Meet AZN

management:
Oncology
2021 ASCO Annual Meeting
Dave Fredrickson, Executive Vice
President, Oncology Business Unit

7 June 2021

Interactive event for investors and analysts. This webinar is being recorded.
https://astrazeneca.zoom.us/s/99688625459
 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 intellectual property (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.

2
 AstraZeneca Oncology

We are leading a revolution in oncology to redefine cancer care

Our ambition is to provide cures for cancer in every form.
We are following the science to understand cancer and all its complexities to discover, develop and deliver life-changing treatments and
increase the potential for cure.

Our clinical strategy With our portfolio and

is designed to help pipeline, we strive to
transform survival revolutionalise cancer care

Catalysing changes We are driven by our

in the practice of people, our passion and
medicine to transform our culture of innovation
the patient experience

3
 Oncology: a leading, diversified portfolio1

Lung cancer Multiple cancers Multiple cancers Blood cancers

• Stage IV NSCLC2 • Stage III, unresectable • Ovarian, breast, • Breast cancer (3L9, • Chronic lymphocytic
- EGFRm3 (1L4) NSCLC pancreatic, prostate HER2+10) and gastric leukaemia
- T790M5 (2L6) cancers8 cancer (2L, HER2+)
• Extensive-stage SCLC7 • Mantle cell lymphoma
• Adjuvant EGFRm NSCLC • Merck collaboration • Daiichi Sankyo collab.

Next Next Next Next Next

• Neo-adjuvant and Stage • Early / advanced stages • Adjuvant breast, earlier • Earlier use, HER2 low • Combinations, other
III, unresectable EGFRm of several cancers, use in prostate cancer, and other cancers blood cancers
NSCLC and new combinations combinations (lung, colorectal)
combinations

What’s next:
a rich early to mid-stage pipeline, including combinations and several new Phase III medicines
1. Approved medicines only 2. Non-small cell lung cancer 3. Epidermal growth factor receptor mutation 4. 1st line 5. Substitution of threonine (T) with methionine (M) at position 790 of exon 20 mutation 6. 2nd line 7. Small cell lung cancer 8. Exact patient
population varies by indication 9. 3rd line 10. Human epidermal growth factor receptor 2 positive.
4
 Oncology: strong launch and commercial execution capabilities

Lung cancer Multiple cancers Multiple cancers Blood cancers

$m

1,200 600 600 50 250

1,000 500 500

40 200

800 400 400

30 150

600 300 300

20 100
400 200 200

10 50
200 100 100

0 0 0 0 0
15 16 16 17 17 18 18 19 19 20 20 21 17 18 18 19 20 21 1 5 01 6 01 7 01 8 01 9 02 0 02 1 20 20 20 20 21 17 18 18 18 18 19 19 19 19 20 20 20 20 21
20 20 20 20 20 20 20 20 20 20 20 20 20 20 20 20 20 20 20 2 2 2 2 2 2 20 20 20 20 20 20 20 20 20 20 20 20 20 20 20 20 20 20 20
3 1 3 1 3 1 3 1 3 1 3 1 2 1 4 3 2 1 1 1 1 1 1 1 1 1 2 3 4 1 4 1 2 3 4 1 2 3 4 1 2 3 4 1
Q Q Q Q Q Q Q Q Q Q Q Q Q Q Q Q Q Q Q Q Q Q Q Q Q Q Q Q Q Q Q Q Q Q Q Q Q Q Q Q Q Q Q Q

US Europe Established Rest of World (RoW) Emerging markets

Total revenue at actual exchange rates; product sales only for Lynparza.
5
 90 abstracts with Data
74 presentations highlights
ASCO
2021
• Lynparza
• One plenary session (Lynparza OlympiA Phase III adjuvant breast
Another strong OlympiA Phase III trial) cancer
presence
• 12 oral presentations • Calquence
ELEVATE-TN Phase III 4-year
• 14 poster discussions follow-up
ELEVATE-RR Phase III vs ibrutinib
3rd plenary • 47 posters • Imfinzi
session in a row • 16 abstracts (publication only)
PACIFIC Phase III 5-year overall
survival
• Enhertu, datopotamab
deruxtecan, other potential new
medicines from the pipeline
Source: ASCO 2021 accepted abstracts. 24 additional presentations at ASCO 2021 will feature
AstraZeneca medicines and potential new medicines but were not supported by AstraZeneca.
6
 Agenda Lung cancer

Breast cancer

Haematology

‘What’s next’

Q&A

7
Lung cancer
Mohit Manrao, Global Franchise Head,
Tagrisso and lung cancer
Greg Rossi, Global Franchise Head,
Immuno-Oncology

For additional questions and IR support, please email [email protected].

 Transforming lung cancer by embracing entire patient journey
Translating science to evidence, and evidence to practice
Personalise treatment Diagnose and treat early Improve quality of care

• NSCLC and SCLC • Increase screening and early diagnosis • Integrated remote care
• Tumour drivers and resistance • Digital therapeutics and convenient
• Opportunity for patients to get
mechanisms (TDR) and immuno- treatment in curative setting dosing
oncology (IO) • Healthcare equity and sustainability
• Biomarker-driven treatments across 5-year survival13 % at diagnosis24
EGFR, HER2, exon 141, others
Stage I 68–92% 26%
• Digital pathology and ctDNA2-based Stage II 53–60% 9%
personalised interventions
Stage III 13–36% 25%
(locally advanced)

Now Next Stage IV 0–10% 40%

tremelimumab (metastatic)

savolitinib
ceralasertib
datopotamab deruxtecan Later diagnosis drives
poor outcomes in NSCLC
1. Loss of exon 14 transcription in the mensenchymal-epithelial transition (MET) gene 3. Goldstraw et al., J Thorac Oncol. 2016; 11(1):39–51 4. EpiCast Report: NSCLC
driving tumour growth 2. Circulating tumour DNA. Epidemiology Forecast to 2025, GlobalData, 2016.
9
 Tagrisso: changing treatment expectations in EGFRm NSCLC
Continuing to push the boundaries of science and patient care
Reshaping the treatment paradigm Enabling maximal patient benefit globally
by moving into earlier lines of NSCLC Globally Embedded Access
Globally-embedded access
1
• First EGFR TKI to overcome T790M resistance
2L 2L 67 91
2015 • Best-in-class blood-brain barrier penetration
• Excellent tolerability profile, convenient oral dosing Including
China NRDL
• 1L EGFR standard of care
1L 44 90
2017 1L • Only EGFR TKI with OS2 > 3 years and unsurpassed PFS3
Reimbursed/Early Access
• Best-in-class CNS4 risk reduction 8 55
Adjuvant 22 App roved

2020 Adjuvant
Strong momentum in patient reach > 250,000
Unparalleled Stage IB-IIIA efficacy (80% relative risk) 210,274

§ Protection against
distant recurrences, 96,770
including in the CNS
§ Strongest-rated 29,466
3,812 10,365
curative-intent therapy
in NSCLC (ESMO-MCBS)
2016 2017 2018 2019 2020 2021 YTD

Established clinical leadership Bench to bedside excellence

1. Tyrosine kinase inhibitor 2. Overall survival 3. Progression-free survival 4. Central nervous system.
Source: abstract LBA5, ASCO 2020. Source: AstraZeneca.
10
 Tagrisso: building new EGFRm standard of care in NSCLC
Clinical trials across the NSCLC continuum
Early stage Late stage
Resectable Unresectable 1st line 2nd line+

Stage I-II AURA3

FLAURA Post-Tagrisso combinations

Neo-
Stage IA ADAURA ORCHARD | SAVANNAH
ADAURA Other combinations
LAURA

FLAURA2 Non-T790 1/2G resistance

1 2
Further embed leadership position within earlier-stage Define and deliver innovative combinations with Tagrisso as
curative-intent setting with the strongest potential for a backbone in 1st line and beyond 1st-line Tagrisso
clinical and economic value creation monotherapy

Approved indications Ongoing trials Approved indications Ongoing trials

11
 Enhertu, datopotamab deruxtecan: ADC1 portfolio
Significant activity across NSCLC
Enhertu - HER2 ADC (DESTINY-Lung01 trial) Datopotamab deruxtecan - TROP26 ADC
(TROPION-PanTumor01 trial)
ORR2 62%, mPFS 14m Best Overall Response (BICR)
(n=39, 6.4mg/kg, 2L median prior Tx, 76% post-PDx3)
HER2m4 NSCLC 2L+ NSCLC
~2% prevalence
NCCN5 listing March 2021

ORR 25%, mPFS 5.4m

(n=44, 6.4mg/kg, 3L median prior Tx, 74% post-PDx)
HER2+ NSCLC
~15% prevalence

Planned trials: TROPION-Lung01: EGFR / ALK WT7 2-3L, Phase III

Planned trial: DESTINY-Lung02: 2L+, Phase II in HER2m NSCLC, further evaluation of TROPION-Lung02: 1L, Phase I pembrolizumab combo ± platinum chemo
dose 5.4 mg/kg TROPION-Lung04: 1L, Phase I Imfinzi combo ± platinum chemo
DESTINY-Lung 03: 1L Enhertu + durvalumab + chemo Phase I TROPION-Lung05: Driver positive after TKI and platinum chemo 3L, Phase II
1. Antibody drug conjugate 2. Objective response rate 3. Post PD-1 or PD-L1 checkpoint inhibitor 4. HER2 mutated 5. National 6. Trophoblast cell-surface antigen 2, a transmembrane glycoprotein that is overexpressed in many cancers 7. Anaplastic
Comprehensive Cancer Network. Source: abstract OA04.05, World Conference on Lung Cancer (WCLC) 2020; HER2m and HER2+ lymphoma kinase wild type.
(IHC2+/3+) prevalence, AstraZeneca data and Miller et al., Syst 2015, Oh and Bang et al., Nature Oncology Reviews, 2017. Source: abstract 9085, ASCO 2021.
12
Imfinzi: immuno-oncology
Unique position in lung cancer
Comprehensive programme in Strong launch Novel
early lung builds on PACIFIC in ES-SCLC2 combinations
PACIFIC updated OS (ITT1) CASPIAN HUDSON Phase II
+ ceralasertib
A SCO 2 0 2 A SCO 2 0 2 W C LC 2 0 2
1 0 0

• 43% of patients alive at five years • Only IO medicine with two-year OS published data • Post-checkpoint inhibitor use - overcome immune
• 33% progression free at five years • 3-year exploratory data anticipated in H2 2021 checkpoint resistance through ceralersertib + Imfinzi
combination

Ongoing Phase III trials: Ongoing Phase II trials:

Unresectable: PACIFIC-2, PACIFIC-4, PACIFIC-5, Ongoing Phase III trials: HUDSON (advanced NSCLC post CPI3), MAGELLAN (1L
PACIFIC-8 Limited stage: ADRIATIC NSCLC), NeoCOAST (resectable NSCLC, neoadjuvant),
Resectable: AEGEAN, BR.31, MeRmaiD 1/2 COAST (Imfinzi + novel MoAs4)

1.Intention to treat. 2. Extensive-stage small cell lung cancer. 3. Checkpoint inhibitors 4. Mode of action.
Source: abstract 8511, ASCO 2021. Source: Journal of Clinical Oncology 38, no. 15_suppl (20 May 2020) 9002-9002. Source: abstract OA07.08, WCLC 2020.
 NSCLC: leadership across the spectrum
Potential to cover most patients across settings and lines of treatment
Stage I-IIIB
neo-adjuvant Stage I-IIIB
resectable/ early/adjuvant Stage I-IIIB Metastatic Metastatic
unresectable resectable unresectable 1st line 2nd line+

EGFR Tagrisso monotherapy and

Tagrisso
combinations
Enhertu mono
HER2
and combo
Other tumour savolitinib
drivers and
resistance “What’s next”

Imfinzi monotherapy and combinations

Immuno-
oncology and
non-TDR datopotamab
deruxtecan
mono and combo

Illustrative; not to scale.

14
Breast cancer
Cristian Massacesi, Senior Vice President,
Oncology R&D, late-stage development
Sunil Verma, Vice President, Oncology R&D,
late-stage development breast cancer

For additional questions and IR support, please email [email protected].

 Breast cancer: AstraZeneca’s pioneering medicines have helped
patients for more than four decades

1970’s 1980’s 1990’s

On the World Health Organization’s list of Lutenising hormone-releasing agonist of choice for One of the gold-standard medicines for
essential drugs for the treatment of breast cancer ovarian suppression in premenopausal women with postmenopausal HR+ breast cancer for years
breast cancer

2000’s 2010’s 2020’s

The current endocrine therapy of First targeted treatment option for patients with BRCA- Transformative HER2-directed medicine that has
choice in metastatic breast cancer mutated breast cancer both in the metastatic and early started to redefine the way physicians classify and
breast cancer setting treat HER2-expressing breast cancer

16
 Breast cancer: AstraZeneca has a bold 10-year ambition to
transform survival

Smarter Earlier Harder

Redefine the treatment paradigm and Bring impactful medicines where Establish foundational medicines that
enable a more personalised approach there is an opportunity for cure set new benchmarks in outcomes

Utilise Innovative
Biomarkers Improve
technology medicines
outcomes

ctDNA Overcome Displace/ Novel

Subtypes applications resistance replace combinations
Identify SoC1

1. Standard of care.
17
 Lynparza: potential new standard of care
Now BRCAm adjuvant breast cancer
Lynparza demonstrated a sustainable and clinically
relevant treatment effect versus placebo for patients1
2.3 million
women diagnosed with
breast cancer in 2020

5%
breast cancer patients with
BRCA mutation

50%
of women diagnosed with BRCAm breast
cancer are younger than 55 years of age

1. With germline BRCA-mutated (gBRCAm) high-risk human epidermal growth factor receptor 2 (HER2)-negative early breast cancer.
Source: abstract LBA01, plenary session, ASCO 2021. Source: AstraZeneca.
18
 Enhertu: transforming HER2+ and redefining HER2-low BC
Clinical development programme across multiple lines and subtypes
Launched in 3L, HER2+ mBC1 BEGONIA: Imfinzi + Enhertu, Upcoming Enhertu breast
HER2-low 1L mTNBC2 cancer data readouts
• Total revenue $40m; US $35m in Q1 2021
$73m US in-market sales by Daiichi Sankyo
H2 2021
• Strong patient share • DESTINY-Breast03 (2L, HER2+)
Most prescribed medicine in HER2+ mBC;
c.5,000 patients treated 2022
• EU regulatory approval • DESTINY-Breast02 (3L, HER2+)
January 2021 • DESTINY-Breast04 (HER2 low)

2022+
• Multiple trials across HER2+,
HER2 low and earlier disease

ASCO 2021: data demonstrates Benefit observed in HER2 1+ Multiple Phase III
Enhertu’s strong CNS activity and HER2 2+/ISH3-ve by local test trials underway
2. Metastatic triple-negative breast cancer.
1. Metastatic breast cancer. 3. In situ hybridisation.
Collaboration revenue at actual exchange rates. Source: poster 1023, ASCO 2021.
19
 Enhertu: clinical development programme
Opportunities across breast cancer, HER2-low and other tumours
Neo-adjuvant / adjuvant 1L metastatic 2L metastatic 3L metastatic

2x Phase III

HR+1: chemotherapy ± endocrine Post

HER2-low therapy
endocrine ± CDK4/6i2
CDK4/6i
breast cancer

HR-3: chemotherapy Replace/displace chemotherapy

Post neo-adjuvant
replace trastuzumab
emtansine
Phase III Phase III Phase III ✓
US, EU & JP
Replace
HER2-positive chemotherapy +
Replace Post approval

breast cancer trastuzumab + pertuzumab

trastuzumab emtansine trastuzumab emtansine
chemotherapy + trastuzumab + pertuzumab

Beyond
Expand into other cancer types: gastric, NSCLC, CRC4 and others
breast cancer

1. Hormone-receptor positive 2. Cyclin-dependent kinase 4/6 inhibitor 3. Hormone-receptor negative 4. Colorectal cancer.
20
 Breast cancer: competitive late-stage breast cancer pipeline
Phase III trials underway and planned
Capivasertib (AZD5363): Camizestrant (AZD9833): Datopotamab deruxtecan
oral AKT inhibitor next-generation oral SERD (DS-1062): TROP2 ADC

Breast Phase III trials underway Encouraging monotherapy efficacy

• CAPItello-291, 2L breast cancer: and dose-dependent safety profile
capivasertib + Faslodex

• CAPItello-292, 1L advanced:
16.3%
overall response rate
capivasertib + Faslodex + CDK4/6i

TNBC Phase III trial underway

• CAPItello-290, metastatic TNBC:
42.3%
clinical benefit rate
capivasertib + chemo

Promising preliminary activity in heavily

Address endocrine resistance; evaluate Phase III trials underway and planned
pre-treated TNBC population;
different endocrine combinations SERENA-4 data anticipated 2022+
favourable profile vs. SoC
N.B. Faslodex provided ~5-10% ORR in similar setting.
Source: abstract 1005, ASCO 2019; abstract 1007, ASCO 2018. Source: abstract 1024, ASCO 2020.
21
 Breast cancer: well-positioned with at least six medicines
Potential to cover most patients across settings and lines of treatment
Early/curative setting Metastatic setting
Neo-adjuvant Adjuvant 1st line 2nd line 3rd line 3rd line+
HER2+ Enhertu monotherapy Enhertu monotherapy
c.20% of patients and potential combos and potential combos

datopotamab
camizestrant camizestrant deruxtecan
camizestrant
Hormone-
receptor HER2 low
positive (HR+) c.55%1 of patients
capivasertib
c.65% of patients that are not HER2+ capivasertib combinations Enhertu
datopotamab
capivasertib deruxtecan
combinations

Enhertu

Lynparza (BRCAm) Lynparza (BRCAm)

Triple-negative
ADC after ADC +/- IO Enhertu
(TNBC)
c.15% of patients ADC2 +/- IO3 neo-adjuvant capivasertib + CTx4
1. HER2-low prevalence is anticipated to be c.35-40% in
TNBC 2. Antibody drug conjugates (Enhertu and datopo-
Illustrative; includes trials planned. tamab deruxtecan) 3. Immunotherapy 4. Chemotherapy.
22
Haematology
Niko André, Global Franchise Head,
Haematology and Calquence
Anas Younes, Senior Vice President,
Oncology R&D, haematology

For additional questions and IR support, please email [email protected].

 Calquence: a standard of care in chronic lymphocytic leukaemia

Relapsed/refractory (R/R) Front line (FL)

ASCEND Phase III trial ELEVATE-TN Phase III trial
IRC-Assessed Progression-Free Survival
• Font: Calibri 18pt. Median follow-up 28.3 months
100
93%

• Box, bullets to match header colour

Progression-free survival (%)

80 87%

• Text or graphics
Hazard ratio
Acala-G
60 vs G-Clb
47% Acalabrutinib
vs G-Clb
40
Acala-G vs
acalabrutiniba

20
Acala-G
Acala
G-Clb (Median PFS 22.6 months [95% CI 20.2, 27.6])
0
0 6 12 18 24 30 36 42
Number at risk Months
179 176 170 168 163 160 159 155 109 104 46 41 4 2
179 166 161 157 153 150 148 147 103 94 43 40 4 3
177 162 157 151 136 113 102 86 46 41 13 13 3 2

Kaplan-Meier estimates performed by IRC and all analyses for the intention-to-treat population. No. of events: Acala-G, 14 (7.8%); Acala, 26 (14.5%); G-Clb, 93 (52.5%)
a Post hoc analysis.

Richter’s transformation occurred in: Acala-G n=1, Acala n=5, G-Clb n=1 HR (95% CI)
Calquence + obinutuzumab vs 0.10
HR1 (95% CI) chlorambucil + obinutuzumab (0.06-0.17), p<0.0001

Calquence vs 0.31 Calquence vs 0.20

IdR/BR (0.20-0.49), p<0.0001 chlorambucil + obinutuzumab (0.13-0.30), p<0.0001

From a PFS HR of 0.31 …to a HR of 0.20 for mono and 0.1

in the R/R setting… for combinations in the FL setting
1. Hazard ratio.
Other notes: IdR = idelalisib BR = bendamustine and rituximab.
Source: abstract LB2606, The European Hematology Association 2019. Source: abstract 31, The American Society of Hematology, 2019.
24
 Calquence: launch trajectory confirms clinical value
Inflection point from chronic lymphocytic leukaemia uptake
Solid launch US: high up- Ex-US: Europe launch and
$m trajectory take in CLL2 reimbursement underway
250
• CLL c.3/4 of all Calquence use • Approval
60 countries (CLL) and 27 (MCL3)
200
• >10% growth in CLL patient starts
on BTKi1 despite COVID-19 impact • Reimbursement
150 10 countries (CLL) and 9 (MCL)
• 1st line: >40% new-patient share
100 with BTKi use c.40% of all patients • Sales in >25 countries
Largest contribution from DE, UK,
50
• Large opportunity in reducing FR
chemotherapy use in front line
0
17 018 018 018 018 019 019 019 019 020 020 020 020 021 New-patient share in BTK Accelerating uptake
20 2 2 2 2 2 2 2 2 2 2 2 2 2
Q
4
Q
1
Q
2
Q
3
Q
4
Q
1
Q
2
Q
3
Q
4
Q
1
Q
2
Q
3
Q
4
Q
1
class now more than 40% after reimbursement
US Europe Established RoW Emerging markets 1. Bruton’s tyrosine kinase inhibitor.
2. Chronic lymphocytic leukaemia.
Product sales at actual exchange rates. Source: IQVIA market research. 3. Mantle cell lymphoma.
25
 Calquence: CLL launches
Global rollout in three waves

1st wave 3rd wave

Approval
Regulatory
US Q4 2019
submission
CN 2022
93% of sales
in Q1 2021 2nd wave
Approvals
EU Q4 2020
JP Q1 2021

Launch in DE, FR, UK

with IT, ES in H2 2021

26 Sales in >25 countries

 Calquence at ASCO: ELEVATE-TN Phase III trial
Sustained patient benefit at four years in a front-line setting

Overall population

Patients with del(17p)

and/or mutated TP53

Hazard ratio was based on unstratified Cox-Proportional-Hazards model; P-value was based on unstratified log-rank test.
Notes: A = Calquence (acalabrutinib) O = obinutuzumab, a 2nd-generation CD20 monoclonal antibody Cb = chlorambucil, a standard-of-care chemotherapy.
Source: abstract 7509, ASCO 2021.
27
 Calquence at ASCO: ELEVATE-RR Phase III trial vs. ibrutinib
Lower incidences of any-grade atrial fibrillation/flutter; solid safety overall

Afib/Flutter
Calquence (acalabrutinib)
Calquence (acalabrutinib)
Any grade Grade ≥3
Acalabrutinib Ibrutinib Acalabrutinib Ibrutinib
Events, n (%) (n=266) (n=263) (n=266) (n=263)
Cardiac events 64 (24.1) 79 (30.0) 23 (8.6) 25 (9.5)
Atrial fibrillationa* 25 (9.4) 42 (16.0) 13 (4.9) 10 (3.8)
Ventricular arrhythmiasb 0 3 (1.1) 0 1 (0.4)
Bleeding events* 101 (38.0) 135 (51.3) 10 (3.8) 12 (4.6)
Major bleeding eventsc 12 (4.5) 14 (5.3) 10 (3.8) 12 (4.6)
Hypertensiond* 25 (9.4) 61 (23.2) 11 (4.1) 24 (9.1)
Infectionse 208 (78.2) 214 (81.4) 82 (30.8) 79 (30.0)
ILD/pneumonitis* 7 (2.6) 17 (6.5) 1 (0.4) 2 (0.8)
SPMs excluding NMSC 24 (9.0) 20 (7.6) 16 (6.0) 14 (5.3)

Higher incidence indicated in bold yellow for terms with statistical differences.
*Two-sided P-value for event comparisons <0.05 without multiplicity adjustment.
aIncludes events with preferred terms atrial fibrillation and atrial flutter.
bIncludes events with preferred terms torsade de pointes, ventricular arrhythmia, ventricular extrasystoles, ventricular fibrillation, ventricular flutter, ventricular tachyarrhythmia, and ventricular tachycardia.
cDefined as any hemorrhagic event that was serious, grade ≥3 in severity, or a central nervous system hemorrhage (any severity grade).
dIncluded events with the preferred terms of hypertension, blood pressure increased, and blood pressure systolic increased.
eMost common grade ≥3 infections were pneumonia (acalabrutinib, 10.5%; ibrutinib, 8.7%), sepsis (1.5% vs 2.7%, respectively), and UTI (1.1% vs 2.3%).

ILD, interstitial lung disease; NMSC, nonmelanoma skin cancer; SPMs, second primary malignancies; UTI, urinary tract infection.

Notes: Afib = atrial fibrillation; irregular heartbeat (arrhythmia) CI = confidence interval.

Source: abstract 7500, ASCO 2021.
28
 Haematology: projects in early development
Emerging pipeline in main haematology indications
Broad portfolio First immunotherapy Tumour drivers
in cell death bispecific antibody of resistance

Target/
medicine Bcl-21 Bcl-xL BFL1 MCL12
idelalisib
venetoclax duvelisib
PD-19 TIM3 copanlisib
AZD0466
(Bcl-2/xL) ✓ ✓
capivasertib
AZD5991
(MCL1) ✓ Cκ Cλ
everolimus
AZD4573
(CDK93) ✓ ✓ temsirolimus

Potential in: Potential in: Potential in:

AML4, MDS5, NHL6, HL7, PTCL8 Hodgkin lymphoma follicular lymphoma, MCL
1. B-cell lymphoma 2 2. Induced myeloid leukaemia cell differentiation protein 3. Cyclin-
dependent kinase 9 4. Acute myelogenous leukaemia 5. Myelodysplastic syndromes 6. Non- 9. Programmed cell death protein 1. Source: modified from Nature
Hodgkin lymphoma 7. Hodgkin lymphoma 8. Peripheral T-cell lymphoma. Source: AstraZeneca. (https://www.nature.com/articles/nrclinonc.2016.205).
29
 Haematology: ‘What’s next’
Growing pipeline across medicines and indications
AML/
CLL/SLL1 MCL DLBCL2 FL/MZL3 MM4 Other
MDS
Tumour drivers of resistance Calquence (BTK)
capivasertib (AKT)
New targets
Cell death AZD4573 (CDK9)
AZD5991 (MCL1)
AZD0466 (Bcl-2/xL)
New targets
IO / bispecifics / cell therapy New targets
Epigenetics AZD5153
New targets
ADCs New targets

Current Emerging
Launched
portfolio portfolio

1. Small lymphocytic lymphoma 2. Diffuse large B-cell lymphoma 3. Marginal zone lymphoma 4. Multiple myeloma.
30
‘What’s next’
Susan Galbraith, Senior Vice President,
Oncology R&D, early stage
Andrew Mortlock, Vice President,
Oncology R&D, haematology projects

For additional questions and IR support, please email [email protected].

 Comprehensive portfolio to combat cancer

Oncology ambition Attained through diversity in portfolio

Tumour drivers Oncogenic truncal drivers and

Redirect local immunity Immune and resistance mechanisms of resistance
Awaken dormant immune cells engagers
Tumor burden

DNA damage Synthetic lethality exploiting

” response impaired DNA damage response
Build synthetic immunity
axis
Infuse with engineered T cells Cell therapy re
no
“Ig Antibody drug
conjugates
Replacing standard
Activate
Targeted delivery of Oncolytic Direct of care (i.e. chemo)
1 medicines that recruit virus immune Radioimmuno- with targeted
immunity system killing conjugates delivery of toxic
3 Microenvironment Tumour molecules
Diagnosis “D Nanomedicines
Long-term ef
by ctDNA survival and en
d
cure ax
2 4 is”
Build on PDx
Overcome immune Immuno-oncology
suppression
Time
Epigenetics Reprogramming tumour cells

Source: AstraZeneca.
32
 What’s next?
Selectively expanding technologies and platforms
DDR Next-wave IO Next-wave modalities

AZD2811
(Aurora B kinase)
ATTACK

Adavosertib
(WEE11 )
ADCs & RIC4s
Death in mitosis

Prevent repair
M Eliminate
G2 tumor

G1
Acquired resistance

PROTAC5s
Lynparza
(PARPi)
S

Maximise damage

AZD6738 Tumor escape

(ATR2 )
AZD0156
(ATM)

IGNORE DEFEND
Functional genomic
capabilities

1. Tyrosine kinase WEE1 2. Ataxia telangiectasia and rad3-related kinase. Source: AstraZeneca. 4. Radioimmunoconjugate 5. Proteolysis targeting chimeras.
33
 Advancing the DDR portfolio
Key data at ASCO and AACR
AZD5305 EFFORT HUDSON
PARP-1 selective inhibitor Adavosertib Phase II trial Umbrella NSCLC platform post-IO
Adavosertib monotherapy
• Five abstracts at AACR1
• Selective PARP1-DNA trapper
20% increase

• More potent and efficacious than first-

generation PARP inhibitors 30% reduction ORR2: 23%
DOR3 5.5 months
PFS 5.5 months

Strong
combination Adavosertib and Lynparza
activity with
20% increase
carboplatin
(non-BRCA
setting)
30% reduction ORR: 29%
DOR 5.5 months
PFS 6.4 months

AZD5305 now WEE1 activity in ATR activity in combination with

in Phase I trials PARP-resistant patients Imfinzi in IO-pretreated patients
2. Overall response rate 3. Duration of response.
1. American Association for Cancer Research. Source: abstract 5505, ASCO 2021. Source: abstract OA07.08, WCLC 2020.
34
 Next-wave IO
Clinical-stage progress
Key Phase II Imfinzi AZD7789 AZD8853
combination trial readouts PD1/TIM3 bispecific Anti-GDF15
OE21
OE21 Humanised
10xGS
10xGS -v3 mouse model
-v3 OE21 10xGS- V3
Imfinzi + oleclumab (CD731) or 1500
1500
R347
R347 Isotype
Isotype
Survival
Ctl Ctl

Percent Survival
aPD1 LO115

Tumor Volume (mm3)

100 aPD1 LO115

monalizumab (NKG2A2)

Tumor Volume (mm3)

MEDI7789
MEDI7789 - PD1/TIM3
- PD1/TIM3 Duet
Duet MabMab

Percent survival
1000 80
1000

*** 60

• COAST (Stage III unresectable NSCLC) 500500 * 40 Iso Ctl

* 20
Iso Ctl- R347
Anti-PD1
aPD1 LO115
MEDI7789

• NeoCOAST (early-stage NSCLC)

AZD7789
0 0 0
0 20 40 60 80 100
0 0 20 20 40 40 60 60 80 80
Study
Study Days
Days Study Days

Imfinzi + ceralasertib (ATR)

• Potential to address patients who either don’t
benefit from IO or benefit but still eventually Lewis lung (LL/2) syngeneic model (insensitive to
• HUDSON (NSCLC) progress PD1/L1) treated with anti-GDF15 Ab -5/12 mice had
• MONETTE (melanoma) • May help to reverse resistance complete responses

GDF15 regulates DC activation, T cell

COAST/NeoCOAST data Targeting PD-1/TIM-3 increases survival recruitment and monocyte/macrophage
presentation H2 2021 in IO-naïve & PD-1 resistant models immunosuppression

1. 5'-nucleotidase 2. NKG2-Atype II integral membrane protein. Source: AstraZeneca. Source: AstraZeneca.

35
 Next-wave modalities
Innovative use of new modalities to deliver transformational change
ADCs & RICs PROTACS Genomics capabilities
Pharmacology, CRISPR screens and DepMap-
6 stability
enhancing target identification
PK/PD, Kd, Tox, TI

1 Target
density

5 Warhead
MOA

Internalisation
2 kinetics

4 Bystander
kill activity

3 Lysosomal
trafficking vs.
recycling

Targeted killing by targeting proteins Harnessing the cell’s natural Selective targeting of the key
immune to conventional approaches waste disposal system resistance and survival pathways

Source: AstraZeneca. Source: AstraZeneca. Source: AstraZeneca.

36
 Early-stage oncology pipeline

Phase I Phase II
MEDI1191 AZD0466 oleclumab
modIL-12 BcI2-xL CD73

IPH5201 AZD5991 imaradenant

CD39 MCL1 A2AR1

AZD5069 AZD1390 MEDI5752

CXCR2-ESR ATM PD-1/CTLA42

AZD0171 AZD7648 MEDI0457

LIF1 DNAPK HPV Vax

AZD8701 AZD5305 camizestrant

FOXP3 ASO PARP1Sel SERD

MEDI5395 AZD4573
rNDV GMCSF CDK9

MEDI9253 ceralasertib
rNDV IL-12 ATR

AZD5153 AZD2811
BRD4-ESR AURN

Immuno-oncology Haematology

Oncolytic virus Tumour drivers and resistance

Epigenetics DNA damage response

1. Adenosine A2A receptor 2. Cytotoxic T-lymphocyte-associated protein 4.

37
 ‘What’s next’
Phase I/II new medicines, selected

What’s now Phase III new medicines

datopotamab deruxtecan camizestrant

lung cancer breast cancer

monalizumab capivasertib
head & neck cancer breast, prostate cancer

adavosertib ceralasertib
savolitinib tremelimumab
(WEE1 inhibitor) (ATR inhibitor)
NSCLC1 multiple cancers
uterine, ovarian cancer solid tumours, blood cancers

oleclumab imaradenant
(CD73 mAb) (A2AR inhibitor) Phase III lifecycle management, major
solid tumours solid tumours

AZD5305 MEDI5752
Lynparza
(PARP1 inhibitor) (PD-1/CTLA4 mAb)
multiple cancers
solid tumours solid tumours

AZD4573 AZD2811
Tagrisso Enhertu
(CDK9 inhibitor) (Aurora B inhibitor)
NSCLC multiple cancers
blood cancers solid tumours, blood cancers

AZD5991 AZD0466
Imfinzi Calquence
(MCL1 inhibitor) (Bcl-2/xL)
multiple cancers multiple cancers
blood cancers solid tumours, blood cancers

1. Potentially pivotal Phase II.

38
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