positive; BRCAm = breast cancer susceptibility gene 1/2 mutation; NSCLC = non-small cell lung cancer; NF1-PN = neurofibromatosis type 1 with plexiform neurofibromas; PNH = paroxysmal nocturnal haemoglobinuria; aHUS = atypical haemolytic uraemic syndrome. Status as of 10 February 2022.#112 Financial results Aradhana Sarin Chief Financial Officer www. ******#12Reported profit and loss Total Revenue - Product Sales - Collaboration Revenue Gross margin Operating expenses¹ - R&D expenses - SG&A expenses Other operating income Operating profit Tax rate EPS FY 2021 $m 37,417 36,541 876 66.0% 25,416 9,736 15,234 1,492 1,056 143.4% $0.08 CER change % 38 38 20 (12.6) pp 40 59 32 (4) (70) (84) % total revenue 100 98 2 68 26 41 4 3 Q4 2021 $m 12,011 11,498 513 59.8% 7,825 2,584 5,117 147 (292) 45.6% ($0.22) 12 Absolute values at actual exchange rates; changes at CER. Gross margin excludes the impact of collaboration revenue and any associated costs, thereby reflecting the underlying performance of product sales. 1. Includes distribution expenses. R&D = research and development; SG&A = sales, general and administration; pp = percentage points; n/m = growth rate not meaningful. CER change % 63 65 29 (16.0) pp 55 50 59 (78) (105) (113) % total revenue 100 96 4 65 22 43 1 (2) 4#13Core profit and loss Core EPS above FY 2021 guidance Total Revenue - Product Sales - Collaboration Revenue Gross margin Operating expenses¹ - R&D expenses - SG&A expenses Other operating income Operating profit Tax rate EPS FY 2021 $m 37,417 36,541 876 74.2% 19,537 7,987 11,104 1,492 9,928 16.6% $5.29 CER change % 38 38 20 (4.7) pp 22 33 15 (4) 41 37 % total revenue 100 98 2 52 21 30 4 27 Q4 2021 $m 12,011 11,498 513 74.3% 5,888 2,396 3,368 146 3,318 16.2% $1.67 13 Absolute values at actual exchange rates; changes at CER. Gross margin excludes the impact of collaboration revenue and any associated costs, thereby reflecting the underlying performance of product sales. 1. Includes distribution expenses. R&D = research and development; SG&A = sales, general and administration; pp = percentage points; n/m = growth rate not meaningful. CER change % 63 65 29 (1.9) pp 26 40 18 (78) 94 74 % total revenue 100 96 4 49 20 28 1 28#142022 Guidance Continuing to drive innovation and growth Total revenue guidance $Bn 45 40 35 30 25 20 15 10 5 0 Grow by high-teens % -2% 2018 +13% +10% +38% 2019 2020 2021 2022E 14 Growth rates at CER. 2022 guidance range Grow by mid-to-high twenties % 8 7 6 5 4 3 2 1 Core EPS guidance 0 -19% +0% || 2018 2019 +18% 2020 +37% 2021 2022E Headwinds Ongoing pricing pressure in China, mid single-digit revenue decline anticipated COVID-19 still impacting diagnosis and treatment rates, particularly in Oncology Decline in COVID-19 therapies revenue expected in 2022 Intensified competition for some legacy medicines Continued pricing pressure in many markets Tailwinds First full year of Alexion ownership Strong ex-China Emerging markets growth Continued strong uptake for key medicines e.g. Farxiga, Tagrisso, Calquence and Enhertu Unique opportunity for Evusheld to provide protection against COVID-19 in vulnerable patients Growth supported by a diversified business model across key disease areas and geographies#15Net debt and capital allocation priorities FY 2021 dividend increased to $2.87 (intended annualised dividend increase of $0.10) $bn 12.1 Net debt end 2020 Net debt: $24,322m; EBITDA¹: $7,586m (6.0) 1.1 CFO Net debt Capex 0.5 Deal payments and receipts² 3.9 Dividend 0.4 Other 12.1 Net debt end 2021 ex aqusition 12.3 Acquisition related³ Net debt/EBITDA: 3.2x Net debt/EBITDA adjusted for Alexion inventory fair value uplift4: 2.5x 24.3 Net debt end 2021 ● ● ● ● Capital allocation priorities Strong investment grade credit rating Reinvestment in the business Value-enhancing business development Progressive dividend policy5 1. Earnings before interest, tax, depreciation and amortisation 2. Comprises purchase and disposal of intangible assets, payment of contingent consideration from business combinations, purchase and disposal of non-current asset investments, movement in profit participation liability and disposal of investments in associates and joint ventures 3. Comprises for Alexion acquisition: Upfront payment of ($13,349m), payments upon vesting of employee share awards ($211m) and movement in net debt related to acquisitions +$1,307m. AstraZeneca credit ratings: Moody's: short-term rating P-2, long-term rating A3, outlook negative. S&P Global Ratings: short-term rating A-2, long-term rating A-, 15 CreditWatch neutral. 4. EBITDA adding back the impact of $2,198m (FY 2020: $nil) unwind of inventory fair value uplift recognised on acquisition of Alexion 5. Progressive dividend policy defined as either stable or increasing dividend per share in US dollar terms. &#163 Oncology Dave Fredrickson EVP Oncology Business Susan Galbraith EVP Oncology R&D#17Tagrisso and Imfinzi Increased reimbursement and launches offsetting COVID-19 impact on diagnosis Tagrisso: 13% growth to $5.0bn Approvals/Reimbursements: 69/19 (adjuvant), 92/52 (1L), 92/68 (2L) $m 1,400 1,200 1,000 800 600 400 200 0 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 2019 2020 US Europe EROW EM 2021 • US +14% FLAURA and ADAURA new patient starts and DoT growth 2021 exit diagnosis rates for lung 10-15% below pre-pandemic levels ● Europe +25% (Q4 +7%) Increased reimbursement EROW +14% Japan +8% • EM +6% (Q4 +23%) China 1st-line volume growth continues after NRDL implementation $m 700 600 500 400 300 200 100 Imfinzi: 16% growth to $2.4bn Approvals/Reimbursements: 75/35 (NSCLC), 67/9 (ES-SCLC) Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 2019 2020 US Europe EROW EM 2021 • US +5% (Q4 +10%) ● Europe +25% Growth from PACIFIC and CASPIAN launches • EROW +23% Improving CRT rates and strong CASPIAN demand driving growth despite mandatory price adjustment in Japan in August • EM +68% (Q4 +44%) Strong underlying demand China destocking in Q4 2021 17 EROW= established rest of world; EM = emerging markets; 1L = first line; 2L = second line; DoT= duration of treatment; ES-SCLC = extensive-stage small cell lung cancer; CRT = chemoradiation therapy; NRDL = national reimbursement drug list. B#18Lynparza The globally leading PARP inhibitor across four tumour types $m 700 600 500 400 300 200 100 0 Q4 2019 Product sales 30% growth to $2.3bn Q1 Q2 2020 US Europe EROW EM Q3 Q4 Q1 Q2 2021 Q3 Q4 Growth in all regions Approvals: 86 (OC), 84 (mBC), 70 (mCRPC) ● ● ● ● US +24% Growth driven by ovarian, prostate and breast performance 2021 exit diagnosis rates: 5-15% below baseline Europe +35% Increasing HRD testing, launches in new markets EROW +28% Japan +21% driven by PAOLA-1 launch EM +41% Strong demand growth across EM, offsetting China NRDL renewal impact Collaboration revenue¹ $3.5bn recorded, $4.2bn future potential $m 1,000 900 800 700 600 500 400 300 200 100 0 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 2018 2017 2019 Upfront payment Option payments Regulatory milestones Sales milestones || 18 PARP = poly ADP-ribose polymerase; OC = ovarian cancer; mBC = metastatic breast cancer; mCRPC = metastatic castration resistant prostate cancer; HRD = homologous recombination deficiency. 1. at actual exchange rates. Lynparza is being developed and commercialised in collaboration with Merck & Co., Inc., Kenilworth, NJ, US, known as MSD outside the US and Canada. 2020 2021#19Calquence and Enhertu Strong launch trajectories continue $m 450 400 350 300 250 200 150 100 50 0 Calquence: 136% growth to $1.2bn Approvals/Reimbursements: 76/25 (CLL), 37/13 (MCL) Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 2019 2020 US Europe EROW EM 2021 • Global $1,238m; US $1,089m • ● US CLL Strong performance with 54% share of new patients starts Global CLL Continued launch performance in DE, UK, FR and International markets • US MCL Preferred BTKI in relapsed refractory MCL CALQUENCE calenutrits caps 100 mg $m 80 70 60 50 40 30 20 10 Enhertu: 123% growth to $214m Approvals/Reimbursements: 9/4 (mBC), 4/2 (GC) Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 2019 US Europe EROW EM 2020 2021 ● ● ● ● Global $214m; US $169m Total in-market sales ex-Japan: $426m US #1 in 3rd-line HER2+ mBC, continuing launch in 2nd-line GC, NCCN and ESMO guidelines for 2nd-line mBC Global Strong launches in France and UK 19 CLL chronic lymphocytic leukaemia; MCL = mantle cell lymphoma; BTKI = Bruton tyrosine kinase inhibitor; GC = gastric cancer; 3L = 3rd-line; NCCN = National Comprehensive Cancer Network; ESMO = European Society for Medical Oncology. C ENHERTU (lam rasturnab denotecan-mok) For Injection 100 mg per vial Only For inge P T KEEP REFRIGERATED Perry www. de Daichi Sankyo AdtraZeneca#20Oncology: R&D pipeline highlights Strong congress presence; HIMALAYA and TOPAZ-1 support launch into GI cancers • TROPION-PanTumor01: promising ● evidence of the anti-tumour activity of datopotamab deruxtecan in TNBC¹ Antitumor Responses by BICR Patients with TNBC without prior Topo I inhibitor-based ADC Best Percent Change in SoD From Baseline by BICR (n=26) 100 80- 60- 40 -20 -40 SABCS Enhertu, Dato-DXd, Lynparza, Imfinzi and camizestrant -60 - -80 -100 Dose level 8 mg/kg 6 mg/kg Patients, n (%)³ ORR CR/PR (confirmed) CR/PR (pending confirmation) Non-CR/non-PD Stable disease Not evaluable Disease control rate PD SG/DXd Naïve Patients with Measurable Disease at BL (n=27) 14 (52) 13 (48) 1 (4) 0 9 (33) 1 (4) 22 (81) 4 (15) Median follow-up: 8.8 months (range, 4-13 months) • ASCEND: durable efficacy for Calquence over three years in r/r CLL² Progression-Free Survival (%) 100++ 80- 60- 40- 20- 0- ASH Calquence and capivasertib Acalabrutinib vs IdR vs BR Acalabrutinib:ldR HR (95% CI): 0.31 (0.22, 0.43) P<0.0001⁰ Acalabrutinib:BR HR (95% CI): 0.25 (0.16, 0.40) P<0.0001 Acalabrutinib IdR BR 9 10 11 12 13 14 15 16 17 18 19 20 21 Months Median PFS: NR 63% Median PFS: 16.2 mo Median PFS: 18.6 mo 33 34 35 36 37 38 39 40 41 42 No. at risk Acalabrutinib 155 154 153 151 148 147 143 142 142 139 138 137 133 131 129 128 127 12 IR 110116116114113112106 00 00 00 82 81 73 72 66 57 56 52 40 40 40 48 45 41 40 37 35 35 32 32 29 28 27 27 BR 36 34 34 33 33 33 32 30 29 28 27 26 22 22 20 19 18 17 17 16 14 14 13 12 12 10 8 8 7 7 6 6 5 5 4 3 2 2 1 0 • Positive results in IO: HIMALAYA (HCC) and TOPAZ-1 (BTC) Enhertu gastric and colorectal trials³ ● DESTINY-CRC01 Best Percentage Change in Tumor Size in Cohort A Best Percentage Change From Baseline in the Sum of Diameters of Measurable Tumors 20 -40 -60 ASCO GI Imfinzi, tremelimumab and Enhertu -80 -100 HER2 IHC 3+ or IHC 2+/ISH+ Cohort A (n = 49³) IHC 3+ IHC 2+/ISH+ Prior anti-HER2 treatment HER2 IHC 2+/ISH+ with an NRAS mutation Wealth of new data reinforces leadership in Oncology, underscoring ambition to redefine cancer care 20 SABCS = San Antonio Breast Cancer Symposium; TNBC = triple negative breast cancer; ASH = American Society of Hematology; ASCO GI American Society of Clinical Oncology Gastrointestinal Cancers Symposium 1. Krop et al, SABCS 2021, Presentation number GS1-05. 2. Jurczak et al, ASH 2021 Presentation abstract number 393. 3. Yamaguchi et al, ASCO GI Presentation abstract number 242.#214 BioPharmaceuticals, Emerging Markets Ruud Dobber EVP, BioPharmaceuticals Business Mene Pangalos EVP, BioPharmaceuticals R&D 3#22BioPharmaceuticals: Cardiovascular, Renal and Metabolism Total Revenue $8.0bn; growth +9% Farxiga: 49% growth to $3.0bn Strong momentum continues, fastest growing SGLT2i globally 22 $m 900 800 700 600 500 400 300 200 100 0 Q4 2019 Q1 Q2 Q3 Q4 2020 US Europe EROW EM Q1 Q2 Q3 Q4 2021 US +29%, Europe +52% and EM +70%, boosted by HFrEF and CKD launches • Volumes growing faster than the SGLT2i market in most major markets China NRDL status renewed • #1 innovative anti-diabetic in China and Brazil Now blockbuster status in EM US branded K+ binder TRX share¹ ● 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Jul-19 Lokelma Global sales of $175m Sep-19 Jan-20 Nov-19 Mar-20 May-20 Jul-20 Sep-20 Nov-20 SGLT2i = sodium-glucose transport protein 2 inhibitor; HFrEF = heart failure with reduced ejection fraction; CKD = chronic kidney disease; K+ = potassium; TRx = total prescriptions. 1. IQVIA US monthly total prescription share data Jan-21 Mar-21 Jul-21 May-21 Sep-21 Nov-21 Lokelma Branded competitor Continued strong growth in US and Japan. Expanding in new markets in Europe with new reimbursements achieved China NRDL listing from January 2022 61%#23BioPharmaceuticals: Respiratory and Immunology Total Revenue $6.0bn; growth +9% $m 400 300 200 100 ● 0 ● Q4 2019 Fasenra 31% growth to $1.3bn Q1 Q2 Q3 Q4 Q1 US Europe EROW EM 2020 Q2 Q3 Q4 Leading biologic in eosinophilic asthma¹ • Global performance driven by new patient share Now a blockbuster medicine 2021 Fasen 730 mg/ml Breztri COPD launch progressing; sales of $203m T8 triple FDCs brand share (DOT)² 4% 13% Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Global launch underway with 13% triple FDC branded market share in T8 countries, with 23% share in US, CN, JP Demand sales volume increase in China following NRDL inclusion Saphnelo SLE launch progressing • Positive early market response, despite COVID-19 headwinds US: $8m sales, with 35% NBRx share of i.v. market³ Japan: formulary listing submissions are proceeding EU CHMP positive opinion 23 1. Based on IQVIA MIDAS consolidated total patient top-7 market share (markets: US, JP, DE, FR, ES, IT, UK) in Q3 2021. 2. IQVIA MIDAS monthly days of therapy month end November 2021. 3. IQVIA LAAD claims data. NBRX = new to brand prescriptions; COPD = chronic obstructive pulmonary disorder; FDC = fixed dose combinations; i.v. = intravenous. NDC 0310-3040-00 Saphnelo (anifrolumab-fnia) Injection Rx only 300 mg/2 mL (150 mg/mL) For Intravenous Infusion After Dilution Must dilute before use. See prescribing information. Single-dose vial Discard unused portion Store refrigerated at 2°C to 8°C (36°F to 46°F). Ceep vial in original carton to protect from light. Jo not shake or freeze. aphnel tion 300 single-dose vial Ma only AstraZeneca 4#24Tezspire approved for severe asthma in the US First and only biologic approved with no phenotype or biomarker limitation Addressing the unmet need in severe asthma c.2.5m of patients eligible for biologic treatment¹ c.83% patients not currently treated with biologics² Indicator Tezspire addresses the full spectrum of severe asthma patients Blood eosinophils (≥ 300 cells/μL) Blood eosinophils (<300 cells/μL) Blood eosinophils (<150 cells/μL) With allergic features Inflammatory drivers overlap % Total Patient Population ³-12 40-50% 50-60% 25-30% c.65% c. 60% TEZSPIRE™ (tezepelumab) Injection Subcutaneous Only biologic proven to significantly reduce exacerbations in these patient populations ¹AstraZeneca Data on File ²AstraZeneca Data on File; 3 Hanania NA, et al. Ann Intern Med. 2011;154 (9): 573-82, 4Yancey SW, et al. Respir Med. 2019; 151: 139-141. 5 FitzGerald JM, et al. Lancet Respir Med. 2017; 6 (1): 51-64. "Castro M, et al. N Engl J Med. 2018; 378 (26): 2486-2496.7 Wang E, et al. Chest. 2020; 157 (4): 790-804. Denton E, et al. J Allergy Clin Immunol Pract. 2021;9 (7): 2680-2688.e7. doi: 10.1016/j.jaip.2021.02.059. Epub 2021 Mar 18. Erratum in: J Allergy Clin Immunol Pract. 2021; 9 (11): 4182. PMID: 33744476. Tran TN, et al. Ann Allergy Asthma Immunol. 2016; 116: 37- 42. 10 Amaral et al. Clin Trans Allergy. 2018; 8: 13. 1¹AstraZeneca Data on file. ¹2Ding B, et al. Eur Respir J 2021; 58: Suppl. 65, OA4214. Tezspire is being developed and commercialised in collaboration with Amgen. US launch January 2022 | Regulatory submissions underway in EU and Japan#25Emerging Markets Total revenue $12.3bn (including Vaxzevria¹ revenue) Emerging markets +10%² China +4%; Ex-China EMs +21%² $m 4,000 3,500 3,000 2,500 2,000 1,500 1,000 500 Q4 2019 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 2020 China Ex-China EMS COVID-19 vaccine sales 2021 ● ● Diversified growth across geographies Launches in ex-China Emerging Markets progressing well Oncology $3.2bn, +6%: Tagrisso $1.3bn, up 6% continued impact from NRDL inclusion in China, offset by solid growth ex-China for Lynparza, Imfinzi, and Tagrisso CVRM $3.8bn, +12%: continued strong growth for Forxiga ($1.2bn, +70%) driven by HF and CKD launches Respiratory & Immunology $1.7bn, +4%: Pulmicort ($770m, -9%) due to VBP inclusion in October. Symbicort growth ($609m, +4%) mainly driven by ex-China 25 1. Vaxzevria Total Revenue' also includes Collaboration Revenue from sub-licensees that produce and supply the AstraZeneca COVID-19 Vaccine under their own trademarks. 2. Growth number calculated excluding revenue of the Vaxzevria. Growth including Vaxzevria is as follows: Emerging Market total revenue growth +36%, China +4%; Other EMs +89%. 3#26BioPharmaceuticals: R&D pipeline highlights Four NMEs approved in 2021: Saphnelo, Tezspire, Evusheld and Vaxzevria Evusheld Only long-acting antibody combination shown to prevent and treat COVID-19 • Authorised in eight countries, including US EUA Retains neutralising activity against Omicron¹ US agreements for 1.2m doses Agreements include US Gov development funding EVUSHELD ATTENTION HEALEY Vaxzevria Clinical and real-world evidence supports use as booster • 2.5bn doses supplied in 2021² Boosts immune response against Omicron³ • Retains neutralising activity after two-doses4 • Vaxzevria and AZD2816- generated similar immune response to variants of concern5 Vaxzevria 5 ml suspension for injection COVID-19 Vaccine (ChAdOx1-5 recombinant) Intramuscular use 10 multidose vials (10 doses per vial-0.5 ml per dose) 108. Comme Bang super - 179 sin bas quase) eplontersen ATTR Collaboration with lonis Pharmaceuticals • ATTR: misfolded protein and accumulation as amyloid fibrils ATTR-CM (cardiomyopathy) hATTR-PN (polyneuropathy, hereditary) Phase III trials: CARDIO-TTRansform (data 2023+) NEURO-TTRansform (data H2 2022) 26 1. Nature: doi.org/10.1038/s41586-021-04386-2 2. Includes doses shipped by sub-licensees. AstraZeneca invoiced supply is 963 million doses. 3. UK Health Security Agency: doi.org/10.1101/2021.12.14.21267615 4. The Lancet: doi.org/10.1016/S0140-6736(22)00094-0 5. Interim results from the D7220C00001 clinical trial. ATTR = transthyretin amyloidosis.#275 Rare Disease Marc Dunoyer Chief Executive Officer, Alexion 100#28Rare Disease Total Revenue $3.1bn; +9% pro rata¹ FY 2021 Growth across all regions Pro rata growth, 2021¹ 2,000 1,800 1,600 1,400 1,200 1,000 800 600 400 200 +8% +9% hi.. +11% +18% US FY 2020² FY 2021 EU EROW EM 3,500 3,000 2,500 2,000 1,500 1,000 500 0 Rare Disease performance C5 Franchise (Soliris + Ultomiris) +11% Q4; +8% pro rata FY 2021²; +11% +9%¹ Q4 2020² Q4 2021 FY 2020² FY 2021 • Soliris: double-digit volume growth in Neurology; Q4 benefitted from tender market order timing Soliris Ultomiris Strensiq Kanuma Andexxa • Ultomiris: continued conversion in PNH, aHUS despite COVID-19 impact; 14 new country launches in FY 2021 ● Strensiq: growth driven by increased demand in US • Kanuma: strong revenue growth driven by ex-US demand • Andexxa: strong revenue growth in EU, offset by COVID-related hospital access challenges in the US Opportunity for geographic expansion leveraging AstraZeneca's footprint 28 1. FY 2021 revenues from date of acquisition closing, 21 July 2021 through 31 December 2021; pro forma growth rates calculated by comparison post-acquisition revenues with the corresponding prior year revenues adjusted pro- rata to match the post-acquisition period. 2. Inclusive of total revenues previously reported by Alexion and not adjusted for consistency with AstraZeneca's accounting policies, not audited and not included in AstraZeneca's FY 2021 results.#29Expanding beyond heart failure in amyloidosis Cohesive commercial and development strategy across Cardiovascular and Rare Disease Leveraging strengths and expertise across Cardiovascular, Rare Disease OF OF Farxiga in Heart Failure (HFrEF, HFPEF) OF F Ex. ATTR-CM ~400-500k patients WW¹,2 ● Amyloidosis commonly misdiagnosed as HFpEF TTR and AL represent majority of amyloidosis diagnoses ATTR amyloidosis AL amyloidosis ~20k patients US, EU5³ Complementary MOAs needed in ATTR to address full spectrum of patient need ATTR-CM NYHA Patient Severity¹ NYHA I less severe STABILISER SILENCER DEPLETER NYHA II ALXN2060 acoramidis (BridgeBio) eplontersen (lonis) NYHA III 29 1. Mohamed-Salem L et al. Int J Cardiol. 2018 Nov 1; 270:192-196. doi: 10.1016/j.ijcard. 2018.06.006 2. Cucaden C, et al. J Nucl Cardiol. 2020 May 8 3. Quock, T. P., et al. Blood Adv. 2018; 2(10):1046-1053; Internal epidemiological analysis: Mayo Stage Illa + b 4. New York Heart Association (NYHA) Functional Classification. MoA = mechanism of acton. NYHA IV more severe NI006 (Neurimmune) Building a strategic presence in amyloidosis#30Investing in Rare Disease Late-stage weighted pipeline, multiple long-term growth opportunities 30 Complement Beyond Complement ULTOMIRIS (2nd Generation C5) SOLIRIS ALXN2040 (Factor D) ALXN2050 (Factor D) Robust late-stage pipeline breadth of LCM and NME opportunities ALXN1720 (3rd Generation CS) ALXN1820 (Anti-Properdin) ALXN1840 ALXN2060 CAEL-101 ALXN1850 N1006 SC Weekly IV (gMG) IV (NMOSD) IV (HSCT-TMA) IV (CM-TMA) IV (DM) IV (LN/IGAN) IV (GBS) Japan Only Oral (PNH with EVH) Oral (Geographic Atrophy) Oral (PNH Monotherapy) Oral (gMG) Oral (LN/IgAN) SC SC HV Study Oral (Wilson) Oral (ATTR-CM) Japan Only IV (AL Amyloidosis) SC (HPP) IV (ATTR-CM) PHASE 1 PHASE 2 FDA = Food and Drug Administration; PDUFA = Prescription Drug User Fee Act. PHASE 3 Diversified pipeline with multiple late-stage programmes beyond complement Expanding & diversifying our Rare Disease portfolio; key events in Q4 • US FDA accepted Ultomiris in generalised myasthenia gravis for priority review, PDUFA date in Q2 2022 Exclusive global license for N1006, novel depleter in development for ATTR amyloidosis Investing in complement capabilities with expansion of New Haven research facility, and establishment of European development hub in Barcelona. B#316 Closing remarks and Q&A 00 3262#32Pipeline catalysts for 2022 - 2023 Industry leading news flow ww Regulatory decision Regulatory submission and/or acceptance Key Phase III data readouts H1 2022 Lynparza - breast cancer (adjuvant) (US) Enhertu - HER2+ breast cancer (2L) (US) Brilique - stroke (THALES) (CN) Forxiga - chronic kidney disease (CN) Fasenra-nasal polyps (US) Saphnelo - lupus (SLE) (EU) tezepelumab - asthma (EU, JP) Ultomiris-gMG (US) Imfinzi +/- tremelimumab - liver cancer (1L) (HIMALAYA) Imfinzi - biliary tract cancer (TOPAZ-1) Lynparza - prostate cancer (1L) (US, JP) Enhertu - HER2-low breast cancer (3L) (DESTINY- Breast04) PT027-asthma (US) Vaxzevria-COVID-19 (US) Evusheld-COVID-19 outpatient treatment (EU, JP) nirsevimab - respiratory syncytial virus Ultomiris - subcutaneous, PNH and aHUS (EU) Imfinzi - NSCLC (1L) (PEARL) Imfinzi - cervical cancer (CALLA) Imfinzi - NSCLC (unresectable Stg. III) (PACIFIC-2) Enhertu - HER2-low breast cancer (3L) (DESTINY- Breast04) Farxiga - HFPEF (DELIVER) Ultomiris - NMOSD H2 2022 Tagrisso - EGFRm NSCLC (adjuvant) (JP) Imfinzi +/- tremelimumab - NSCLC (1L) Lynparza - ovarian cancer (1L) (CN) Lynparza - prostate cancer (1L) (EU) Lynparza - breast cancer (adjuvant) (EU, JP) Enhertu - HER2+ breast cancer (2L) (EU, JP) Enhertu - HER2+ gastric cancer (2L) (EU) Koselugo - NF1-PN (JP) Ultomiris-gMG (EU, JP) Ultomiris - subcutaneous, PNH and aHUS (US) Imfinzi - NSCLC (unresectable, Stg. III) (PACIFIC-2) Imfinzi - NSCLC (1L) (PEARL) Imfinzi - cervical cancer (CALLA) Imfinzi - liver cancer (locoregional) (EMERALD-1) Enhertu - HER2+ breast cancer (3L) (DESTINY-Breast02) Calquence - CLL (ELEVATE-TN) (JP) Koselugo - NF1-PN (SPRINT) (CN) Farxiga - HFpEF (DELIVER) eplontersen – hATTR-PN (NEURO-TTRansform) Ultomiris-NMOSD ALXN1840-Wilson disease Imfinzi - SCLC (limited-stage) (ADRIATIC) Imfinzi - liver cancer (locoregional) (EMERALD-1) Enhertu - HER2+ breast cancer (3L) (DESTINY-Breast02) Calquence - MCL (1L) (ECHO) eplontersen – hATTR-PN (NEURO-TTRansform) Fasenra-HES (NATRON) Fasenra- EOE (MESSINA) acoramidis - ATTR-CM (JP) Tagrisso - EGFRm NSCLC (1L) (FLAURA2) Tagrisso - EGFRm NSCLC (unresectable Stg. III) (LAURA) Imfinzi - limited-stage SCLC (ADRIATIC) Imfinzi- bladder cancer (1L) (NILE) Imfinzi - bladder cancer (muscle invasive) (NIAGARA) Imfinzi - liver cancer (adjuvant) (EMERALD-2) Imfinzi - NSCLC (neoadjuvant) (AEGEAN) Lynparza - breast cancer (adjuvant) (CN) Lynparza - colorectal cancer (1L) (LYNK-003) capivasertib - TNBC (locally adv./met.) (CAPItello-290) capivasertib - HR+/HER2-neg. breast cancer (CAPItello-291) Dato-DXd - NSCLC (3L) (TROPION-Lung01) Tagrisso - EGFRm NSCLC (1L) (FLAURA2) Tagrisso - EGFRm NSCLC (unresectable Stg. III) (LAURA) Imfinzi- bladder cancer (muscle invasive) (NIAGARA) Imfinzi - NSCLC (neoadjuvant) (AEGEAN) Imfinzi - liver cancer (adjuvant) (EMERALD-2) Imfinzi - bladder cancer (1L) (NILE) 2023 Lynparza - colorectal cancer (1L) (LYNK-003) Lynparza + Imfinzi - ovarian cancer (1L) (DUO-O) Lynparza + Imfinzi- endometrial cancer (1L) (DuO-E) Enhertu - HER2oe gastric cancer (DESTINY-Gastric03) Enhertu - HER2m NSCLC (unresectable) (DESTINY-Lung02) Enhertu - HER2-low breast cancer (2L) (DESTINY-Breast06) EGFRm = epidermal growth factor receptor mutated; HER2-low = human epidermal growth factor receptor 2 low; Stg. = stage; HFpEF = heart failure with preserved ejection faction; NMOSD = neuromyelitis optica spectrum disorder; MCL = mantle cell lymphoma; HES = hyper eosinophilic syndrome; EOE = eosinophilic oesophagitis; TNBC = triple negative breast cancer; adv = advanced; met = metastatic; HR+ = 32 hormone receptor positive; HER2-neg = human epidermal growth factor receptor 2 low; HER2oe human epidermal growth factor receptor over expressing; HER2m = human epidermal growth factor mutant; CRwNP = chronic rhinosinusitis with nasal polyps; EGPA= eosinophilic granulomatosis with polyangiitis. Oncology BioPharmaceuticals Rare Disease Fasenra- EOE (MESSINA) Fasenra- EGPA (MANDARA) Fasenra-HES (NATRON) Fasenra - severe asthma (CN) (MIRACLE) acoramidis - ATTR-CM (JP) danicopan - PNH with extravascular haemolysis Calquence - CLL (1L) (AC-CL-311) capivasertib - TNBC (locally adv/met) (CAPItello-290) capivasertib - HR+ HER2-neg breast cancer (1L) (CAPItello-291) camizestrant - HR+ HER2-neg breast cancer (SERENA-6) Dato-DXd - NSCLC (3L) (TROPION-Lung01) Farxiga - myocardial infarction (DAPA-MI) roxadustat - anaemia of myelodysplastic syndrome Fasenra - severe asthma (MIRACLE) Fasenra - CRwNP (ORCHID) Fasenra- EGPA (MANDARA) Fasenra - bullous pemphigoid (FJORD) Soliris - guillain-barre syndrome (JP) danicopan - PNH with extravascular haemolysis#3333 AstraZeneca PADA AstraZeneca: the next chapter Industry-leading growth, best-in-class innovative pipeline Double-digit CAGR through 2025 |DGO Longer-term growth fueled by existing portfolio and new innovative medicines Differentiated, durable portfolio Attractive LOE profile, unrivalled R&D productivity and pipeline Financial execution % Continued focus on operating leverage and cash generation Reinvestment in our main disease areas High-growth pipeline opportunities, value-enhancing business development B#34Q&A Full-year and Q4 2021 Results 34 Pascal Soriot Executive Director and Chief Executive Officer Dave Fredrickson Executive Vice President, Oncology Business Ruud Dobber Executive Vice President, BioPharmaceuticals Business Marc Dunoyer Chief Executive Officer, Alexion Aradhana Sarin Executive Director and Chief Financial Officer Susan Galbraith Executive Vice President, Oncology R&D Mene Pangalos Executive Vice President, BioPharmaceuticals R&D Leon Wang Executive Vice President, International 3#35A Appendix 12#36Scope 1+2 emissions reduction targets Thousand tonnes tCO₂e Absolute Scope 1+2 emissions reduction targets 1,600 1,400 1,200 1,000 800 600 400 200 O AstraZeneca 2015 2020 Sanofi GSK Novartis¹ Novo Nordisk 2025 Pfizer Merck & Co Johnson & Johnson 2030 Biogen AbbVie 2035 Takeda 2040 2045 Roche 2050 Company AstraZeneca Novo Nordisk Takeda Sanofi Merck & Co Roche Johnson & Johnson GSK Biogen Bayer Pfizer AbbVie Target ranking Target temperature alignment (°C) ² Lonza Source: Pollination, using Company reports, CDP. Note: Target trajectory is plotted from base year to target year. Actual historical emissions profiles from 2015-2020 will differ. Bayer's target is not displayed due to scale of chart. Lonza's target is not displayed due to being an intensity target. 1. Novartis' target is to be carbon neutral across Scope 1+2 by 2025 from 2016 base year, level of mitigation targeted is unknown. 2. Utilising the SBTi temperature 36 rating methodology. * For AstraZeneca Pollination graphed the SBT "reduce absolute scope 1 and 2 GHG emissions 98% by FY2026 from a FY2015 base year" <1.1 <1.1 <1.1 1.15 1.15 1.24 1.37 1.38 1.39 1.40 1.40 1.64 2.52 Rank 1 2 3 4 5 6 7 8 9 10 11 12 13#37Early pipeline news flow (1/2) Next key milestone by project Oncology Project 37 adavosertib ceralasertib oleclumab MEDI5752 AZD5991 AZD0466 AZD8205 AZD5305 AZD0171+ Imfinzi AZD7789 AZD2936 AZD4573 Target WEE1 ATR CD73 PD-1/ CTLA4 MCL1 Bcl-2/xL B7H4 ADC PARP1 sel anti-LIF mAb + PD-L1 PD-1/TIM3 PD-1/TIGIT CDK9 Phase || || || 1/11 트 1/11 || 1/11 1/11 = 1/11 1 || Indication uterine, pancreatic cancer solid tumours blood cancers solid tumours solid tumours blood cancers blood cancers solid tumours solid tumours NSCLC NSCLC NSCLC blood cancers Next milestone Phase III start Phase II data, 2023+ Phase II data, 2023 Phase I/II data, 2023+ Phase I/II data, 2023+ Phase II data, 2023+ Phase I/II data, 2023+ Phase I/II data, 2023+ Phase II data, 2023+ Phase I/II data, 2023+ Phase I data, 2023+ Phase II data, 2023 BioPharmaceuticals: CVRM Project cotadutide cotadutide AZD4831 AZD5718 AZD9977 + Farxiga zibotentan + Farxiga AZD2693 AZD8233 tozorakimab Target GLP-1/ glucagon GLP-1/ glucagon MPO FLAP MCR + SGLT2 ETR + SGLT2 PNPLA3 PCSK9 IL-33 Phase || || II/III || || || | || || Indication NASH DKD HFpEF CKD HF with CKD CKD NASH dyslipidaemia DKD Next milestone Phase III start, H2 2022 Phase II data, H1 2022 Phase II/III data, 2023+ Phase II data, 2023 Phase II data, 2023 Phase II data, H2 2022 Phase I data, H1 2022 Phase II data, H2 2022 Phase II data, 2023 B#38Early pipeline news flow (2/2) Next key milestone by project BioPharmaceuticals: Respiratory and Immunology 38 Project tozorakimab tozorakimab tozorakimab tozorakimab AZD1402 AZD4604 MEDI7352 MEDI7352 Target IL-33 IL-33 IL-33 IL-33 IL-4R alpha inhaled JAK NGF TNF NGF TNF Phase || || || || 11 1 || || Indication asthma COPD AD COVID-19 asthma asthma painful diabetic neuropathy osteoarthritic pain Next milestone Phase II data, H2 2022 Phase III start, 2022 Phase II data, H2 2022 Phase II data, H1 2022 Phase II data, H2 2022 Phase I data, 2023 Phase II data, 2023 Phase II data, 2023 Rare Disease Project ALXN1720 danicopan danicopan ALXN1820 ALXN2050 ALXN2050 ALXN2050 ALXN1850 Target 3rd-gen C5 Factor D Factor D anti-properdin Factor D Factor D Factor D next-gen asfotase alfa Phase I || I || || || | Indication gMG geographic atrophy PNH with EVH haematology PNH monotherapy gMG renal indications hypophosphatasia Next milestone Phase I data, H1 2022 Phase II data, 2023+ Phase III data, 2023 Phase I data, 2023 Phase II data, H1 2022 Phase II data, H1 2022 Phase II data, 2023+ Phase I data, H2 2022 B#3939 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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