Meet AZN Management: ASCO 2019

Meet AZN management: ASCO 2019

3 June 2019 Forward-looking statements

In order, among other things, to utilise the 'safe harbour' provisions of the US Private Securities Litigation Reform Act 1995, we are providing 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 we believe our 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 AstraZeneca undertakes no obligation to update these forward-looking statements. We identify 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 our control, include, among other things: the loss or expiration of, or limitations to, patents, marketing exclusivity or trademarks, or the risk of failure to obtain and enforce patent protection; effects of patent litigation in respect of IP rights; the impact of any delays in the manufacturing, distribution and sale of any of our products; the impact of any failure by third parties to supply materials or services; the risk of failure of outsourcing; the risks associated with manufacturing biologics; the risk that R&D will not yield new products that achieve commercial success; the risk of delay to new product launches; the risk that new products do not perform as we expect; the risk that strategic alliances and acquisitions, including licensing and collaborations, will be unsuccessful; the risks from pressures resulting from generic competition; the impact of competition, price controls and price reductions; the risks associated with developing our business in emerging markets; the risk of illegal trade in our products; the difficulties of obtaining and maintaining regulatory approvals for products; the risk that regulatory approval processes for biosimilars could have an adverse effect on future commercial prospects; the risk of failure to successfully implement planned cost reduction measures through productivity initiatives and restructuring programmes; the risk of failure of critical processes affecting business continuity; economic, regulatory and political pressures to limit or reduce the cost of our products; failure to achieve strategic priorities or to meet targets or expectations; the risk of substantial adverse litigation/government investigation claims and insufficient insurance coverage; the risk of substantial product liability claims; the risk of failure to adhere to applicable laws, rules and regulations; the risk of failure to adhere to applicable laws, rules and regulations relating to anti-competitive behaviour; the impact of increasing implementation and enforcement of more stringent anti-bribery and anti-corruption legislation; taxation risks; exchange rate fluctuations; the risk of an adverse impact of a sustained economic downturn; political and socio-economic conditions; the risk of environmental liabilities; the risk of occupational health and safety liabilities; the risk associated with pensions liabilities; the impact of failing to attract and retain key personnel and to successfully engage with our employees; the risk of misuse of social medial platforms and new technology; and the risk of failure of information technology and cybercrime. Nothing in this presentation / webcast should be construed as a profit forecast.

2 Meet AZN management: ASCO 2019 Opening session Agenda

Strategy and business

ASCO 2019 highlights

- Lynparza pancreatic cancer (POLO trial)

- Lynparza 3rd-line ovarian cancer (SOLO3 trial)

- Other highlights

Breakout sessions

4 Cancer is still a growing burden

2018 2030 estimate

18.1 million 26.4 million new patients new patients

9.6 million 17 million deaths deaths

43 million 82 million patients living patients living with cancer with cancer

Source: International Agency for Research on Cancer. 5 Oncology: strategy A leading, diversified oncology business

Lung cancer Multiple cancers Multiple cancers Haematology

trastuzumab deruxtecan

• Stage IV NSCLC1 • Unresectable, • Ovarian, breast • DS4 collaboration • First medicine in T790Mm2 / Stage III NSCLC cancers • Next: HER2+5 haematology EGFRm3 • Next: early / • MRK collaboration breast, gastric • MCL6 launched • Next: adjuvant, advanced stages • Next: pancreatic, cancers; HER2- • CLL7 data started Stage III in several cancers prostate cancers low cancers • Next: combos

‘What’s next’: rich early to mid-stage pipeline, including combinations

1. Non-small cell lung cancer 2. Substitution of threonine (T) with methionine (M) at position 790 of exon 20 mutation 3. Epidermal growth factor receptor mutation 4. Daiichi Sankyo 5. Human epidermal growth factor receptor 2 positive 6. Mantle cell lymphoma 7. Chronic lymphocytic leukaemia. 6 Lung cancer: Tagrisso Realising global opportunity in patients with 1st-line EGFRm disease

Strong performance in all 1st-line opportunity Lifecycle plans include early $m markets: +92% in Q1 2019 is moving global stage and combinations

700 Phase III FLAURA trial almost doubled progression-free survival Phase IIIs in early-stage disease 600 • Adjuvant (ADAURA trial) 500 Tagrisso • Locally-advanced (LAURA trial) 400

300 Phase IIs in post-Tagrisso

200 progression

100 • Savolitinib/MET combination (SAVANNAH trial) 0 Final overall survival data • EGFR, PD-L1, MET, A2aR, CD73, Q1 2016 Q1 2017 Q1 2018 Q1 2019 anticipated in H2 2019 dual EGFR (ORCHARD trial)

US Europe Established rest of world (RoW) Emerging markets Absolute values at actual exchange rates; changes at constant exchange rates (CER) and for Q1 2019, unless otherwise stated. Source: European Society for Medical Oncology meeting 2017. Source: AstraZeneca data on file. 7 Lung cancer: Imfinzi Global adoption underway; lifecycle trials will expand to more patients

Ex-US now 22% of total, Major ongoing Phase III trials $m up from 18% in Q4 2018 with Imfinzi used as backbone

300 AEGEAN ADJUVANT (2020) (2020+)

250 NIAGARA PACIFIC-5 ADRIATIC EMERALD (2020+) (2020+) (2020+) -2 (-)

200 POTOMAC PACIFIC-2 PACIFIC-4 EMERALD- CALLA Stage I-III (2020+) (2020+) (2020+) 1 (2020+) (2020+) 150 Stage IV NILE PEARL CASPIAN (2020+) (2020) (H2 2019) 100 DANUBE POSEIDON NEPTUNE HIMALAYA KESTREL TOPAZ-1 (H2 2019) (H2 2019) (H2 2019) (2020+) (H2 2019) (-) 50 Bladder Lung Liver H&N Cervical Biliary 0 Q4 Q1 Q2 Q3 Q4 Q1 2017 2018 2018 2018 2018 2019 Cancer type

US Europe Established RoW Emerging markets ( ) denote anticipated timeline for data readout. The staging above does not apply to small-cell lung cancer (CASPIAN and ADRIATIC trials) Absolute values at actual exchange rates. Source: AstraZeneca Q1 2019 results announcement. Excludes combination trials where Lynparza is considered the backbone medicine. 8 Lynparza Strong performance; industry-leading development programme

Seven quarters of strong Extensive, strategic development programme underway $m growth: +105% in Q1 2019 Ex-US now 50% of total Novel combinations Earlier lines adjuvant breast of treatment OlympiA Merck combinations 250 1st-line ovarian SOLO-1 Prostate Lung 200 with with 2nd-line abiraterone Imfinzi ovarian Ovarian SOLO-2 150 with cediranib Bladder 3rd-line DDR with 100 ovarian combinations Imfinzi SOLO3 Ovarian with Ovarian Imfinzi 50 with bevacizumab New cancer 0 types Ovarian Breast Pancreas Prostate Study 19 OlympiAD POLO PROfound Q1 2015 Q1 2016 Q1 2017 Q1 2018 Q1 2019

US Europe Established RoW Emerging markets Absolute values at actual exchange rates; changes at CER and for Q1 2019, In collaboration with Merck. unless otherwise stated. Source: AstraZeneca data on file. 9 Trastuzumab deruxtecan and Calquence Important future platforms with significant growth

Trastuzumab deruxtecan: unprecedented efficacy in Haematology taking shape: Calquence heavily-pretreated HER2+ metastatic breast cancer on track to benefit patients globally 59.5% CLL confirmed objective response rate • Study ‘309’ in relapsed/refractory (r/r) patients met primary endpoint; presentation at meeting in June 2019

• Study ‘007’ in front-line patients on track for H2 2019 20.7 months data readout median duration of response1 $m 35 MCL 30 25 Seven • Launched in US 20 median lines of prior treatment 15 and a few global 10 markets 5 0 US regulatory submission in H2 2019 Q4 Q1 Q2 Q3 Q4 Q1 • Sales of $94m 2017 2018 2018 2018 2018 2019 Regulatory decision anticipated in 2020 since launch 1. Not estimable. Source: based on Phase I data, The Lancet Oncology, April 2019. Phase II DESTINY-Breast01 data have not been Absolute values at actual exchange rates. presented yet; trial met primary endpoint in May 2019 and will form the basis for the US regulatory submission. Source: AstraZeneca data on file. 10 Agenda

Strategy and business

ASCO 2019 highlights

- Lynparza pancreatic cancer (POLO trial)

- Lynparza 3rd-line ovarian cancer (SOLO3 trial)

- Other highlights

Breakout sessions

11 ASCO 2019 highlights

Solid AstraZeneca Data highlights from select presence at ASCO 2019 mid-to-late stage trials

• 93 abstracts accepted, including 12 orals and 11 • Lynparza poster discussions Phase III POLO - BRCAm pancreatic cancer Phase III SOLO3 - BRCAm ovarian cancer • Externally-sponsored ~45% of total Phase II TOPARP-B - prostate cancer HRRm1

• Imfinzi 11 Phase III PACIFIC - unresectable, Stage III NSCLC (three-year landmark OS data) 12 • Calquence 11 59 Phase II ACE-CL-208/ACE-CL-003 - CLL

• capivasertib (AKT inhibitor) Phase II FAKTION - ER+2 breast cancer Posters Poster discussions Oral presentations Published only

1. Homologous recombination repair. 2. Eestrogen-receptor positive. Source: AstraZeneca data on file based on submitted and accepted ASCO 2019 Annual Meeting abstracts. Source: ASCO 2019. 12 Agenda

Strategy and business

ASCO 2019 highlights

- Lynparza pancreatic cancer (POLO trial)

- Lynparza 3rd-line ovarian cancer (SOLO3 trial)

- Other highlights

Breakout sessions

13 Lynparza Pancreatic cancer - POLO trial

14 Lynparza Pancreatic cancer - POLO trial

15 Lynparza Pancreatic cancer - POLO trial

16 Lynparza Pancreatic cancer - POLO trial

17 Lynparza Pancreatic cancer - POLO trial

18 Lynparza Pancreatic cancer - POLO trial

19 Simultaneous Lynparza publication in The New England Journal of Pancreatic cancer - POLO trial Medicine

20 Agenda

Strategy and business

ASCO 2019 highlights

- Lynparza pancreatic cancer (POLO trial)

- Lynparza 3rd-line ovarian cancer (SOLO3 trial)

- Other highlights

Breakout sessions

21 Lynparza Ovarian cancer - SOLO3 trial

22 Lynparza Ovarian cancer - SOLO3 trial

23 Lynparza Ovarian cancer - SOLO3 trial

24 Lynparza Ovarian cancer - SOLO3 trial

25 Lynparza Ovarian cancer - SOLO3 trial

26 Lynparza Ovarian cancer - SOLO3 trial

27 Agenda

Strategy and business

ASCO 2019 highlights

- Lynparza pancreatic cancer (POLO trial)

- Lynparza 3rd-line ovarian cancer (SOLO3 trial)

- Other highlights

Breakout sessions

28 Other highlights AstraZeneca continues to redefine cancer treatment

Breaking Treating patients Raising the bar for Advancing treatment earlier in their better outcomes presence in boundaries disease haematology Lynparza Imfinzi Tagrisso Calquence prostate cancer NSCLC NSCLC CLL Phase II TOPARP-B Phase III PACIFIC Phase III FLAURA Phase I/II three-year OS Additional data ACE-CL-003

Lynparza adavosertib Calquence neo-adjuvant ovarian cancer CLL r/r breast cancer Phase II Phase II Phase II GeparOLA ACE-CL-208

capivasertib breast cancer Phase II FAKTION

29 Agenda

Strategy and business

ASCO 2019 highlights

- Lynparza pancreatic cancer (POLO trial)

- Lynparza 3rd-line ovarian cancer (SOLO3 trial)

- Other highlights

Breakout sessions

30 Meet AZN management: ASCO 2019 Breakout 1: sales and marketing Focused Global franchises presence AstraZeneca’s US Japan 81% sales #2 oncology commercial strategy in growth company Oncology: providing the right May May treatment, for the right EU China patient, at the right time, 34% sales #2 oncology Lung cancer growth company3 in the key franchises Lynparza/DDR1 HER22 Haematology

1. DNA damage response. 2. Human epidermal growth factor receptor 2. 32 3. Includes multinational and domestic companies. Sales growth at constant exchange rates and for Q1 2019. Lung cancer: Tagrisso Worldwide 1st-line rollout underway following strong initial launches

Underlying demand Asian patients are especially in focus due continues in the US to higher prevalence of the EGFR mutation

1 • 1st-line EGFRm new- Western Asian patient starts currently at >60% patients patients ~10-15% ~35-40% • Plans underway to EGFRm EGFRm increase EGFRm testing rates • US • Japan • Quarterly total prescriptions >2/3 of sales in 1st line ~2/3 of sales in 1st line volume continues to increase 25,000 • Europe • China 20,000 <1/2 of sales in 1st line NRDL2 in 2nd-line use ensures 15,000 Reimbursement underway; broader access, growth; 1st-line 10,000 ~10 countries so far regulatory decision in mid 2019 5,000

- Anticipated overall survival data readout in H2 2019 Q4 20 15Q1 20 16Q2 20 16Q3 20 16Q4 20 16Q1 20 17Q2 20 17Q3 20 17Q4 20 17Q1 20 18Q2 20 18Q3 20 18Q4 20 18Q1 20 19

1. Epidermal growth factor receptor, mutated. Source: internal specialty pharmacy and specialty distributor data. 2. National Reimbursement Drug List. 33 Lung cancer: Imfinzi US market uptake strong; greater opportunity worldwide

Initiatives to further increase More patient need ex-US; EU reimbursement ongoing benefits to patients in the US

Initiate Extend Treat to only ~1/5 of but ~4/5 of potential early duration progression sales are ex-US patients are ex-US Compared to around half for Lynparza • Emphasise use of Imfinzi immediately following cCRT1 • Japan • Europe, cont. for curative intent 12% of sales UK, Italy and Spain reimbursement underway • Increase HCP2 education for • Europe use of 52 weeks treatment to 8% of sales • China achieve full clinical benefit Reimbursement in France and Regulatory decision in H2 2019 Germany OS3 label anticipated in H2 2019

1. Concurrent chemo-radiation therapy. 2. Healthcare practioner. 3. Overall survival. 34 Lynparza Continuing success in a competitive market

Cementing leadership SOLO-1 data boosting US Lynparza moving fast in ovarian cancer 2nd-line maintenance starts beyond ovarian cancer GY004/GY005 ~80% Combo w/cediranib US market share of PSR1 and PRR2 in ‘all comers’ BRCAm4 breast cancer PAOLA-1 Combo w/bevacizumab 1st-line maintenance PSR ‘all comers’ News flow SOLO-1 • Pancreatic cancer

1st-line maintenance PSR: 1 - Regulatory submission (H2 2019) only PARPi3 with 1st-line data

SOLO-2/Study 19 SOLO approval • Prostate cancer, data readouts PSR maintenance: class leader Phase III PROfound (H2 2019) in 2nd line, with broad label Phase III PROpel (2020+) Jul-18 Apr-18 Oct-18 Jun-18 Jan-19 Feb-18 Mar-18 Feb-19 Mar-19 Nov-18 Dec-18 Aug-18 Sep-18 May-18 SOLO3 • Adjuvant breast cancer First PARPi to show efficacy vs. chemotherapy Data readout (2020+)

1. Platinum sensitive recurrent. 2. Platinum relapsed recurrent. 3. Poly ADP-ribose polymerase inhibitor. Source: Flatiron Health, 3-month rolling data; sample has low numbers. 4. Breast cancer gene, mutated. 35 Trastuzumab deruxtecan in breast cancer and beyond Opportunities across treatment settings in breast cancer

Neo-adjuvant / adjuvant 1st-line metastatic 2nd-line metastatic 3rd-line metastatic

Post neo-adjuvant Replace Replace trastuzumab HER2-positive chemotherapy + Replace Post emtansine breast cancer trastuzumab + pertuzumab trastuzumab emtansine trastuzumab emtansine chemotherapy + trastuzumab + pertuzumab

HR+1: chemotherapy ± endocrine endocrine ± CDK4/6i2 Post CDK4/6i HER2-low therapy breast cancer

TNBC3: chemotherapy Replace 1st-line chemotherapy

Beyond breast Expand into other cancer types: gastric, NSCLC4, CRC5 and others cancer

1.Hormone-receptor positive 2. Cyclin-dependent kinase 4/6 inhibitor 3. Triple-negative breast cancer 4. Non-small cell lung cancer 5. Colorectal cancer. 36 Haematology Calquence Phase III data readout in CLL1 provides momentum

Key data readouts and milestones

Trial/milestone Phase Status

$94m ACE-CL-309 ASCEND in Positive top-line III worldwide Calquence relapsed/refractory CLL results announced sales since launch ACE-CL-007 ELEVATE-TN in Data anticipated III previously-untreated CLL H2 2019

Calquence regulatory Anticipated - 11,000 submissions in CLL H2 2019

patients in relapsed/refractory ACE-CL-006 ELEVATE-RR in Data anticipated CLL, US and EU52 relapsed/refractory high-risk III 2020+ CLL

ACE CL-311 in previously- Data anticipated III 17,000 untreated CLL (w/venetoclax) 2020+ patients in front-line Commercial capabilities established in CLL, US and EU5 MCL3 a solid base for the launch in CLL

1. Chronic lymphocytic leukaemia. 2. EU5 defined as France, Germany, Italy, Spain and UK. Source: company-published sales and epidemiology data. 3. Mantle cell lymphoma. 37 Meet AZN management: ASCO 2019 Breakout 2: late-stage pipeline Lynparza: ovarian cancer Leading development programme across lines of treatment

Study 19: overall survival SOLO-2: progression-free PAOLA-1: 1st-line in ‘all-comer’ 3rd-line+ patients survival in BRACm 2nd line ‘all-comer’ ovarian cancer 1L (complete response; partial response; or non-evidence of disease)

Randomisation (1:2)

Bevacizumab + Bevacizumab + placebo (two years) Lynparza

SOLO3: progression-free survival SOLO-1: progression-free Progression-free survival (PFS1) against CTx1 in BRCAm 3rd line survival in BRCAm 1st line Follow up for second progression (PFS2) or death2

Overall survival1

H2 2019: Phase III data readout 2020: regulatory submission

1. Chemotherapy. Source: Study 19, abstract 5501, ASCO 2016; and Source: SOLO-2, 2 - Late Breaking Abstract, SGO 2017; and 2. Secondary endpoints. SOLO3, abstract 5506, ASCO 2019. SOLO-1, European Society of Clinical Oncology meeting 2018. Source: AstraZeneca data on file. 39 Lynparza: pancreatic and prostate cancers Extending benefit of PARP inhibition1 into new cancer types

POLO: first positive Phase III PROfound: Phase III in mCRPC2 PROpel: Phase III combination trial of a PARPi in gBRCAm HRRm3 (post abiraterone of Lynparza and abiraterone in metastatic pancreatic cancer /enzalutamide) ‘all comer’ 1L mCRPC

Screening Screening

Randomisation Randomisation (1:1)

Active comparator abiraterone + (enzalutamide Lynparza Lynparza or abiraterone) placebo

Treatment until disease progression Treatment until disease progression

Change in radiographic progression-free Locally-determined assessment of rPFS survival (rPFS) during trial period (up to 3 years)

Hazard ratio 0.53 PROfound data anticipated in H2 2019 - PROpel data anticipated in 2020+

2. Metastatic castration-resistant prostate cancer. 1. Poly (ADP-ribose) polymerase inhibitor. 3. Homologous recombination repair mutation. Source: POLO, abstract LBA4, ASCO 2019. Source: AstraZeneca data on file. Source: AstraZeneca data on file. 40 Breast cancer: Lynparza and capivasertib Going into early disease and new mode of action

OlympiAD: first PARP inhibitor OlympiA: gBRCAm Capivasertib (AZD5363): novel, approved in the EU for patients adjuvant breast cancer oral selective AKT inhibitor with gBRCAm HER2-negative Potential in breast, prostate advanced breast cancer Completed definitive local treatment and neoadjuvant or adjuvant chemotherapy

42% Randomisation (1:1) reduction in the risk of disease progression or death vs. standard of care Placebo Lynparza

Treatment for up to a 52% maximum of 12 months objective response rate (ORR) was double that in the chemotherapy arm Invasive disease free survival (IDFS)

OlympiAD approved in EU during H1 2019 - OlympiA Phase III data anticipated in 2020+ Phase III start in Q2 2019

Source OlympiAD, abstract LBA4, ASCO 2017. Source: AstraZeneca data on file. Source: AstraZeneca data on file. 41 Tagrisso: non-small cell lung cancer Focus on early-stage disease and resistance

ADAURA: adjuvant SAVANNAH: EGFRm, MET+ ORCHARD: identifying EGFRm1 NSCLC2 locally-advanced/metastatic resistance / progression factors NSCLC

Stratification: Stage (Ib vs. II vs. IIIa); Patients with NSCLC who pro- Screening EGFRm; and race gressed on 1st-line Tagrisso

Disease progression following treatment Randomisation (1:1) Non-randomised with Tagrisso and MET+ tumour

Placebo Tagrisso Tagrisso + savolitinib Tagrisso + Carboplatin + savolitinib or pemetrexed + Iressa or Imfinzi Treatment for three years from first dose; end of necitumumab treatment assessment 4 weeks after last dose Treatment until disease progression

ORR4 by investigator assessment in accordance Investigator-assessed disease-free survival with RECIST 1.1 ORR

Phase III data anticipated 2020+3 SAVANNAH Phase II data anticipated in 2020+ 1. Epidermal growth factor receptor mutation 2. Non-small cell lung cancer. 3. Based on current expectations and event rates, data from the ADAURA trial can be expected in 2022. 4. Objective response rate. Source: AstraZeneca data on file. Source: AstraZeneca data on file. Source: AstraZeneca data on file. 42 Imfinzi: standard of care in unresectable, Stage III NSCLC Differentially investing to focus on early-stage disease

Unprecedented 11.2 months >50% of patients receiving Early-stage NSCLC trials improvement in median Imfinzi were alive at 36 months progression-free survival

Name Phase Population Data

Neo-adjuvant AEGEAN III (before 2020 surgery) Imfinzi ADJUVANT.31 III Stage Ib-IIIa 2020+ 16.8 months Unresectable, PACIFIC-2 III Stage III 2020+ Placebo NSCLC 5.6 months Unresectable, PACIFIC-4 III Stage III 2020+ NSCLC

Unresectable, Stage III PACIFIC-5 III 2020+ NSCLC (Asia predominant)

Proven progression-free survival Proven overall survival

Source: three-year overall survival update from the PACIFIC trial, abstract Source: Antonia, et al., The New England Journal of Medicine, 2017. 8526, ASCO 2019. Source: AstraZeneca data on file. 43 Late-stage Immuno-Oncology strategy

Major ongoing late-stage Phase III trials Replace Create a new treatment paradigm for patients that replaces CTx Add Generate additional benefits for patients through additive or combination treatment with CTx Early Provide earlier treatment for patients and replace standard of care

Source: AstraZeneca Q1 2019 results announcement. 44 Meet AZN management: ASCO 2019 Breakout 3: early-stage pipeline Rich early to mid-stage pipeline

Tumour drivers and resistance DNA damage response (DDR) Immuno-oncology (IO)

capivasertib (AKT1 inhibitor) adavosertib (WEE15 inhibitor) monalizumab (NKG2A9 mAb10) • breast, prostate cancers, Phase III to start • solid cancers, Phase II • head & neck, colorectal, Phase II ongoing 6 AZD9833 (SERD2, oral) ceralasertib (ATR inhibitor) MEDI5752 (PD-1/CTLA-4 bispecific mAb) • breast cancer, Phase I • solid cancers, Phase II • solid cancers, Phase I AZD5991 (MCL13 inhibitor) AZD2811 (aurora kinase B inhibitor) olecumab (CD7311 mAb) • haematologic cancers, Phase I • solid cancers, Phase II • lung, pancreatic cancers, Phase I/II 7 12 savolitinib (cMET4) AZD1390 (ATM inhibitor) AZD4635 (A2aR inhibitor) • solid cancers, Phase I • NSCLC, Phase II • solid cancers, Phase II AZD7468 (DNA-PK8) AZD9150 (STAT313 inhibitor) • solid cancers • solid cancers, Phase II

1. Protein kinase B 2. Selective oestrogen receptor degrader 3. Induced myeloid leukaemia cell differentiation protein 4. tyrosine-protein kinase Met 5. Tyrosine kinase WEE1 6. Ataxia telangiectasia and rad3-related kinase 7. Ataxia- telangiectasia mutated protein kinases 8. DNA-dependent protein kinase 9. Inhibitory cell surface receptor covalently bound to CD94 10. Monoclonal antibody 11. 5'-nucleotidase 12. Adenosine A2A receptor 13. Signal transducer and activator of transcription 3. 46 Tumour drivers and resistance: early breast Building on an established franchise

Capivasertib (AZD5363): targeting AKT AZD9833 (SERD, oral)

OS in overall population OS in PIK3CA1/AKT/PTEN2 altered

100 100

75 75

50 50

Overall Survival (%) 25 25 Overall Survival (%)

0 0

0 6 12 18 24 30 36 42 0 6 12 18 24 36 Time (months) Time (months) Early evidence of enhanced benefit with capivasertib + paclitaxel in altered metastatic TNBC3

ASCO 2019 data on Tuesday 4 June 2019, abstract #1005:

• OS4 HR5 0.57 in the ITT6 population

Phase I ongoing Phase III to initiate Phase II in planning

1. Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha 2. Phosphatase and tensin homolog. 3. Triple-negative breast cancer 4. Overall survival 5. Hazard ratio 6. Intention to treat. Source: ASCO 2018. 47 Tumour drivers and resistance: cell death Haematologic cancers the next wave of innovation

Targeting distinct nodes of cell death AZD5991 (MCL1 inhibitor)

AZD0466 (Bcl23/xL4i): AZD5991 (MCL1i1): AZD4573 (CDK92i): Single dose of AZD5991 achieves tumour regression in nanomedicine to novel macrocylic distinct mechanism of haematological cancer preclinical models improve therapeutic chemistry targeting MCL1 margin 1 0 0 0 ) 3 m m (

e

m V e h ic le u

l 5 0 0

o 1 0 0 m g /k g V

r o m u T

0 2 8 3 5 4 2 4 9 5 6

AZD5991 in Phase I D a y s P o s t Im p la n ta tio n Single iv dose of AZD5991

1. Inhibitor. 2. Cyclin-dependent kinase 9. 3. B-cell lymphoma 2. Source: Tron AE et al, Nature Communications (9):5341 (2018). 4. B-cell lymphoma-extra large. 48 DNA damage response: Lynparza and beyond Developing chemo-free regimens, extending survival

Launch adavosertib (WEE1) / ceralasertib (ATR) Lynparza combinations

Expand Lynparza beyond BRCA (prostate cancer, Deliver next-generation ovarian cancer) DDR medicines: AZD1390 (ATM inhibitor), AZD2811 (aurora kinase B Establish Lynparza Launch Lynparza inhibitor) leadership as monotherapy combinations (VEGF1, IO) AZD7648 (DNA-PK)

Scientific leadership in DDR

2016 - 2018 2019 - 2021 2022 - 2025

1. Vascular endothelial growth factor. 49 DNA damage response: pipeline The next wave of potential DDR medicines A broad pipeline targeting complementary aspects of DNA damage repair and cell cycle regulation AZD2811: targeting Aurora Kinase B AZD2811 Aurora Bi

adavosertib Death in WEE1i mitosis or subsequent G1 phase Prevent repair M G2 Lynparza PARPi G1 Death in synthesis S (replication) Maximise damage phase Monotherapy activity in SCLC1 model in vivo

AZD0156 AZD7648 ceralasertib AZD0156 ATMi DNA-PKi ATRi ATMi Phase I ongoing adavosertib Lynparza AZD7648 WEE1i PARP1i DNA-PKi Phase II start in planning

1. Poly (ADP-ribose) polymerase. 1. Small cell lung cancer. G1 – growth, S – DNA synthesis, G2 – Growth and preparation for mitosis M – Mitosis. Source: Ashton et al, AACR, 2017. 50 Broad IO pipeline: enhancement of antitumour immunity Fully harnessing immune system to eliminate tumours 1 2 3 No effective Suboptimal or exhausted Antitumour immunity Goal: highly-active antitumour immunity antitumour immunity suppressed by TME1 antitumour immunity

‘Cold’ tumour Example: PD-L1+ tumour Example: CD73+ tumour

Prime Potentiate Reverse tumour Eliminate new response existing response immunosuppression tumour

PD-L1/CD40L2 PD-L1 CD73 IL-123 mRNA4 CTLA-4 A2aR NDV5-GMCSF6 PD-1/CTLA-4 CD39 HPV7 Vaccine NKG2A STAT3

1. Tumour micro environment 2. Cluster of differentiation 40 ligand 3. Interleukin-12 4. Messenger RNA 5. Recombinant Newcastle disease virus 6. granulocyte-macrophage colony-stimulating factor 7. Human papilloma virus. 51 Developing an adenosine franchise Reversing tumour immunosuppression

Targeting adenosine pathway AZD4635: targeting A2aR

IMMUNE RESPONSE

Pro-inflammatory Immunosuppressive

Cancer ↑ MDSC1 ↓ T effectors therapy ↑ Tregs2 ↓ NK3 cells ↑ Dendritic cell ↑ Fibroblast ↑ Tregs 4 ↑ Macrophage ↑ Angiogenesis ↑ Suppressive TAM ↓ Tregs ↑ Angiogenesis Cell death A R P2Y2 A2BR 2A P2X7 CD73

Adenosine CD39 AMP6 ATP5

Phase I ongoing Multiple projects aimed at full suppression Phase II in planning

RCC: renal cell carcinoma. 1. Myeloid-derived suppressor cells 2. Regulatory T cells 3. Natural killer cells 4. Tumour-associated macrophages 5. H&N: head and neck cancer. Adenosine triphosphate 6. Adenosine monophosphate. Source: Merchant et al AACR 2019. 52 Next-generation checkpoints Utilising the innate and adaptive immune system

Monalizumab: targeting NKG2A MEDI5752: PD-1/CTLA-4 bispecific

Tumour: increased efficacy Periphery: increased safety

PD-1 CTLA-4

CTLA-4 CTLA-4 α PD-1 X

α CTLA-4 MEDI5752 α CTLA-4 MEDI5752

Internalisation and degradation of PD-1 Mitigated toxicity due to reduced binding leads to complete and durable blockade to CTLA-4+ peripheral T cells of PD-1 and CTLA-4 in the TME Phase II ongoing Phase I ongoing Phase III in planning Phase II in planning

Source: Cohen et al ESMO 2018. 53 Oncolytic viruses offer multiple mechanisms of action Leveraging internal and external expertise

MEDI5395: NDV-GMCSF Collaboration with Transgene Not a select agent; suitable for world-wide development 1 IFN1γ production, Th21 education

F- Protein Cleavage site modification 2 T cell memory and homeostasis

3 Transgene insertion Incorporation of intergenic stretch Activation of APC s sequence (198nt) 3

MEDI5395 (ICPI <0.2) 4 Immune priming and APC activation

Intracerebral pathogenicity index scale (ICPI): <0.4 is non-pathogenic 5 Increase lysis & Type I IFN response

Phase I in planning Collaboration of five oncolytic viruses

1. Interferon. 2. T helper. Source: Cheng et al, J.Virol 2016 (11). 3. Adenomatosis polyposis coli. 54 Meet AZN management: ASCO 2019 Breakout 4: trastuzumab deruxtecan Trastuzumab deruxtecan A state-of-the-art HER21-targeted, second-generation ADC2

Differentiated ADC

• Higher-intensity chemotherapy (more payload on each antibody)

• Membrane permeability (potential HER2-low applicability) • Selective protease-cleavable linker

• Short half-life of free payload reduces systemic toxicities

Potential best-in-class ADC for Potential first-in-class ADC HER2-positive breast cancer for HER2-low cancers

1. Human epidermal growth factor receptor 2. 2. Antibody drug conjugate. Sources: Daiichi Sankyo R&D event, December 2018, US label for trastuzumab emtansine and Ogitani et al, 2016. 56 Trastuzumab deruxtecan Unprecedented Phase I/II data

Differentiated ADC Phase II primary endpoint met 59.5% confirmed objective response rate 93.7% confirmed disease control rate1

20.7months median duration of response2

Progression-free survival Unprecedented data in advanced Phase II trial met primary in HER2-positive breast cancer HER2-posistive breast cancer endpoint in HER2+ breast cancer

1. Disease control was calculated as the proportion of patients demonstrating complete response, partial response, or stable disease for a minimum of five Source: Phase I, Tamura et al., The Lancet Oncology, 2019. weeks from the first dosing date 2. 95% confidence interval not estimable. 57 Trastuzumab deruxtecan in breast cancer and beyond Opportunities across treatment settings in breast cancer

Neo-adjuvant / adjuvant 1st-line metastatic 2nd-line metastatic 3rd-line metastatic

Post neo-adjuvant Replace Replace trastuzumab HER2-positive chemotherapy + Replace Post emtansine breast cancer trastuzumab + pertuzumab trastuzumab emtansine trastuzumab emtansine chemotherapy + trastuzumab + pertuzumab

HR+1: chemotherapy ± endocrine endocrine ± CDK4/6i2 Post CDK4/6i HER2-low therapy breast cancer

TNBC3: chemotherapy Replace 1st-line chemotherapy

Beyond breast Expand into other cancer types: gastric, NSCLC4, CRC5 and others cancer

1.Hormone-receptor positive 2. Cyclin-dependent kinase 4/6 inhibitor 3. Triple-negative breast cancer 4. Non-small cell lung cancer 5. Colorectal cancer. 58 Trastuzumab deruxtecan Encouraging efficacy in HER2-low breast cancer

HER2-low breast cancer efficacy Percentage change in tumour size from baseline (%) Best percentage change in tumour size from baseline (%)

44.2% objective response rate 9.4 months DoR2, 7.6 months median PFS3

HR: hormone receptor. IHC: immunohistochemistry. 2. Duration of response. Source: poster # p6-17-02, SABCS 2018 (based on 12 October 2018 data cut off). 3. Progression-free survival. 59 Trastuzumab deruxtecan Compelling efficacy in other cancer types

HER2-positive gastric cancer HER2-positive and HER2-mutated NSCLC

N=44 N=11 HER2mut

Three average lines of prior treatment

43% ORR 73% ORR1 5.6 months median PFS 14.1 months median PFS1

Source: abstract #13325, Tsurutani et al, WCLC 2018. Source: Phase I, Shitara et al., The Lancet Oncology. 1. HER2-mutated NSCLC only. 60 Trastuzumab deruxtecan Development plans and news flow

Extensive Phase II/III programme underway News flow

• US FDA BTD2 granted in Aug 2017

2L DESTINY- Breast03 • DESTINY-Breast01 data (2020+) presentation in H2 2019

3L+ DESTINY- • Regulatory decision anticipated in Breast02 (2020+) 2020 • Further Phase III starts anticipated 3L+ To be To be ✓ DESTINY- DESTINY- Phase II To be DESTINY- in 2019-2020 communi- communi- Breast04 Gastric01 Phase II Phase II combo with communi- Breast01 cated cated (2020+) (2020) PD-1 cated (Phase II)

HER2+ HER2+ HER2+ HER2 low HER2+ neoadj adjuvant advanced HER2+ HER2+ bladder Other breast Gastric US regulatory submission breast breast breast CRC NSCLC cancer cancer cancer cancer cancer cancer cancer anticipated in H2 2019

Source: AstraZeneca data on file. 2. Breakthrough Therapy Designation. 61 Investor Relations

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