Investor Relations General Presentation

Investor RelationsGeneral PresentationGeneral Presentation

March 2015

Cautionary statement regarding 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 presentation contains certain forward-looking statements with respect to the operations, performance and financial condition of the G Alth h b li t ti b d bl ti f d l ki t t t b th iGroup. 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 presentation 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 patents, marketing exclusivity or trade marks, or the risk of failure to obtain patent protection; the risk of substantial adverse litigation/government investigation claims and insufficient insurance coverage; exchange rate fluctuations; the risk that R&D will not yield new products that achieve commercial success; the risk that strategic alliances and acquisitions will be unsuccessful; the impact of competition, price controls and price reductions; taxation risks; the risk of substantial product liability claims; the impact of any failure by third parties to supply materials or services; the risk of failure to manage a crisis;product liability claims; the impact of any failure by third parties to supply materials or services; the risk of failure to manage a crisis;the risk of delay to new product launches; the difficulties of obtaining and maintaining regulatory approvals for products; the risk of failure to observe ongoing regulatory oversight; the risk that new products do not perform as we expect; the risk of environmental liabilities;the risks associated with conducting business in emerging markets; the risk of reputational damage; the risk of product counterfeiting;the risk of failure to successfully implement planned cost reduction measures through productivity initiatives and restructuringprogrammes; the risk that regulatory approval processes for biosimilars could have an adverse effect on future commercial prospects; and the impact of increasing implementation and enforcement of more stringent anti-bribery and anti-corruption legislation.Nothing in this presentation should be construed as a profit forecast.

2

Page

ContentsPage

1. Strategy 42. Business Overview 14 3. Respiratory, Inflammation & Autoimmunity (RIA) 184. Cardiovascular & Metabolic Disease (CVMD) 375. Oncology 536. Infection, Neuroscience & Gastrointestinal (ING) 867. Emerging Markets / Japan 908. Finance 1029 A di 1129. Appendix 112

3

Strategy

Strategic priorities

1 2 3Achieve scientific

Be a great place to work

Return to growth

1 2 3leadership

pg

FOCUS on distinctive science in FOCUS on key growth platforms FOCUS on simplification of3 main therapy areas

PRIORITISE & ACCELERATEour pipeline

FOCUS on key growth platforms

ACCELERATE through business development

DRIVE continued productivity improvements

our business

TRANSFORM our innovation culture & model

TRANSFORM through specialty care / biologics EVOLVE our culture

5

Completing the first phase of the journey

>$45bn in 2023

2012-2014Building strong

foundations

2018+Sustainable delivery

and growth

2015-2017Delivering on return

to growthfoundations and growthto growth

6

Focus:R&D in 3 main therapy areas & across key platforms

Cardio-Metabolism

Respiratory/ inflammation Oncology

NeuroscienceInfection & Vaccines

Main therapy areas Opportunity-Driven

Protein engineeringBiologics Small

molecules Immuno-therapies Devices

Personalised healthcare capabilities

7

Evolving the business model to create maximum value from strong R&D productivity

Biotechs

Externalisation

Development

Manufacturing

Out-license Internal development g

CommercialisationPartner

Value creation through Internal development and Externalisation

8

Value creation through Internal development and Externalisation

R&D spend has shifted to support late-stage development

Pipeline progression driving faster shift towards late-stage development

TargetedR&D investment by stage (%)

40% 47%Late-stage

development Late-stage development

2013 – 2016 Plan*

44% 53% 57%

38%32%

Early development Early

development

33%28% 26%

57%

22% 21%Discovery

20162013 2014 2013 2015

Discovery

development

22% 19% 17%

8% 26%

actualactual estimate

*2013-2016 plan as of March 2013

9

Growth platforms: Strong delivery

FY 2014 Growth (%)

$476m 70Brilinta

$1,870m 139Diabetes

$5 063m 10Respiratory $5,063m 10Respiratory

$5,827m 12Emerging Markets

$2,227m (3)* Japan

O l i i th th l tf

10

Oncology emerging as sixth growth platform*Including impact from mandated price cutsGrowth rates at constant exchange rates (CER)

2014: Targeted business development in main areas

NGMRespiratory, Inflammation Cardiovascular & Metabolic OncologyNGM& Autoimmunity Disease Oncology

• Strengthened diabetes portfolio and commitment to maintherapeutic areas

• Strengthened inhaled portfolio in asthma and COPD

SNG001 N l i h l d i t f St t i t hi /

Respiratory

therapeutic areas

• Myalept divestment reinforced focus on main strategic priorities; allows for redeployment of resources

• SNG001: Novel, inhaled interferon beta in clinical development for severe asthma

• Strategic partnerships / acquisitions strengthened oncology portfolio, particularly immuno-oncology-combination therapies, novel predictive biomarkers

PearlTriple combinationLABA/LAMA/ICS

11

Cambridge Biomedical Campus: A vibrant innovation hub

New UK R&D Centre and Global Corporate Headquarters

Future site ofPapworth Hospital

Addenbrooke’s HospitalThe Rosie Hospital

Laboratory of Molecular Biology

Cambridge InstituteSchool of Clinical Medicine

12

AstraZeneca: A biopharmaceuticals leader

Science-based biopharmaceuticals leaderin 3 main therapy areas

Productive R&D Strong business Sustainable organisation

Stable business of established products

Gl b l l i

Innovative, entrepreneurial culture

St t l t b

Platform of small molecules & biologics

S t i bl d l &

Productive R&D Strong business Sustainable organisation

Global scale; emerging market strength

6 platforms driving growth towards a balance of primary

Strong talent base

Simple and productive organisation

Sustainable model & early pipeline

Growing late-stage; strength in IO*

balance of primaryand specialty care

Disciplined capital allocation Commitment to progressive dividend

Growing focus on devices & diagnostics

p p p g

13

* IO = Immuno-oncology

Business overview

Current business is led by main therapy areas

Sales FY 2014Infection, Neuroscience, Gastrointestinal

31%

Oncology

RIA

12%

31%

RIA

CVMD 69%

19%

38%

Note:RIA: Respiratory, Inflammation & AutoimmunityCVMD: Cardiovascular & Metabolic Disease

15

Broad geographical presence; Emerging Markets strength

US39% of sales

Europe25% of sales

Japan

China9% of sales

p9% of sales

Rest of World Established(ex-Japan)5% of sales

Emerging Markets (ex-China)

14% of sales

%

Note: Sales FY 2014

16

Increasing importance of specialty care

Primary care vs. specialty care sales over time

Future

Now

Primary Care Specialty Care

17

Respiratory, Inflammation & Autoimmunity (RIA)

Respiratory:Unique position in bringing leading medicines to patients

Large & small molecules with compelling science

Diversity in formulation to enable unique combinations

Leading devices & choice for patients

19

Respiratory:Unmet need remains in asthma and COPD

Asthma COPDActive patients, millions, 2014 GOLD-defined patients, millions, 2014

GINA step GOLD stage

1-3

4-5 1.8m severe, inadequately

controlled despite compliance

1.8m severe, inadequately


60

4438

GINA step

1-2

3-4 1.6m severe, inadequately


1.6m severe, inadequately


44

GOLD stage

38

11

2419

9

Ast

hma

prev

alen

ce

Dia

gnos

ed

Trea

ted

oor c

ontr

ol

CO

PDpr

eval

ence

Dia

gnos

ed

Trea

ted

oor c

ontr

ol

P P o

Note: G7 markets = US, France, Germany, Italy, Spain, UK, JapanSource: Decision Resources; Adelphi DSP 2012; other

20

COPD:Affects ~300 million* people; highest prevalence in developing countries

Male smoking prevalence trends by region (2011)

Lifetime male smoking prevalence:

50 59 9%60% and above

No Data

20-29.9%30-39.9%

50-59.9%40-49.9%

Below 20%

* Global estimate of diagnosed and undiagnosed patientsSource: Decision Resources; Adelphi DSP 2012; AZ internal analysis of G8 and ROW uplift

No Data

21

Symbicort:Resilience driven by devices

Negative impact of switch is well documented*

Device has a very strong impact on prescription decision**,***

57-69% of healthcare providers rate device asChange in SABA Successful treatmentP ti ll f l t t t

32%

57 69% of healthcare providers rate device as having very significant impactdosePartially successful treatment

Unsuccessful treatment

19.734.3

Mean 95%

0.40

0.20

s (%

)

100

80

2% 4%6%

9%

23%

13% 11%

50 7

29.6

27.8

CI change in S

AB

A

0.20

0.10

0

ropo

rtion

of p

atie

nts

40

60

0% 0% 2%

1 2 3 4 5 6 7 8 9 10

Healthcare providers switch device typically in <10% of consultations

50.737.9

A daily dose

-0.10

Switch (n=824)

Pr

0

20

Non-switch (n=824)

-0.20

• Thomas M, Price D, Chrystyn H, et al. Inhaled corticosteroids for asthma: Impact of practice level device switching on asthma control. BMC Pulm Med 2009; 9: 1.** Qual MR ; 70 HCP and 149 Patient Depth Interviews; Chn, Jpn, Ge, Sp & USA; Q1 2014 Fast Forward Research*** Quant MR; 882 Physician On-line survey; Chn Jpn, Ge, Sp & USA; Q1 2014 IPSOS

22

COPD: Inhaled portfolio addresses all disease severities and provides device choice

LABA/ICS LAMA/LABA/ICS

Increased risk

Adapted from GOLD

guidelinesDiagnosed with exacerbation

LAMA LAMA/LABA

Increased risk of exacerbation

Diagnosed with symptoms

Symptoms worsening

“Passive” dry powder inhaler, DPI, most commonly used

”Active” device, pMDI, preferred for elderly and for severe disease

LAMA/LABA/ICS+ PT010 PT009

PT003PT001

23

Asthma: Inhaled portfolio addresses all GINA steps and provides device choice

LAMA/ICS LAMA/LABA/ICSAdapted from

GINA guidelines

LABA/ICS

ICS

’As Needed’

GINA* classification

“Passive” dry powder inhaler, DPI, most commonly used

”Active” device, pMDI, preferred for young, elderly and for severe disease

1 2 3 4 5

y

’As Needed’

LAMA/ICS PT010LAMA/ICS+

PT009

PT008 - budesonide

24* GINA: Global Initiative for Asthma

Severe asthma: Targeting distinct patient subsets

HighTh2 driven | EOS low Th2 driven | EOS dominant

tinle

vel

Anti-IL-5Anti-IL-13

Anti-IL-13

B 20% A 35%

Th2 low | EOS highTh2 low | EOS low

Seru

m p

erio

st

CD

Low

S CD

Anti-IL-5

30% 15%

Blood eosinophil levelLow

Low

High

25

Benralizumab (severe asthma):Only IL5 receptor mAb in Phase III

Phase IIb data Exacerbation rate reduction

rbat

ion

rate

ve

to p

lace

bo

• Potent reduction in eosinophils

Ann

ual e

xace

red

uctio

n re

lativ

• Reduction in asthma exacerbation

• Improvement in lung

Baseline blood eosinophil count cutoff (cells per μL)

Are• Improvement in lung

function

Regulatory submission expected 2016

Source: M. Castro et al., Lancet Resp Med, 2014

26

Benralizumab (COPD): First mAb to show eosinophilic inflammation reduction

Mean change from baseline in FEV1 over time (per-protocol population)Phase IIa data

• First anti-IL5 / IL5R to

P = 0.014

demonstrate lung function improvement

• Primary endpoint not achieved, but trend toward reduction of exacerbations with elevated eosinophils

• Improvement in symptom scores

Phase III on track for completion 2018

Source: Brightling et al., Lancet Resp Med, 2014

Phase III on track for completion 2018

27

Tralokinumab (severe asthma):Targeting IL13, a central TH2 cytokine

Periostin-

AER for tralokinumab 300 mg Q2W vs placebo over 52 weeksPhase IIb data

• Identified potential responder population

0%

20%

40%

7%

32%(273, -53)

(886 88)

low (15)DPP-4 low (8)

• Identified promising biomarkers

• Efficacy across AER FEV1-60%

-40%

-20%

-44%-57%

(22,-74)

(-2, -89)

(886, -88)

(30,-86)

All (33)• Efficacy across AER, FEV1, ACQ-6 and AQLQ in subgroups

-80% -67%5 %All (33)

Periostin-high (18)

DPP-4 high (24)

Phase III on track for completion 2017Ph II i i IPF

AER – Asthma Exacerbation Rate, FEV1 – Forced Expiratory Volume in 1 second, ACQ-6 – Asthma Control Questionnaire,AQLQ – Asthma Quality of Life Questionnaire

Phase II ongoing in IPF

28

Inflammation & Autoimmunity:Strategy

Progressing pipeline of first-in-class, best-in-class medicines

Rheumatology Dermatology Gastrointestinal

• Gout

• Lupus

• Co-development with Amgen

P i i d

• Co-development with Amgen

C h ’ di• Rheumatoid

arthritis

• Psoriasis and psoriatic arthritis

• Crohn’s disease

• Ulcerative colitis

29

Inflammation & Autoimmunity:Significant growth potential

Global markets for rheumatoid arthritis, psoriasis, psoriatic arthritis, lupus, ulcerative colitis, Crohn’s disease and gout

$bn

40

50

60$bn

$50bn

20

30

40$30bn

0

10

Now Future

Source: IMS, biologic and novel oral brand sales by indication; Decision Resources

RA PsO&PsA Lupus UC&CD Gout

30

Lesinurad (gout):Regulatory submissions completed in US and EU

CLEAR 1 and CLEAR 2: Proportion of patients achieving

serum uric acid <6 mg/dL at Month 6 – NRILesinurad in gout

• Gout affects ~15m patients

• Potential to cause bone, joint, kidney damage and associated with CV disease and its co-morbidities

28%23%

54% 55%

30%40%50%60%

• Xanthine oxidase (XO) inhibitors act to control production of uric acid

• 40–70% of patients are not at goal on XO inhibitors alone

0%10%20%

CLEAR 1 CLEAR 2PBO + Allo LESU200 + Alloinhibitors alone

• Lesinurad and RDEA3170 increase excretion of uric acid

• RDEA3170 Ph II studies progressing with focus

PBO + Allo LESU200 + Allo

− AE profile, incl. renal AE of lesinurad200mg+allopurinol comparable to allopurinol alone

− Increases in serum creatinine observed lesinuradin monotherapy and fixed dose combination

Increases in serum creatinine observed lesinurad 200mg plus allopurinol vs. allopurinol alone (5.9-6.0% vs. 1.0-3.4%, >1.5x increase vs. baseline)

31

RDEA3170 (URAT1)Treatment for hyperuricemia and gout

Favorable sUA reduction in both monotherapyand combination therapy

• Potency provides impressive sUA reduction at

Highly potent Selective Uric Acid Reabsorption inhibitor (SURI)

• Potency provides impressive sUA reduction atlow doses

• Currently being developed as a monotherapy in Asia for broader indication of hyperuricemia and gout • Significant commercial opportunity in Asia, second g pp y ,

only to US market• Excretion pathway is an established approach in

clinical practice in Asia• Phase II development as combination therapy

f b d i di i f h i i dtreatment for broader indication of hyperuricemia and gout globally now underway

Source: Phase 1 study 3170-105: sUA Lowering Effect in Healthy Volunteers following Multiple Dosesof RDEA3170 or FBX (Single or Combination Treatment)FBX: febuxostat32

Brodalumab (psoriasis, psoriatic arthritis, asthma):Unique receptor-targeting approach

IL-25IL-17AIL-17A/F

IL-17F

Psoriasis• Three Phase III studies; two with

H2H superiority study design vs.IL-25IL-17A IL 17F H2H superiority study design vs. Stelara (ustekinumab) and placebo

• All three Phase III studies achieved primary and key secondary endpoints; regulatory submission 2015

IL-17R alpha

Psoriatic arthritis• Phase III on track

Asthma

Targeting IL17 receptor and inhibiting signaling of multiple ligands

• Opportunity for lifecycle management• Currently in Phase II

In partnership with Amgen

33

Targeting IFNα / IFNαR in lupus

Sif li b* bi d di tl t A if l b** t ti b d tSifalimumab* binds directly toIFNα neutralising IFNα subtypes

Anifrolumab** targeting broader spectrum of interferons (IFNα, IFNβ, and IFNω)

IFNIFN‐‐ββ IFNIFN‐‐ωω

IFNIFN‐‐αα

IFNIFN ββ

Phase IIb lupus study validates interferon targeting: Primary and secondary endpoints achieved

Receptor-targeting potentially better efficacy: Greater PD suppression(70–90% vs. 30–40% for sifalimumab)

Anifrolumab Phase II presentation expected 2015Phase III start expected 2015

34In partnership with Amgen* Sifalimumab: MEDI-545** Anifrolumab: MEDI-546

Sifalimumab (lupus): Significant improvement in SLE responder index and organ specific meas rementsspecific measurements

Day 1Endpoint at day 365

SRI (4) SRI (6) SRI (8)

All-comers population

Placebo (%) (N=98 - 108) 45.4 37.4 24.5

1200 mg dose (%), (N=98 - 107) 59.8 53.3 41.8

Effect size (%) 14 4 15 9 17 3Effect size (%) 14.4 15.9 17.3

P-value* 0.031 0.016 0.008

Dx+ population

Placebo (%), (N=79 - 88) 42.0 33.3 20.3

Day 169

24.5% treatment difference in CLASI 4 response

1200 mg dose (%), (N=80 - 87) 57.5 51.7 41.3

Effect size (%) 15.4 18.4 21.0

P-value* 0.038 0.012 0.004

CLASI-4 response1200 mg dose vs placebo**SLE: Systemic lupus erythematosus

SRI(x) SLE Responder Index (x=reduction in SLEDAI required for response)*P-value < 0.098 is considered to be statistically significant for the final analysis after adjusting for the interim analysis using O’Brien-Fleming type Lan-DeMetsalpha spending function approach to control type I error rate at 0.1 for the primary endpoint**mITT Population with a CLASI Activity Score ≥10 at Baseline35

Mavrilimumab (RA):First-in-class anti-GM-CSFRα antibody

ACR efficacy responses at day 169

73.4

7080

Placebo (N=81)

•

• 45–74% of patients on

Phase IIb data

24.7

50.6

28.4

61.2

25.9

40.5

30 40 50 60 70

Sub

ject

s (%

)

Mav. 30mg (N=81)Mav. 100mg (N=85)Mav. 150mg (N=79)

panti-TNF fail to achievean ACR50

• Mavrilimumab inhibits macrophage activation

Ph IIb lt

12.33.7

12.3 10.6 13.9

0 10 20

SACR70ACR50ACR20

macrophage activation, differentiation and survival

Phase IIb results• Co-primary endpoints: DAS28, ACR20 highly significant• Significant benefit after one week• Significant improvements in patient-reported outcomes• No apparent safety signals• No apparent safety signals

Source: Clin Pharmacol Ther. 92(3):352-9, 2012

36

Cardiovascular & Metabolic Disease (CVMD)

Cardiovascular & Metabolic Disease (CVMD):Strategy

Reducing CV morbidity, mortality and organ damageby addressing multiple CV risk factors

Cardiovascular disease

Metabolic disease

Chronic kidney disease

CHD/ACS

Atheros-clerosis/dyslipi-daemia

Diabetes NASH Disease progression

Symptomatic treatment

Heart failure

RegenerationHeart β- cell Kidney y

CHD: Coronary heart diseaseACS: Acute coronary syndromeNASH: Non-alcoholic steatohepatitis

38

CVMD: An area of historical strength, and rapidly rebuilding for sustainability

Business DevelopmentDevelopment

2013• Rebuild of pipeline through business development:

Epanova, Fibrogen, NGM, Moderna

2014• BMS acquisition should consolidate our position in Diabetes• Forxiga & Bydureon Dual Chamber Pen launches

39

Diabetes:Significant T2D disease burden exists globally

Anticipated to grow to 590 million by 2035380 million people with diabetes worldwide

• 55% increase in prevalence• 55% increase in prevalence

• Lower T2D mortality

• Significant increase in E i M k tEmerging Markets

Source: International Diabetes Foundation Atlas 6 edition, International Diabetes federation 2013

40

Diabetes:Non-insulin diabetes market to continue endemic growth

Expected revenues for insulin and other diabetes products

47 3$bn

8.8

6.45.547.3

27.8

16 7

8.59.83.2

8.84.2

27.8

11.8 16.7

20222013

SGLT 2 InsulinDPP 4GLP 1Other SGLT-2 InsulinDPP-4GLP-1Other

Source: Decision Resources (2014), Type 2 Diabetes Therapy

41

Diabetes:Innovative portfolio spanning all non-insulin classes

DPP-4

Ora

ls

SGLT-2

FDC SGLT-2 / DPP-4 saxa-dapa

GLP-1

AmylinInje

ctab

les

analogueI

42

Diabetes: R&D commitment

201920182017201620152014 201920182017201620152014

Asia add-on to insulin

DECLARE cardiovascular outcomes

Type 1 diabetes

Japan add-on to insulin

saxa+dapa+metvs dapa+met

saxa+dapa+metvs saxa+met

saxa/dapa vs sitagliptinsaxa/dapa

saxa/dapa vs SU

China add-on to insulin

China initial combination

DURATION NEO 1 exenatide weekly vs BID

EXSCEL cardiovascular outcomes

DURATION 7 add-on to insulin

DURATION NEO-1

DURATION NEO-2 exenatide weekly vs sitagliptin

exenatide weekly vs BID

~40,000 patients in clinical trials world wide

exenatide+dapagliflozin

43

Diabetes: Potential of early combinations to slow disease progression

Illustrative

44

Oral combinations:Saxa/dapa & saxa/dapa/metformin

Portfolio well-positioned to enableearly combination treatment

Significant reduction in HbA1cwith low rates of hypoglycaemia

Adjusted mean change from baseline in HbA1c at 24 weeks

• Saxa/dapa added to metformin in poorly controlled T2DM

• HbA1c reduction 1.47%

• HbA1c <7% in 41% of patients

• Saxa/dapa regulatory submission: US in Q4 2014, EU expected in 2015

• Saxa/dapa/met FDC development ongoing. Regulatory submission expected post 2016

a Number of randomized patients with non-missing baseline values and Week 24 values.

CI fid i t l

Rosenstock J, Hansen L, Zee P, Li Y, Cook W, Hirshberg B, Iqbal N. Dual Add-On Therapy in Poorly Controlled Type 2 Diabetes on Metformin: Randomized Double-Blind Trial of Saxagliptin+Dapagliflozin vs Saxagliptin and Dapagliflozin Alone. 127-LB, American Diabetes Association, 2014.

CI, confidence interval.

45

Farxiga / Forxiga & Xigduo:Insulin doses remained stable over 2 years

Add-on to Insulin, 90-006

• Dapagliflozin showedsustained reductions in HbA1c in when used inHbA1c in when used in combination with insulin

• Patients on dapa +insulin lost weight

• -3kg vs insulin alone

• Insulin doses remained• Insulin doses remained stable over the study period

Farxiga / Forxiga + insulin maintained HbA1c and induced weight loss vs insulin aloneg g g

Ann Intern Med. 2012;156(6):405-415Study 006 Clinical Study Report, Figure4, Table 11.2.6.1.1.46

Brilinta:PLATO results displayed unique clinical profile

13

e in

cide

nts

(%)

3

4

5

6

7

5.1

4.0

Clopidogrel

Ticagrelor

Clopidogrel

Ticagrelor

11.79.8

CV death

e in

cide

nts

(%)

56789

10111213

Months after randomisation0 2 4 6 8 10 12

Cum

ulat

ive

0

1

2 HR=0.79; 95% CI=0.69–0.91; p=0.001(HR, 0.84; 95% CI, 0.77–0.92; P<0.001)

0 2 4 6 8 10

12

Cum

ulat

ive

01234

Months after randomisationNo. at risk

• Continuous benefit for one year• Mortality benefit

Ticagrelor 9333 8628 8460 8219 6743 5161 4147

Clopidogrel 9333 8521 8362 8124 6650 5096 4047

• Potential unique benefit beyond P2Y12 inhibition driven by ENT1K-M, Kaplan-MeierWallentin L, et al. presentation at ESC 2009

47

Brilinta:PARTHENON potentially transforms atherosclerosis treatment

2014 2015 2016 2017 2018 2019

H1 H2 H1 H2 H1 H2 H1 H2 H1 H2 H1 H2

;DataSubmission US/EMEA Japan China

DataSubmission USEMEA Japan China

Stroke/TIA

Prior MI

Data

Data

Submission

Submission

US

US

EMEA

EMEA

Japan

Japan

China

ChinaDiabetes

Peripheral Arterial Disease

OAP market access(% current volume) 20% 20% 31% 68% 83% 84%+

MI: myocardial infarctionTIA: transient ischaemic attackOAP: oral antiplatelet

48

PEGASUS study design

Positive topline data announced Q1 2015 filing planned 2015Positive topline data announced Q1 2015, filing planned 2015

Patients who had a MI within 1–3 years AND have at least one additional atherothrombosisrisk factor (n=21 000)risk factor (n=21,000)

Ticagrelor 60 mg BID+ 75 150 mg ASA

Placebo+ 75 150 mg ASA

Ticagrelor 90 mg BID+ 75 150 mg ASA+ 75–150 mg ASA

>12<44 months follow up

+ 75–150 mg ASA+ 75–150 mg ASA

(quarterly in Year 1, then semi-annually)

Primary efficacy endpoint: CV death, MI or stroke P i f t d i t TIMI j bl di

49

Primary safety endpoint: TIMI major bleeding

Epanova (prescription grade Omega-3 free fatty acid EPA+DHA)Confident in clinical trial programme & unique profileA global opportunity to manage dyslipidemia,a significant unmet medical need

• Unique formulation with greater bioavailability than other omega-3s, independent of pancreatic lipase

CV risk increases dramatically as triglyceride levels increase

Severe HTG is associated with an increased risk for complications, including:1,3-10g p p p

• Unique dosing regimen - two-to-four capsules once daily with or without food

• Combined, the US, EU5 and Japan have ~28M patients with uncontrolled triglycerides

p g• CVD• diabetes• pancreatitis• renal disease

15 CV risk (CHD odds ratio)patients with uncontrolled triglycerides.

• Strong phase III clinical program with EVOLVE1 ; ESPRIT2 and a large-scale CV outcomes trial (STRENGTH) in combination with a statin in patients with mixed dyslipidaemia.

11.0

5

10

( )

• Approved in US 5 May 20143.0

2.01.01.01.0

0

Triglycerides (mg/dL)500–799300–499200–299150–199100–149<100

Source: Hopkins PN et al J Am Coll Cardiol 2005;45:1003–1012[1] Christian et al. Am J Cardiol. 2011;107(6):891-897; [2] Ford et al. Arch Intern Med. 2009;169(6):572-578; [3] Deng et al. World J Gastroenterol. 2008;14(28):4558-4561; [4] Nichols et al. Am J Cardiol. 2011;107(2):225-229; [5] Hopkins et al. J Am Coll Cardiol. 2005;45(7):1003-1012; [6] Valdivielso et al. Atherosclerosis. 2009;207(2):573-578; [7] Ascasoet al. Eur J Intern Med. 2011;22(2):177-181; [8] Lloret Linares et al. Pancreas. 2008;37(1):13-18; [9] Sandhu et al. Lipids Health Dis. 2011;10:157; [10] Lee et al. Am J Med Sci. 2009;338(3):185-189.

Source: Hopkins PN, et al. J Am Coll Cardiol. 2005;45:1003 1012

1. EVOLVE: 12-week randomized, double-blind placebo controlled trial in very high triglyceride population (≥500mg/dL)

2. ESPRIT: 6-week randomized, double-blind placebo controlled trial in mixed dyslipidemia. High CV risk patients with TG 200 to <500 mg/dL on baseline statin therapy

50

Roxadustat/FG-4592 (HIF-PH inhibitor) Anaemia treatment beyond the boundaries of current rEPO therapy

Stimulates erythropoiesis without need for concomitant iron treatment

• Potential first HIF-PH inhibitor with filing in 2016 (China) and 2018 (US)

Potential first in class oral HIF-PH inhibitor for CKD & ESRD

(China) and 2018 (US)

• Two AZ Phase III studies commenced enrolment in June 2014 – one in Chronic Kidney Disease (CKD) patients not on dialysis and one in End Stage Renal Disease (ESRD) patients on dialysisDisease (ESRD) patients on dialysis

• Roxadustat is in development for use in anaemia of CKD and ESRD

• High unmet need for oral agent with• High unmet need for oral agent withimproved safety profile

51

Tenapanor/AZD1722 (NHE3 inhibitor)Treatment of hyperphosphatemia & progression of renal disease

Significantly prevented the calcification of the aorta in a pre-clinical model

Reduces sodium and phosphate absorption from the gut

AZD1722

Sodium

• Excessive sodium and phosphate are important renal and cardiovascular risk factors for patients with renal diseaseSod u

NHE3 T t

disease

• Clinical data show clinically meaningful effects on sodiumand phosphate

Transporters• Pre-clinical data show that

tenapanor/AZD1722 prevents vascular damage

Vehicle AZD1722Phosphorus

Vehicle AZD1722Calcium

52

Oncology

Oncology:Legacy

$$m

5000

6000

4000

Arimidex

2000

3000

NolvadexZoladex

Arimidex

IressaFaslodex

Other

0

1000

Nolvadex

Casodex

54

01998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014

Oncology:Cancer incidence a global healthcare challenge

Breast cancer treated patients

• Over 8.2m adults die each year from cancer 600,000

800,000

• Over 13m people are predicted to die from cancer in 2030

0

200,000

400,000

2015 2025US EU5 JP CN

800,000

1,000,000

1,200,000

60,000

80,000

100,000

NSCLC 1L treated patients Ovarian cancer 1L treated patients

0

200,000

400,000

600,000

2015 2025US EU5 JP CN

0

20,000

40,000

,

2015 2025US EU5 JP CN

Source: NSCLC: Kantar Health Patient Metrics (US, UK, Spain, Italy), AZ internal sources (France, Germany, Japan and China)Breast: Kantar Health Patient Metrics (US, EU5, Japan), AZ internal sources (China)Ovarian: Kantar Health Patient Metrics (US, EU5, Japan); Decision Resources (China, Urban)Global Incidence and Mortality Numbers: Globocan 2012 (IARC) Projection. Population forecasts taken from UN, World Populations Prospects (2012 revision) Forecast market size Decision Resources Pharmaview

55

AstraZeneca Oncology

Bold ambition

By 2020, we will be a recognised

Common vision

Redefine cancer treatment paradigmleader in oncology, delivering6 new medicines to patients

Restore patients’ lives Eliminate cancer as cause of death

4 key MoA & platforms 4 main disease areas

Combinations

Personalised healthcare

Smart development crucial to leadership

56

Oncology:Combine therapies to change treatment paradigm

Combination therapies may enhance efficacy by:

PD-L1 + CTLA-4

1.5

Control

TORC1/2 + Faslodex

• Targeting complementary pathways

• Establishing synergistic effectstum

ourv

olum

e (m

m3 )

0.5

1Faslodex

AZD2014

AZD2014+FaslodexTu

mou

r vol

ume

(cm

3 )

• Overcoming resistance to monotherapy

• Improving risk / benefit profile

Study days0 10 20

Study days

OX40 + CTLA-4

• Improving risk / benefit profile

tum

ourv

olum

e (m

m3 )

Study days

57Preclinical models

Oncology:Smart development crucial to leadership

Potential filing <2½ years from first dose in manAZD9291

Leapfrog competition into early line of therapy MEDI4736 (PD-L1)PACIFIC study

First in ctDNA diagnostic testing

y

Iressa / AZD9291

MEDI4736BRAF / MEK Good combinability enables novel triplet combination

58

Scientific leadership:Four key platforms

• MEDI4736 (PD-L1)

• Tremelimumab (CTLA-4)

Immunotherapy

• AZD9291 (EGFRm)

• Selumetinib (MEK)

Tumour driversand resistance

• Olaparib (PARP)

• Cediranib (VEGF)**

DNA damage repair

• Moxetumomab (CD22)

• ADC-Spirogen*

Antibody drug conjugates

• MEDI0680 (PD-1)

• MEDI6469 (murine OX40)

• MEDI6383 (OX40 Fusion Protein)

• MEDI0562 (OX40 humanisedmAb)

• AZD2014 (TORC1/2)

• AZD4547 (FGFR)

• AZD5363 (AKT)

• AZD6094 (cMET)

• AZD8186 (PI3Kβ)

• AZD1775 (Wee1)

• AZD6738 (ATR)

• AZD0156 (ATM)*

• AZD2811 (AKB)*

• ADC-Bispecific*

• AZD9150 (STAT3)

• AZD5069 (CXCR2)

• AZD8186 (PI3Kβ)

• AZD8835 (PI3Kα)

• MEDI0639 (aDLL4)

• MEDI-573 (aIGF1/2)

• AZD9496 (SERD)

• AZD5312 (AR antisense)

* Preclinical** Combination with DDR

59

Scientific leadership:Tumour drivers & resistance


• Highly altered signallingHighly altered signalling pathways in cancer

• Interconnected pathways allow resistance / escapeallow resistance / escape mechanisms

• Multiple targets identified as potential tumour driver mutations

Tumour

60


AZD9291:EGFR mutant selective inhibitor in lung cancer

• Potentially first irreversible selective inhibitor of double

Strong evidence of monotherapy activity

EGFR mutations

• Awarded FDA Breakthrough Therapy Designation

Best percentage change from baseline in target lesion*

• FSI 1st line Phase III Q4 2014, data expected 2017

• Combinations with MEDI4736 (PD L1) MET (cMET) and(PD-L1), MET (cMET) and selumetinib (MEK) ongoing (FSI Q3 2014)

US NDA submission expected Q2 2015 in NSCLC 2L* ESMO 2014

61

AZD9291: Early efficacy in 1st line EGFRm NSCLC


Preliminary evidence of activity in NSCLC brain mets1st line EGFRm

AA

Overall disease control rate (CR+PR+SD) = 95%A)

A)

B)

A)

B)

Clinical activity of AZD9291 in brain mets has been observed in a Phase I study in patients with acquired resistance to current EGFR-TKIs.

FLAURA Ph III NSCLC 1L EGFR H2H 1 t TKI t t Q1 2015FLAURA: Phase III NSCLC 1L EGFRm H2H vs 1st gen. TKI start Q1 2015

62

AZD2014:Dual TORC1/2 inhibitor


B d t ti l i b t l

Strong evidence of activity Differentiated clinical activity

Dual TORC1/2 + paclitaxel* • Broad potential in breast, lung, ovarian cancer and lymphoma

• Dual TORC1/2 and intermittent

Dual TORC1/2 + paclitaxel

Dual TORC1/2 and intermittent weekly dosing schedule to deliver better efficacy and tolerability

25 mg 3/7

• Potential accelerated Phase III investment decision in 2015

50 mg 3/7

75 mg 3/7

100 mg 2/7

75 mg 2/7

Combination with Faslodex in ER+ breast cancer to be submitted for

*Basu et al ESMO 2014

Combination with Faslodex in ER+ breast cancer to be submitted for presentation in 2015

63

AZD6094:Potent, selective cMET inhibitor of MET-driven tumours


Activity in MET-driven papillary renal cell cancer (PRCC)

• Active in MET amplified and MET- mutant settings

hang

e fro

m b

asel

ine

(%)

• First-in-class opportunity in papillary renal cell cancer (PRCC)

• Phase II trial in PRCC ongoing

est t

umou

rass

essm

ent c

h g g

• Phase II trial in MET-amplified gastric and lung cancer ongoing

Be

• Combination with AZD9291 in2nd line EGFR mutant lungcancer ongoing

In partnership with Hutchison Medi PharmaGan et al ASCO 2014

64

AZD9496:Oral selective estrogen receptor degrader (SERD)


Undosed ControlsPEG/C ti l hi l

Greater tumour inhibition than Faslodex

• Improved potency and bioavailability allows greater

1 2

1.4

1.6

1.8

2.0

ume

(cm

3 )

PEG/Captisol vehicle Peanut oil vehicle Faslodex 5 mg x3 weekly s.c. Tamoxifen 10 mg/kg p.o. once daily Oral SERD 5 mg/kg p.o. once daily

Undosed control + vehicles

Tamoxifen

bioavailability allows greater estrogen receptor (ER) knockdown

• Oral formulation

0.4

0.6

0.8

1.0

1.2

Mea

n Tu

mou

r Vol

Faslodex

AZD9496

• Clinical development started Q4 2014

Ph l i l d t b itt d0 20 40 60 80 100 120

0.2

Days of Dosing

• Pharmacological data submittedfor AACR 2015

65

DNA Damage Repair (DDR): Targeting the Achilles heel of cancer

• Highly altered pathways in cancer

• Traditional chemotherapies depend on DDR pathways

• Most extensive portfolio of DDR agents in the industry

66

Lynparza (olaparib): First-in-class PARP inhibitor

• BRCAm ovarian cancer: SOLO-2 (2015*)Olaparib, n=74 Placebo, n=62

Clinical benefit in BRCAmovarian cancer

Ongoing Phase III programmes

• BRCAm ovarian cancer: SOLO-2 (2015 ), SOLO-1 (2016*)

• BRCAm breast cancer: OlympiAD (2016*)

• Gastric cancer: GOLD (2017*)gres

sion

-free

1.0

0.9

0.8

0.7

Median 11.2 mo 4.3 moHR=0.18 95% CI (0.10, 0.31); P<0.00001

Gastric cancer: GOLD (2017 )

• BRCAm pancreatic cancer:POLO (FSI Q4 2014)

• Promising activity in late-stage prostatetion

of p

atie

nts

prog 0.6

0.5

0.4

0.3

0.2 Olaparib BRCAm Promising activity in late stage prostate cancer (10/30 RR, ESMO 2014)

Pro

port

00

3 6 9 12 15

0.1 Placebo BRCAm

Months

A d i US d EU Q4 2014Approved in US and EU Q4 2014

*Data available

67

AZD1775:Wee1 inhibitor; encouraging data in ovarian cancer

DNA damage repair

Wee1: Role in cell cycle progression and DNA damage checkpoints

Platinum-sensitive relapsed ovarian cancer

11/14 RECISTG2/Mcheckpoint

• 11/14 RECIST responses

• PFS 10.8 months

• 13/14 GCIG responses

Wee113/14 GCIG responses (includes CA125 responses)

• Phase II study in ovarian; Lynparza combination due to

G1/Scheckpoint

S phasecheckpoint

y pstart Q1 2015

• Phase I/II trials in NSCLC

Phase III ovarian cancer investment decision expected 2015

68

AZD2811:Aurora Kinase B inhibitor (AKBi): AML proof of concept

DNA damage repair

• Novel mechanism of action:

Phase II: AKBi vs low-dose cytarabine(LDAC) in elderly unfit AML

Differentiated profile

AKBi vs LDAC • Novel mechanism of action: Regulates mitosis and chromosomal segregation

• Nanoparticle formulation inAKBi 1200mg (n=48)LDAC 400

OCRR (+Cheson) +30%

Overall Survival (HR) 0.88 (0.49-1.58)

• Nanoparticle formulation in development*

• Potential in DLBCL and AML

Ove

rall

Sur

viva

l LDAC 400mg (n=26)

• Plan to discuss further steps with regulators early in 2015

Kantarjian et al Cancer 2013;119:2611-19* In collaboration with BIND Therapeutics

69

Immuno-oncology (IO):Changing the treatment paradigms for cancer

A ff ti i• An effective immune responseis durable - possibly life-long

• Cancer hijacks many immune pathways to escape destructionpathways to escape destruction

• Our robust pipeline allows identification of combinations that restore the immune responserestore the immune response

70

Immuno-oncology (IO):Three major components to cancer immune response Immunotherapy

2. Optimizing T cell function and memory

PD-L1

PD-1 CTLA-4

OX40

NME-4 NME-5

1. Antigenpresentation

3. Inhibition bymicroenvironment

HPV V i * IDO* CXCR2AZD9291HPV Vaccine* IDO*

CCR4* STAT3

CXCR2

Radiotherapy

AZD9291

Iressa

BRAF/MEK*

NME-1

NME-2 NME-3

NME-6 NME-7

NME-8

• Clinical collaborations• Note: Update as of 18 November 2014

NME 2 NME 3

PreclinicalClinical71

MEDI4736 (PD-L1):Triplet w/dabrafenib and trametinib in BRAFm melanoma Immunotherapy

Potential for well-tolerated, durable benefit in BRAFm melanoma

Increase in CD8 Tumour Infiltrated Lymphocytes (TILs)

BRAFi/MEKi treatment effect

• Clinical data for BRAFi/MEKiprovide rationale for “triplet” combination

• Potential for durable response in• Potential for durable response in 1L BRAFm melanoma patients

• Phase I “triplet” combination well tolerated at full monotherapy

Increase in PD-L1 expression

tolerated at full monotherapy doses; MTD not reached

Frederick et al, 2013

In collaboration with GSK

Presentation of Phase I “triplet” combination planned for H1 2015

72

MEDI6383 (OX40): Pathway drives potent, durable anti-tumour T cell immunity

-‐50

0

50

100 PD on day 56 SD on day 56+

Stimulatory activity in periphery

Murine OX40: Phase I evidence of activity

• Murine anti-human OX40 (active in monotherapy; in combination with MEDI4736 now)

• Human OX40L fusion protein (currently in dose escalation)

• OX40 (FSI Q1 2015)

Best tumour assessment change from baseline (%)

3 unique OX40 molecules with distinctive biology

Immunotherapy

73

AZD9150: STAT3 and roles in tumour microenvironment Immunotherapy

STAT3 inhibition decreases immune tolerance in tumour microenvironment

Durable responses in Phase I monotherapy studies

Phase I presented at EORTC Nov 2014Nature Reviews Immunology 7, 41-51 A CR and PRs lasting > 1year in lymphoma and liver cancer studies

Phase I presented at EORTC Nov 2014STAT3 + MEDI4736 Phase I study start H1 2015

74

AZD5069:CXCR2 affects myeloid-derived suppressor cell trafficking Immunotherapy

• First-in-class CXCR2 antagonist in oncology

• Potential synergistic activity with MEDI4736 (PD-L1)

• Phase I combination study of CXCR2 + MEDI4736 (PD-L1) ( )expected to start in H1 2015

75

Immuno-oncology (IO):Combinations address multiple immune pathways

PD-L1 EGFR T-cell activation combined with increased tumour visibility

PD-L1 MEK/BRAF T-cell activation combined with increased antigen presentation

PD L1 HPV V i T ll ti ti bi d ith i d i i

Antigen presentation

PD-L1 HPV Vaccine T-cell activation combined with increased priming

CTLA-4 PD-L1 Increased T-cell activation through blocking multiple inhibitory pathways

PD-1 PD-L1 Increased T-cell activation through complete blockade of the PD-1/PD-L1 axis

T-cell killing and memory

PD-L1 IDO T-cell activation combined with removal of inhibition

PD-1 PD-L1 Increased T-cell activation through complete blockade of the PD-1/PD-L1 axis

PD-L1/CTLA-4 OX40 Increasing T cell number, function and memory

Tumour microenvironment

PD-L1 CCR4 T-cell activation combined with T-reg depletion

PD-L1 CXCR2 T-cell activation combined with reduced MDSC suppression

PD-L1 STAT3 T-cell activation combined with myeloid reprogramming

Enables precise identification, location and relationship between multiple components of tumour microenvironment

76

Immuno-oncology (IO): Unique indications, novel combos, speed of execution Immunotherapy

LeadershipDifferentiationSpeed1 2 3

Quickest path to approval • Rapid program expansion• Adaptive decision-making• Patient selection

First or best-in-classagents

Monotherapy MEDI4736 (PD-L1)• Late-stage NSCLC• 2L head/neck (SCCHN)

Differentiated tumour types and biomarker subsets

Combinations• MEDI4736 (PD-L1) +

tremelimumab• MEDI4736 (PD-L1) +

MEDI4736 (PD-L1) / tremelimumab combo• Late-stage NSCLC• 2L head/neck (SCCHN)

High value leapfrog indications:• Stage 3 unresectable NSCLC• Adjuvant NSCLC

MEDI4736 (PD L1) + AZD9291

Three OX-40 antibodies• Murine, humanised, fusion• Monotherapy, combinationMonotherapy, combination

77

MEDI4736 (PD-L1):Monotherapy; early, durable activity in multiple tumours* Immunotherapy

Total study population(10 mg/kg q2w)

Ongoing responders

Total 92% (33/36)

RECIST response

PD L1+ 22% (18/81)PD-L1+ 22% (18/81)

PD-L1- 5% (12/233)

Total 10% (36/352)

Disease control rate at 12 weeksDisease control rate at 12 weeks

PD-L1+ 47% (38/81)

PD-L1- 28% (64/233)

T t l 33% (115/352)Time (weeks) Treatment stopped

2 k Total 33% (115/352)

* Patients with baseline and ≥1 on-treatment scan; disease assessment at 6 weeks, 12 weeks, 16 weeks, and then every 8 weeksData cut-off: 21 August, 2014

at 52 weeks

78

MEDI4736 (PD-L1) + tremelimumab:Encouraging efficacy for combination in NSCLC Immunotherapy

Best change in tumour size by dose cohort (n=18)

Tumour shrinkage by dose cohort (n=18)

All patients ORR Stable disease

MEDI4736+tremelimumab 28% (5/18) 28% (5/18)

79

MEDI4736 (PD-L1) + tremelimumab:Potentially better response in PD-L1 negative tumours Immunotherapy

PD-L1 negative patients in NSCLC

MEDI4736 (PD-L1)

MEDI4736 (PD-L1) + tremelimumab

70%(7/10)

42%

*

**

42%(31/74)

30%(3/10)

ORR ORR + SD

10%(7/74)

ORR ORR + SD

* Mono: ORR 10% (7/74), 95%CI (3.9%, 18.5%) SD≥12weeks 32.4% (24/74), 95%CI (22.0%, 44.3%) ** Combination: ORR 30% (3/10), 95%CI (6.7%, 65.2%) SD≥12weeks 40% (4/10), 95%CI (12.2%, 73.8%)

80

MEDI4736 (PD-L1):Development in NSCLC Immunotherapy

ATLANTIC ARCTIC ADJUVANTPACIFIC

Fast-to-market monotherapy First-mover advantageEarly NSCLC

ATLANTICPhase II

3L NSCLCPD-L1 positive

ARCTICPhase III

3L NSCLC

ADJUVANT Phase III

Adjuvant NSCLCPD-L1 positiveand unselected

PACIFICPhase III

Stage 3 unresectableNSCLC

MEDI4736 (PD-L1) monotherapy

Single-arm Phase II

MEDI4736 (PD-L1) monotherapy; treme

combination (PD-L1 neg)

Randomised vs. SOC*


Randomised vs. SOC*


Randomised vs. SOC*

Data: 2015 Data: 2017 Data: 2020Data: 2017

Phase III MEDI4736 (PD-L1) + tremelimumab underway

*SOC = standard of care

Phase III MEDI4736 (PD L1) + tremelimumab underway

81

Non-small cell lung cancer (NSCLC):Focus on medical need in PD-L1 negative disease Immunotherapy

PD-L1 negative NSCLCMutation status

KRAS/EGFR/ALK WT KRASm EGFRm ALKm

• Largest segment of NSCLC

• Not addressed byatus

87k pts 21kpts

PDL1Dx+ 24k pts

• Not addressed bymarketed targetedtherapies (EGFR, ALK)

• Significant unmet medical

PD

-L1

sta

130k pts 35k pts 31kt

PDL1Dx • Significant unmet medical

need remains 130k pts 35k pts ptsDx−

EGFRm 16%; KRASm 18%; ALKm 3%; EGFR/ALK/KRAS wt 63% (Kantar and AZ estimates 2020)

82

MEDI4736 (PD-L1):Head and neck cancer (SCCHN) Immunotherapy

After two MEDI4736 (PD-L1) infusions (30 days)

Before MEDI4736 (PD-L1) infusion

96 year old patient who had progressed on cetuximab prior to study entry (HPV negative, PD-L1 positive)

SCCHN=Squamous cell carcinoma of head and neck

83

MEDI4736 (PD-L1):Head and neck cancer development Immunotherapy

HAWK CONDOR EAGLE

Fast-to-market monotherapy

First-mover advantagecombination therapy

HAWKPhase II

Platinum failuresPD-L1 positive

CONDORPhase II

Platinum failuresPD-L1 negative

EAGLE Phase III

Platinum failuresUnselected


Single-arm Phase II


Contribution ofcomponent study


Randomised study vs. SOC

Data: 2015 Data: 2016 Data: 2017

Phase III monotherapy and combination with tremelimumab to start early 2015

84

Immuno-oncology (IO): 13 ongoing, 6 planned combinations to address multiple immune pathways Immunotherapy

PD-L1 Ph III NSCLC

tremelimumab Ph III Mesothelioma

S AZD9291/ l ti ib

PD-L1 + tremelimumab Ph III 3L NSCLC

PD-L1 +/- tremelimumab Ph I/II/III SCCHN

PD L1 +/ t li b Ph I/II S lid t

Planned studiesOngoing studies

Seq. AZD9291/selumetinib + docetaxel/Iressa/CTLA-4 & PD-L1 Ph II NSCLC

PD-L1 Ph II Solid tumours

PD-L1 Ph II SCCHN

PD-L1 + mOX40 Ph I/II Solid tumours

PD-L1 +/- tremelimumab Ph I/II Solid tumours

mOX40 + rituximab Ph I/II Haematological

CD19 + PD-1 Ph I/II Haematological

PD-L1 + STAT3 Ph I/II Solid/haem tumours

PD-L1 + CXCR2i Ph I/II Solid tumoursPD-L1 Ph I/II MDS

PD-L1 + tremelimumab Ph I NSCLC

PD-L1 + tremelimumab Ph I Solid tumours

PD-L1 + BRAFi + MEKiPD L1 + MEKi Ph I Melanoma

PD-L1 + CXCR2i Ph I/II Solid tumours

PD-L1 + INCB024360 (IDO1) Ph I/II Solid tumours

PD-L1 + mogamulizumab (CCR4) Ph I/II Solid tumours

tremelimumab + mogamulizumab (CCR4) Ph I/II Solid tumours

PD-L1 + ADXS-HPV Ph I/II HPV-cervical & H&NPD-L1 + MEKi

PD-L1 + Iressa Ph I EGFRm NSCLC

PD-L1 + PD-1 Ph I Solid & haems

PD-L1 + AZD9291 Ph I EGFR M+ NSCLC

tremelimumab + Iressa Ph I EGFRm NSCLC

mOX40 + tremelimumab Ph I/II Solid tumours

PD-L1 + ibrutinib (BTKi) Ph I/II Haematological

PD-L1 + radiation Ph I Solid tumours

PD-L1 + tremelimumab + radiation Ph I Solid tumourstremelimumab + Iressa Ph I EGFRm NSCLC

OX40 fusion protein Ph I Solid tumours PD-L1 + tremelimumab Ph I Haematological

OX40 Ph I Solid tumoursNew since ESMO 201485

Note: Update as of 18 November 2014

Infection, Neuroscience & Gastrointestinal (ING)

Movantik/Moventig (PAMORA)Potential first QD oral with a targeted mechanism of action for OIC

• Positive Phase lll data from KODIAC programme, tl bli h d i NEJM

Targeting patients with high unmet need Once a day oral, peripherally acting, μ-opioidreceptor antagonist

recently published in NEJM

• Only PAMORA with QD oral dosing

• Approved in US Q3 2014 and EU Q4 2014

• High unmet need with many patients not achieving desired treatment outcomes:

• Up to 81% of patients worldwide taking opioidsfor long-term pain develop opioid induced constipation (OIC)

O l 40 50% f th OIC ff hi i• Only 40-50% of these OIC sufferers achieving desired treatment outcomes with current options

• First mover advantage as an oral PAMORA therapy in OIC in patients with chronic pain, two other PAMORAs could launch within 18-24 months

Source: NektarThis programme is being developed in partnership with Nektar

87

CAZ-AVI (Ceftazidime - Avibactam)Novel combination effective against broader range of resistant Gram negati e pathogensGram-negative pathogensDifferentiated novel combination against broad range of resistant gram-negative pathogens

Increasing resistance to 3rd gen. cephalosporin is leading to a serious public health issue

• Treating hospitalised patients with intra-abdominal infections (cIAI), urinary tract infections (cUTI), hospital acquired pneumonia (HAP), including ventilator acquired pneumonia (VAP)

• Over 1M patients a year suffer from infections known• Over 1M patients a year suffer from infections known or suspected to be resistant to 3rd gen. Cephalosporins

• 1st regulatory filing 2015• Differentiated vs CXA-201 through KPC coverage g g

and broader ESBL-coverage, hence active against broader range of resistant gram-negative pathogens

• Actavis has commercialisation rights in N. America, AZ has rights ROW

Proportion of 3rd gen. cephalosporins (R) resistant Klebsiella pneumoniae

This programme is being developed in partnership with Forest Laboratories Source: ECDC/Dundas/TESSy, 2012

88

Proportion of 3 gen. cephalosporins (R) resistant Klebsiella pneumoniae

BACE (AZD3293)Highly potent inhibitor of the first step in Aβ peptide production

AZD3293 has demonstrated significant dose-dependent reduction in CSF A in Phase 11

• Alzheimer’s disease pathology is characterised by A peptide deposition

Highly promising approach to address unmet medical need in Alzheimer’s

ne)

A peptide deposition

• Disease causing mutations in APP directly linked to BACE activity

• Potential to slow disease progression in prodromald ild Al h i ’ di

Day

-1 B

asel

i

Placebo

and mild Alzheimer’s disease

• Future market for a successful BACE in at risk populations, expected to be aided by emerging diagnostics

Aβ1

-42

(% o

f

15 mg AZD3293*

50 mg AZD3293*

• Registrational Phase II/III trial started Q4 2014

• Alliance with Eli Lilly for the development and commercialization of AZD3293

CS

F

Time (hr)

* QD regimen at steady state

1 Budd-Haeberlein S. et al (2013) AZD3293 a novel BACE1 inhibitor: Effect on plasma and CSF Abeta peptides following single and multiple-dose administration. Journal of Nutrition, Health, and Aging, Issue 9, Vol 17. 89

Emerging Markets/Japan

Emerging Markets – A platform for success

fastest growing MNC pharmaplayer across Emerging Markets

3rd

China~$2 2bn

~$5.8bn sales in Emerging Markets

~$2.2bn

91Source: Internal 2014 Ex Factory Sales / IMS Health. Copyright 2014. All Rights Reserved.

Emerging Markets: Continued strong growth

China19%

21%23%22%21%

13%

21%21%20%23%

12%13%

Q4 14Q3 14Q2 14Q1 14Q4 13Q3 13Q2 13Q1 13Q4 12Q3 12Q2 12Q1 12

12%9%

5%5%

0%2%

10%

3%2%1%

EMs outside China

0%1%

-2%-3%

4% 8%1%Q4 14Q3 14Q2 14Q1 14Q4 13Q3 13Q2 13Q1 13Q4 12Q3 12Q2 12Q1 12

+4% +8%-1%

92

Then and Now - Medical Science Liaisons (MSLs)

410MSLs inInternational140 Internationalby year-end

MSLs inI t ti l

140International

THENNOW

THEN

93

Then and Now - opinion leaders

9181O i i l d

1000+ Opinion leadersf I t ti l

9181Opinion leadersBrilinta, Diabetes & Respiratory

for International

NOWTHEN

94

THEN

Then and Now

International has ongoing Externally Sponsored

Research Programmes213

Set a strategic prioritySet a strategic priorityto achieve scientific leadership International and Japan

kick off I-DISCOVER studykick off I-DISCOVER study

NOWTHEN

95

THEN

China:AstraZeneca #2 multi-national company

• Largest MNC sales force5,720 Largest MNC sales force

• Hospital coverage up ~40%

• 73 clinical development projects2 809

3,0913,338

4,172

+18%

+22%

• Taizhou manufacturing site opened; 4.5bn tablets in 2018

1.1 1.3 1.5 1.82.2

2,809

+16%+16%

2010 2011 2012 2013 2014Sales ($bn) Field force

Sales growth at CER

96

Russia:Returned to double digit growth rate

• Fastest growing MNC i t il t

15%

14%

17%

Sales growth at CER (MAT)

in retail segment

• Patient affordability programmes across 27 regions 40 000 people

13%14%

9% regions, 40,000 people enrolled

• 550 clinical trial sites in 37 cities4%

9%8%

in 37 cities

• Manufacturing plant opening late 2015

SS

1%

Dec-14Jun-14 Sep-14Jun-13 Mar-14Sep-13 Dec-13Mar-13

97

Brazil:Strong launch capabilities in Emerging Markets

Market share uptake vs. competitor

3,0 2 8,

2,5

2,0

2.8

.sha

re

,

1,5

1,01.0

AP

DO

T m

kt

,

0,5

O

M36M24M12M01

Brilinta Competitor98

Source: IMS

Japan: Success in primary care drives increasing market share

2012 2013 2014 Sep YTD

Japan market company rankingsKey brand value market share (%)

44%

1 Pfizer Pfizer Pfizer

2 Takeda Takeda Takeda

3 D.S D.S D.S

4 MSD MSD Chugai

#10 brandby growth

33%

42%

4 MSD MSD Chugai

5 Chugai Chugai MSD

6 Novartis Novartis Novartis

7 M.T. M.T. M.T.AZ

#3 brand by sales

#1 brand in Japan 8 Eisai Sanofi

9 Sanofi Sanofi

10 GSK Eisai GSK

11 Astellas GSK Otsuka

AZ

AZ#1 brand in Japan#3 brandby growth

#8 brand by sales

12 Otsuka EisaiAZ2010 2011 2012 2013 2014

Source: IMS

99

Japan:Established in oncology; rapidly growing primary care

Top brands by sales

FY 2014 Growth CER PartnerFY 2014 Growth CER Partner

-12%792 Oncology

+1%537 Crestor

+38%

+27%222

378

Symbicort

Nexium

100

y

Japan:Preparing for first new oncology product; AZD9291

EGFR mutation rate (exon 19-21)NSCLC patients

First line prescription shareEGFR mutation positive NSCLC

~32%

15%

57%

pemetrexed

Iressa

~15%12%

15%

erlotinib

pemetrexed

7%

6%

afatinib

bevacizumab

101

East Asians Non-Asians

Source: Mitsudomi T, Cancer Sci 98:1817-1824, 2007; AZ Japan web diary survey Q3 NSCLC

Finance

2014 Top Product SalesTherapy area Total sales

($m)Total growth

rate*US sales

($m)US

growth rate*EU sales

($m)EU

growth rate*Est. ROW

($m)Est ROW

growth rate*EM

($m)EM

growth rate*($m) rate ($m) growth rate ($m) growth rate ($m) growth rate ($m) growth rate

RIA 5,063 10% 1,748 15% 1,747 -4% 582 11% 986 27%

Symbicort 3,801 10% 1,511 23% 1,462 -4% 458 17% 370 22%

Pulmicort 946 11% 211 -6% 162 -6% 97 -6% 476 35%

CVMD 9,802 12% 4,451 17% 2,283 8% 951 -3% 2,117 17%

Crestor 5,512 -1% 2,918 0% 1,200 -3% 667 -10% 727 11%

Onglyza 820 119% 481 82% 155 175% 59 210% 125 251%

Brilinta 476 70% 146 100% 231 40% 33 106% 66 133%

Bydureon 440 191% 374 185% 57 235% 5 400% 4 100%

Byetta 327 59% 199 31% 81 119% 27 164% 20 200%

Oncology 3,027 -2% 411 7% 788 -6% 883 -11% 945 8%

Faslodex 720 7% 340 5% 245 10% 59 3% 76 14%

Iressa 623 -1% - - 166 -7% 177 -4% 280 6%

ING 8,203 -7% 3,510 -12% 1,820 -7% 1,094 -7% 1,779 3%

Nexium 3,655 -4% 1,876 -12% 368 2% 606 9% 805 5%

Seroquel XR 1,224 -8% 738 -1% 343 -18% 44 -35% 99 -

103

Synagis 900 -15% 499 -19% 401 -9% - - - -

* All growth rates at constant exchange rates.

Profit & loss: Redeployment

C SG&A

$mTotal IT costs Total facilities costs

11%

Core SG&A

32%24% Examples

$m-11%-8%

68%76%

G&ASM&M

2012 2014 2012 2014

68%

2012 2014

Has supported increased investment in:• Growth platforms, including Emerging Markets build-up• Unprecedented # of on-going/upcoming launches

2012 2014 2012 20142012 2014

Structural change in SG&A due to redeployment of resourcesFrom fixed to more variable costs Unprecedented # of on going/upcoming launchesFrom fixed to more variable costs

104SM&M: Sales, Marketing & Medical

Balance sheet: Flexibility

87

Cash conversion cycle (days)Debt & cash• Continue to target a strong, investment-grade

Peer average

69

credit rating• Moody’s: A2 Stable outlook• Standard & Poor’s: AA- Negative outlook

• November 2014: 0 875% EUR 2021 medium45

2012 2014

• November 2014: 0.875% EUR 2021 medium-term notes (€750m); oversubscribed 4 times

• Cash and cash equivalents end-2014 $6.4bn

• Net debt $3.2bn

Strategic flexibility to support progressive dividend return to growth and accelerating pipeline

2012 2014$

Strategic flexibility to support progressive dividend, return to growth and accelerating pipeline

105Cash conversion calculated as DSO + DIO - DPO at the end of the year (in days) as a function of net sales

2013-2017: Growth platforms expected to continue delivering

$ Revenue $ RevenueGrowth Late-stage$2013

$ Revenue2017

E t bli h d d t

platformsg

pipeline

Established products, Crestor, Nexium,

Seroquel LoE in US and EU

Illustrative2013 revenue is net sales as reported. Targets are at constant exchange rates, reflecting net sales.

106

2017-2023: Accelerating pipeline expected to take over

Growth

Late-stagepipeline

2023Revenue

Target: >$45bn

$ Revenue $ Revenue

Established products

Growth platforms

$ Revenue2013

$ Revenue2017

Illustrative2013 revenue is net sales as reported. Targets are at constant exchange rates, reflecting net sales.

107

$53bn returned to shareholders over 10 years

2005 – 2014 cash distributions ($bn):$30.0bn in dividends

6.0

$$23.2.bn in share buybacks

1 72.2

2.6 2.7 3.0 3.4 3.7 3.7 3.5 3.5

3.0

4.1 4.2

2.6 2.6

1.7

0.6 - - -

2005 2006 2007 2008 2009 2010 2011 2012 2013 2014

Source: annual reports108

2005 2006 2007 2008 2009 2010 2011 2012 2013 2014Dividends Buybacks

Disciplined value-creating framework

• R&D • Business

Established Growth f

Development

Cash Pipelineproducts platforms

• 2015-2016:

• Progressive dividend policy

flowPipeline

• Brilinta

• Diabetes

• Respiratory

Emerging Markets

– 8-10 NME / LE approvals

– 14-16 NME / LE submissions

policy• Efficient

capital structure

• Emerging Markets

• Japan

• Oncology

• Phase III: 13 NMEs• Phase II: 28 NMEs• Phase I: 38 NMEs109

Incentives aligned with shareholder value creation

✔(30%)

✔(25%)

–

STIPSP*** AZIP***

LTI plans

Achieve scientific leadership Delivery of pipeline

(30%) (25%)

✔(30%)

✔(25%)

–

leadership

Return to growth Delivery ofsales growth Shareholder

value

✔(40%)

✔*

(25%)–

✔

Achieve group financial targets

T t l h h ld

Delivery offinancial targets

D li f di id d

value creation

– ✔(TSR – 25%)

✔**

(Div – 100%)Total shareholder return & dividend

Delivery of dividends & other shareholder returns

Aligned with strategic priorities & consistent with long-term plan

Notes:* Cumulative free cash flow target ** DPS = Dividend per share, maintained minimum dividend cover*** PSP = Performance Share Plan; AZIP = Investment Plan

110

Debt and credit ratings

Debt Maturity Profile Debt maturity profile

2,000

2,500

3,000

Debt Maturity Profile

GBP

Debt maturity profile

0

500

1,000

1,500$m

GBP

EUR

USD

• November 2014: 0.875% EUR 2021 medium-term notes (€750m); oversubscribed 4 times• The Board intends to maintain a strong, investment grade credit rating. The Company is currently rated as:

• Moody’s: A2 Stable outlook

2015 2016 2017 2018 2019 2020 2021 2022 2023 2031 2037 2042

• Moody s: A2 Stable outlook• Standard & Poor’s: AA- Negative outlook

• AstraZeneca believes that it is important to preserve balance sheet strength, particularly during periods of revenue transition.

• Alongside gross debt, we choose to hold a significant cash balance to meet operational funding needs and periodicAlongside gross debt, we choose to hold a significant cash balance to meet operational funding needs and periodic settlements of liabilities. The cash and cash equivalents balance as at 31 December 2014 was $6.4bn.

1111 FX converted at December 2014 spot rates (USD/EUR 0.822538 & USD/GBP 0.642715)

Appendix

Investor Relations Contacts

Contact Email Phone numberContact Email Phone number

UK

Thomas Kudsk Larsen [email protected] T: +44 207 604 8199M: +44 781 852 4185M: +44 781 852 4185

Eugenia Litz [email protected] T: +44 207 604 8233M: +44 788 473 5627

Craig Marks [email protected] T: +44 207 604 8591Craig Marks [email protected] T: 44 207 604 8591M: +44 788 161 5764

Christer Gruvris [email protected] T: +44 207 604 8126M: +44 782 783 6825

Mary Pericleous [email protected] T: +44 207 604 8127M: +44 758 540 4874

US

Karl Hård karl j hard@astra eneca com T +44 207 604 8123Karl Hård [email protected] T: +44 207 604 8123M: +44 778 965 4364

113

Confidentiality Notice This file is private and may contain confidential and proprietary information. If you have received this file in error, please notify us and remove it from your system and note that you must not copy, distribute or take any action in reliance on it. Any unauthorized use or disclosure of the contents of this file is not permitted and may be unlawful. AstraZeneca PLC, 2 Kingdom Street, London, W2 6BD, UK, T: +44(0)20 7604 8000, F: +44 (0)20 7604 8151, www.astrazeneca.com(0) 0 60 8 5 , ast a e eca co

114

Documents

Investor Relations General Presentation