AstraZeneca : Opening session and Q&A presentation

Q&A

Chronic diseases are a staggering, growing burden to patients and society

Chronic

T2 DiabetesHeart FailureKidney DiseaseAsthmaCOPDLupus1

The ambition is to transform treatment for billions of people living with chronic diseases

1. Systemic lupus erythematosus, Cutaneous lupus, lupus nephritis 2. Ogurtsova K, et al. Diabetes Res Clin Pract. 2017;128:40-50 3. Global Burden of Disease Study 2016. Lancet. 2017;390:1211-1259 4. Jager, et al. Nephrology Dialysis Transplantation 2019;34:1803-1805 5. GINA, The Global Asthma Report 2018 6. Adeloye D, et al. J Glob Health. 2015;5(2):020415 7. Lupus Foundation of America. Lupus facts and statistics [Online]. 709-33 8. WHO. Diabetes [online] 9. Mozaffarian D, et al. Heart Disease and Stroke Statistics-2016 Update: A Report From the American Heart Association. Circulation.

4 2016;133(4):e38-360 10. Carney EF. Nature. 2020:16;251 11. Global Asthma Report. 2014 [online] 12. The Guardian. 2012 [online] 13. Yen EY, Singh RR. Arthritis Rheumatol. 2018; 70(8):1251-55. 13.

Leading with an unmatched portfolio and growing pipeline

Unmatched portfolio

CVRM1

Roxadustat Capsules

R&I2

New CVRM and R&I today

Portfolio tomorrow

12,000

10,000

+24%

8,000

6,000

4,000

2,000

2017

2018

2019

2020

Phase III LCM

Phase III NME

Farxiga DAPA-CKD

SGLT2

CKD

roxadustat6

HIF-PH anaemia of CKD, MDS

Farxiga DAPA-MI

SGLT2 prevention of HF and CV death following a MI3

PT0277 ICS/SABA asthma

Farxiga DELIVER

SGLT2 HFpEF4

anifrolumab TULIP Type I IFN receptor

SLE

Fasenra EDD5 diseases

tezepelumab8

TSLP severe asthma

Fasenra

IL5R COPD

nirsevimab9 mAb-YTE passive RSV immunisation

Breztri LABA/LAMA/ICS asthma

brazikumab

IL23

Crohn's disease

US Europe Established Rest of World (ERoW) Emerging markets (EM)

1. Cardiovascular, Renal & Metabolism 2. Respiratory & Immunology.

Product Sales at actual exchange rates. Growth rate at CER.

3. Acute myocardial infarction 4. Heart failure with preserved ejection fraction 5. Eosinophilic driven diseases including: eosinophilic granulomatosis with polyangiitis, eosinophilic esophagitis, hypereosinophilic syndrome, nasal polyps, bullous pemphigoid 6. Collaboration with FibroGen Inc. 7. Collaboration with Avillion LLP. 8. Collaboration with Amgen Inc. 9. Collaboration with Sanofi S.A.

Strong commercial execution

T2D1 and HF2

2,000

1,500

1,000

500

0 2017

2018

2019

2020

CKD3 under review

US Europe ERoW EM

Severe asthma

1,000

800

600

400

200

0 2018

2019

2020

A leading biologic medicine4

Hyperkalaemia

100

0 2019

2020

Accelerated momentum

Product Sales at actual exchange rates. 1. Type-2 diabetes 2. Heart failure 3. Chronic kidney disease 4. Leading novel biologic medicine in severe asthma in many markets based on new to brand prescriptions. Market shares are total patient share in severe, uncontrolled asthma; specialty pharmacies and 'buy and bill' market, IQVIA market research.

Anaemia of CKD

Roxadustat Capsules

H1 2020

H2 2020

Strong start in China

Total revenue booked by AstraZeneca. Collaboration with FibroGen Inc. which booked in-market sales ($72.5m) in China in 2020.

Footprint across four continents and over 70 countries

Source: The World Bank,https://data.worldbank.org/indicator/SH.XPD.CHEX.GD.ZS.

Strong growth both in China and other EMs

China

+68%

Growth in New CVRM and R&I product sales

EMs ex. China

+56%

Growth in New CVRM and R&I product sales

EMs ex. China: Forxiga

Ranked #1

Farxiga is ranked as the number one SGLT2 inhibitor in nine EM ex. China countries

Product sales at actual exchange rates. Growth rates at CER.

Unique opportunity to transform kidney care by 2025

Underdiagnosed and undertreated

>2 billion

People at risk of developing CKD1

c.840 million

Estimated people with CKD2

+12%

Actual people diagnosed with CKD3

Expanding early diagnosis and care

Three thousand

Hospitals participating

800 thousand

Patients screened to date

50%

Vivekanand Jha, Carmine Zoccali, A single number for advocacy and communication - worldwide more than 850 million individuals have kidney diseases, Nephrology Dialysis Transplantation, Volume 34, Issue 11, November 2019, Pages 1803-1805,https://doi.org/10.1093/ndt/gfz1743. Vaidya SR, Aeddula NR. Chronic Renal Failure 2019. Available at: https://knowledge.statpearls.com/chapter/0/28357 (Accessed Oct 2020).

Transforming CKD management

Will increase treatment at Stage 3 by 2025

Partnerships

THE PRESSURE ISON TO DIAGNOSE

CHRONIC KIDNEY DISEASE (CKD)

AS FEW AS 10% OF ADULTS WITH CKD ARE DIAGNOSED, EVEN IN STAGE 31,2

TAKE THE PRESSURE OFF BY FOLLOWING THESE THREE SIM PLE STEPS:

SEE WHY THE PRESSURE IS ON TO

HIGH PREVALENCE LOW DIAGNOSIS

DIAGNOSECKD IN ITSEARLIER

STAGES

CKD is a life-threatening disease that is vastly underdiagnosed.3

CKD affects an estimated 1 in 7

American adults.4

Only 1 in 10 American adults with Stage 3 CKD are diagnosed.1

Learn more about the importance of diagnosing CKD early.

GET THE CKD GUIDE

N EXT: Impact of Early Intervention

CKD=chronic kidney disease; CV=cardiovascular; CVD=cardiovascular disease; eGFR=estimated glomerular filtration rate; GFR=glomerular filtration rate;

HTN=hypertension; T2D=type 2 diabetes.

References:

1. Ryan TP, Sloand JA, Winters PC, Corsetti JP, Fisher SG. Chronic kidney disease prevalence and rate of diagnosis. Am JMed. 2007;120(11):981-986.
2. Ravera M, Noberasco G, Weiss U, et al. CKD awareness and blood pressure control in the primary care hypertensive population. Am JKidney Dis.
2011;57(1):71-77.
3. Chronic kidney disease basics. Centers for Disease Control and Prevention. Page reviewed February 7, 2020. Accessed February 9, 2021.https://www.cdc.gov/kidneydisease/basics.html
4. Kidney Disease: The Basics. National Kidney Foundation. Published May 2020. Accessed February 9, 2021.https://www.kidney.org/news/newsroom/factsheets/KidneyDiseaseBasics
5. Alabama Department of Public Health. Special Task Force on Chronic Kidney Disease report. April 2007. Accessed February 9, 2021.https://www.alabamapublichealth.gov/publications/assets/kidneydiseasereport.pdf
6. Lewis EJ, Hunsicker LG, Clarke WR, et al; Collaborative Study Group. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl JMed. 2001;345(12):851-860.

7. Go AS, Chertow GM, Fan D, McCulloch CE, Hsu C-Y. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl JMed.
2004;351(13):1296-1305.
8. Kidney disease statistics for the United States. National Institutes of Health. National Institute of Diabetes and Digestive and Kidney Diseases. December
2016. Accessed February 9, 2021.https://www.niddk.nih.gov/health-information/health-statistics/kidney-disease
9. Schnaper HW. Remnant nephron physiology and the progression of chronic kidney disease. Pediatr Nephrol. 2014;29(2):193-202.
10. Collard D, van Brussel PM, van de Velde L, et al. Estimation of intraglomerular pressure using invasive renal arterial pressure and flow velocity measurements in humans. JAm Soc Nephrol. 2020;31(8):1905-1914.

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The Burden	Impact of Early	Know Your Patients'	Who's at	How to Talk CKD	Underlying	Resources for You
of CKD	Intervention	Numbers	Ri sk ?	With Patients	Mechanism of CKD	and Your Patients

Screened patients that have elevated albumin-to-creatinine ratio (ACR)

1. Liyanage T, Ninomiya T, Jha V, Neal B, Patrice HM, Okpechi I, Zhao MH, Lv J, Garg AX, Knight J, Rodgers A, Gallagher M, Kotwal S, Cass A, Perkovic V. Worldwide access to treatment for end-stage kidney disease: a systematic review. The Lancet. 2015 May 16;385(9981):1975-82. doi: 10.1016/S0140-6736(14)61601-9. Epub 2015 Mar 13. PMID: 25777665 2. Kitty J Jager, Csaba Kovesdy, Robyn Langham, Mark Rosenberg,

Transforming care for 1m patients with severe asthma by 2030

Aiming for biologics uptake similar to other inflammatory diseases

Headroom for growth Accelerating uptake and access

34 million

Patients with severe asthma1,2

45%

treated in primary care3

15%

eligible patients receive a biologic3,4

Digital

Activation and referral tools driving specialist treatment review

10 1. GINA, The Global Asthma Report 2018 2. Wenzel S, et al. Am J Respir Crit Care Med. 2005;172:149-160 3. AstraZeneca 4. Versus 45% in rheumatoid arthritis (US).

Enabling @homemonitoring treatment

39 thousand

Patients enrolled

42%

Patients self-administer Fasenra

Building the BioPharmaceuticals team of the future

Roxadustat Capsules

Applying advanced data science techniques that enable Transfodramta tarneaalytmticesnttofionrform billions ofcopmeompelrecilaivl isntrgatwegitiehs chronic diseases

Unmatched portfolio

Agenda

Q&A

AstraZeneca's 5R framework has increased productivity

Identifying the right target

Making sure the molecule gets to the right tissue where it is neededEnsuring the right safety with minimal side effectsSelecting the right patients that will benefit

Defining the right commercial value and future viability

Embedding the right digital solutions to improve efficiency and deliver quality gains

Source: AstraZeneca based on industry benchmarks (peer companies) provided by CMR International (Clarivate).

R&D productivity in 2020

Progress made across all R&D

123	39%
250
high-impact journal1 manuscripts	increase in the number of
published in 2020 (vs. four in 2012)	Phase II projects from 2016-2020
200
890	15
150
journal publications overall in 2020	projects with validated mechanism
of action in 2016-2020
100
40	29
50
projects with regulatory	regulatory approvals in 2020
designations in 2020
0

(vs. 367 in 2012)

1. High-impact peer-reviewed journals are those with an impact factor (IF) exceeding 15 using Thomson Reuters (TR) five year IF score.

2. TR five year IF. 3. High-quality peer-reviewed journals with IF ≥5 <15 using TR five year IF score. Contains exception list considered by AstraZeneca as high quality but has IF <5. Source: Scopus retrieval (algorithm includes journal publications up to Phase III), AstraZeneca analysis.

High impact publications High quality publications2 Total publications

Focus areas to further improve productivity

Enhancing disease understanding	Broadening therapeutic platforms	Predicting clinical outcomes	Pioneering new approaches in the clinic
Data science and artificial intelligence (AI)

Identifying new targets through AI-enabled big data

Source: Groopman et al. NEJM (2019); Povysil et al. JAMA (2020); Kumar et. al. American Society of Nephrology Congress October (2020).

A broad set of therapeutic platforms to target any biology

PROTACs = proteolysis targeting chimeras, siRNA = small interfering RNA, mRNA = messenger RNA, RNA = ribonucleic acid, DNA = deoxyribonucleic acid.

Cell therapy approaches focused on regeneration ongoing across all therapy areas

Current status

PROTAC projects

Five

Projects with in vivo efficacy

Five

E3 ligases enabled for project application

Three

Projects in lead optimisation

Novel E3 ligand with

reduced safety risk

Traditional Thalidomide-likeNovel E3 ligand

E3 ligand

Hydrolysis

Racemisation

Potency

Stability Racemisation Teratogenic

260 nM T1/2<30 min

161 nM T1/2 >200 h

Yes

No No

Patent applications filed in 2020

In vivo activity of PROTACS

for a cardiovascular target

Heart

25000 20000 15000 10000 5000

✱✱

VehicleAZP1R4O1T95A8C42

**significance in Welch test (p 0.005).

TargetProteinlevels Al ( p A h lp aL h I a S L A IS sAig s n ig a n l al)

Source: Pike et al. Drug Discov. Today (2020); Edmondson et al. BioOrg. Med. Chem.

Lett. (2019).

Source: US63/085384 & US63/085376.

Cell therapy approaches focused on regeneration ongoing across all therapy areas

Heart stem cells formed from

embryonic stem cells in six days

Day 0

Day 3

Day 6

HVP1

Antibody purification

HVP cells migrate to injury site after

injection in damaged NHP2 heart

Seeding

Injury site

100 µm

24 hours post injection

Seeding

Injury site

HVP cells - attracted to injury site 48 hours post injection

Increased ejection fraction in

infarcted mice at two months

PlaceboHVP cells

**p < 0.01.

Ejectionfraction%

2. Non-human primate.

1. Human ventricular progenitor cells.

Source: Karl-Ludwig Laugwitz / Kenneth R.Chien.

AI-led small molecule discovery is driving 70% efficacy 50% of small molecule projects are applying AI approaches

In-house

REINVENT platform

Creation, selection and testing of >1060 molecules in silico

Source: Kotsias et al. Nature Machine Intelligence (2020); Blaschke et al. J.Chem.Inf.Model. (2020); Segler et al. ACS Cent Sci (2018); Olivecrona et al. J. Cheminformatics (2017).

In-house AiZynth platform

Chemical reaction prediction to define optimal synthetic route

Predictive science continues to improve our clinical trial performance

Quantitative

modelling

new

old

Sample size per arm in dose range finding study

Quantitative modelling can reduce study size, without impacting probability of success

Probabilitytoselect correctdose(%)

Novel CompEx1

endpoints

SevEx endpoint readout @12months

CompEx endpoint readout @3months

Time in study

Novel endpoints can predict and accelerate efficacy readouts

Participants withoutevents

Continuous

monitoring

Continuously monitored glucose @ week 2

Continuous monitoring can shorten trials and predict earlier success

Clinicalvisitglucose @week7

Advanced

imaging

COPD2 with small airway disease

Advanced imaging can help elucidate potential for disease modification

1. Composite exacerbation.

2. Chronic obstructive pulmonary disease.

Accelerating clinical efficiency through digital innovation

DAPA-MI1 is world's first indication-seeking registry-based randomised controlled outcomes trial

Accelerating and expanding

patient recruitment

Use of registries drives broader patient access, routine clinical follow up and aims to reduce recruitment times by a third

Reducing patient and

Patient app for information

investigator burden

60% reduction in patient burden index compared to DAPA-HF4 by using routinely collected clinical data from the registries

sharing and data collection

Health and trial information, patient reported outcomes and medication use

50% per patient cost reducti

without impacting timelines

AI event

adjudication

Detection and self-report of events

Goal for adjudication in four minutes rather than current four months will accelerate future trial close out

1. Myocardial infarction 2. Cardiovascular.

3. Standard of care 4. Heart failure.

Overall BioPharmaceuticals pipeline

Innovation to fuel sustainable growth

Phase I

Phase II

Phase III

AZD0284 RORg1 psoriasis

anifrolumab

Type I IFN13 receptor LN14

cotadutide GLP-131/glucagon T2D32

MEDI6012 LCAT39 CVAZD7442

LAAB51 combination COVID-19

Fasenra NATRON

IL5R HES59

AZD0449

Inhaled JAK2 inhibitor asthma

anifrolumab

Type I IFN receptor SLE15 SC16

cotadutide GLP-1/glucagon obesity

MEDI6570 LOX-140 CV disease

brazikumab¶

IL23 Crohn's disease

Fasenra OSTRO, ORCHID

IL5R nasal polypsAZD2373 Podocyte health nephropathy

AZD1402# inhaled IL4Ra17 asthma

cotadutide GLP-1/glucagon NASH

MEDI7352 NGF41/TNF42 OA pain

Breztri KALOS LABA52/LAMA53/ICS54 asthma

Fasenra RESOLUTE

IL5R COPDAZD2693

NASH3

AZD4831 MPO18 HFpEF19

cotadutide GLP-1/glucagon DKD33

MEDI7352 NGF/TNF PDN43

Farxiga DAPA-MI

SGLT2 prevention of heart failure and CV death following an MI55

nirsevimab# mAb-YTE60 passive RSV61 immunisationAZD3366 CD39L34 CV5 disease

AZD3427 Relaxin ThP6 CV disease

AZD4041# orexin 1 receptor antagonist opioid use disorder

navafenterol# MABA44 COPD roxadustat# HIF45-PHI46 CIA47 suvratoxumab alpha-Toxin Staphylococcus pneumonia

AZD5718 FLAP20 CKD

Fasenra ARROYO

IL5R34 CSU35

Farxiga DELIVER

SGLT2 HFpEFPT027# ICS/SABA62 asthma

AZD8154 Inhaled PI3Kgd7 asthmaAZD8233

PCSK924 hypercholesterolemiaMEDI3506 IL33 ADtezepelumab#

MEDI0618#

PAR28 antagonist mAb9 OA10

AZD8601# VEGF-A25 cardiovascular

MEDI3506 IL33 COPD

MEDI1341# alpha synuclein Parkinson's disease

AZD9567

SGRM26 CID27

MEDI3506 IL33 asthma

TSLP48 AD tezepelumab# TSLP COPD verinurad URAT149 CKD / HFpEF

Fasenra MESSINA

IL5R EOE58

MEDI1814# amyloid beta Alzheimer's disease

AZD9977+Farxiga MCR28+SGLT229 heart failure

MEDI3506

IL33 COVID-1938

Zibotentan+Farxiga ETA150+SGLT2 CKDMEDI8367 avb811 CKD12

brazikumab IL2330 ulcerative colitisMEDI5884# cholesterol modulation CV

Highlighted in breakout sessions Other pipeline medicines

1. RAR-related orphan receptor gamma 2. Janus kinase inhibitor 3. Non-alcoholic steatohepatitis 4. Ectonucleoside triphosphate diphosphohydrolase-3 5. Cardiovascular 6. Human leukaemia monocytic cell line 7. Phosphoinositide 3-kinases gamma delta 8. Protease activated receptor 2 9. Monoclonal antibody 10. Osteoarthritic pain 11. alpha-v-beta-8 integrin 12. Chronic kidney disease 13. Interferon 14. Lupus nephritis 15. Systemic lupus erythematosus 16. Subcutaneous 17. Interleukin 4 receptor alpha 18. Myeloperoxidase 19. Heart failure with preserved ejection fraction 20. 5-lipoxygenase-activating protein 21. Coronary artery disease 22. Dipeptidyl peptidase 1 23. Chronic obstructive pulmonary disease 24. Proprotein convertase subtilisin kexin 9 25. Vascular endothelial growth factor A 26. Selective glucocorticoid receptor modulator 27. Chronic inflammatory diseases 28. Mineralocorticoid receptor 29. Sodium-glucose co-transporter-2 30. Interleukin 23 31. Glucagon-like peptide 1 32. Type-2 diabetes 33. Diabetic kidney disease 34. Interleukin 5 receptor 35. Chronic spontaneous urticaria 36. Atopic dermatitis 37. Interleukin 33 38. Coronavirus disease 2019 39. Lecithin-cholesterol acyltransferase 40. Lectin-type oxidised low-density lipoprotein receptor 1 41. Nerve growth factor 42. Tumour necrosis factor 43. Painful diabetic neuropathy 44. Muscarinic beta 2-agonist 45. Hypoxia-inducible factor 46. Prolyl hydroxylase inhibitor 47. Chemotherapy induced anaemia 48. Thymic stromal lymphopoietin 49. Urate transporter 1 50. Endothelin receptor A antagonist 1 51. Long-acting antibody 52. Long-acting beta agonist 53. Long-acting muscarinic antagonist 54. Inhaled corticosteroid 55. Myocardial infarction 56. Bullous pemphigoid 57. Eosinophilic granulomatosis with polyangiitis 58. Eosinophilic esophagitis 59. Triple modification, M252Y/S254T/T256E, of the fragment crystallisable region of an IgG antibody which extends its half life - Robbie, G.J., et al. Antimicrob Agents Chemother, 2013. 57(12): p. 6147-53 61. Respiratory syncytial virus 62. Short acting beta agonist 63. Myelodysplastic syndrome # Medicine developed in collaboration ¶ Registrational Phase II/III trial.

Agenda

Q&A

COVID-19 treatment and prevention approaches

Advancing vaccine, antibody, other options

COVID-19 Vaccine

AstraZeneca (C19VAZ)

• UK emergency use authorisation; EU conditional marketing authorisation
• Real world data from UK rollout showing >80% protection against hospitalisation
• US Phase III met the primary endpoint

Granted conditional approval or emergency use in >70 countries

AZD7442 long-acting

antibody (LAAB) combo

• Potential to offer immediate protection
• Late-stage trials in both prophylaxis and treatment
• US Government agreements for potential supply of 700,000 doses in 2021

First data in H1 2021

Other COVID

efforts continue

• Farxiga
DARE-19 Phase III trial
• MEDI3506
ACCORD Phase II trial
• Symbicort
INHASCO Phase IIIa trial
• Pulmicort
TACTIC-COVID Phase IIIa trial STOIC Phase II trial positive

First data in H1 2021

Vaccine development typically takes a decade or longer

C19VAZ: an unprecedented acceleration

Vaccine by 2021

Reduced by 15 years

Vaccine by 2036

Interim analysis

Source: adapted from Plotkin´s Vaccines (7th edition).

COVID-19 Vaccine AstraZeneca

Shown to be safe and effective in clinical trials and real-world data

Protection from hospitalisation and severe disease

First dose protection

Increased efficacy with a longer dosing interval

US Phase III trial primary analysis

100%

efficacy against severe disease, hospitalisation and death

76%

efficacy from day ≥15 after second dose in all adult age groups

85%

efficacy from day 15 after first dose in adults 65 years and over

Real world effectiveness

94%

effective against hospitalisation in enriched elderly population1

80%

effective against hospitalisation in ≥80 years with extensive comorbid disease2

73%

effective from day 35 after first dose in older adults (≥70 years)3

1. Vasileiou E et al. Preprint published online. The Lancet. 2021 2. Bernal JL et al. Preprint published online. The Lancet. 2021 3. Hyams C et al. Preprint published online. The Lancet. 2021.

Clinical priorities

Establishing optimal dosing regimen

Different populations

• Older adults ✓
• Paediatrics - started
• Pregnant women

Heterologous boosting

New variants

AZD7442 long-acting antibody (LAAB) combination

COVID-19 unmet needs persist even during a successful vaccine rollout

AZD7442

• Extended half-life using YTE1
• Intra-muscular administration
• Potent and synergistic combination
• >2% of population immune suppressed2

2021 capacity of 1-2m doses

1. Triple modification, M252Y/S254T/T256E, of the fragment crystallisable region of an

IgG antibody which extends half life - Robbie, G.J., et al. Antimicrob Agents Chemother, 2013. 57(12): p. 6147-53 2. Harpaz, R., et al JAMA. 2016;316(23):2547-2548.

Neutralisation profiles of

therapeutic mAbs3,4

3. Monoclonal antibody 4. Increased Resistance of SARS-CoV-2 Variants B.1.351 and B.1.1.7 to Antibody Neutralization, David D. Ho et al. bioRxiv 2021.01.25.428137.

Phase III trials

• PROVENT and STORMCHASER Phase III trial in pre- and post-exposure prophylaxis; 300mg IM5 dose; potential for 12 months protection
• TACKLE Phase III trial of 600mg IM in outpatient setting and collaborator trials

First data H1 2021

5. Intra-muscular.

Agenda