Slide 1: Investor science event: ESMO 2017
Investor science event: ESMO 2017 Presentation and webcast for investors and analysts, Madrid, Spain 10 September 2017
Slide 2: Forward-looking statements
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, pe
Slide 3: Presenters
Presenters Pascal Soriot Sean Bohen Executive Director and Executive Vice President, Chief Executive Officer Global Medicines Development and Chief Medical Officer Jean-Charles Soria David Planchard (MD, PhD) Investigator, Tagrisso’s Investigator, Imfinzi’s PACIFIC trial, FLAURA trial, Professor Dep
Slide 4: Agenda
Agenda Welcome Pipeline Tagrisso’s FLAURA trial Imfinzi’s PACIFIC trial Business, news flow and Q&A Antibody that blocks inhibitory signals from the tumour to cells of the immune system, resulting in enhanced anti- tumour immunity 4
Slide 5: Late-stage pipeline overview
Late-stage pipeline overview Significant opportunities from lifecycle and potential new medicines Cardiovascular & Oncology Respiratory Metabolic Diseases Lynparza1, 2 ZS-92 benralizumab1, 2 multiple cancers hyperkalaemia severe, uncontrolled asthma / COPD Tagrisso1, 2 roxadustat2 tralokinumab lung
Slide 6: AstraZeneca Oncology: Strategic priorities support the return to growth
AstraZeneca Oncology Strategic priorities support the return to growth Multiple cancers Lung cancers Blood cancers acalabrutinib • Ovarian and breast • 2L T790Mm1 • Locally-advanced (Stage • AstraZeneca’s first, cancers • 1L EGFRm2 III), unresectable NSCLC potential new medicine in • Lifecycle progr
Slide 7: Agenda
Agenda Welcome Pipeline Tagrisso’s FLAURA trial Imfinzi’s PACIFIC trial Business, news flow and Q&A Antibody that blocks inhibitory signals from the tumour to cells of the immune system, resulting in enhanced anti- tumour immunity 7
Slide 8: AstraZeneca at ESMO 2017
AstraZeneca at ESMO 2017 Broad and deep presence, outside FLAURA and PACIFIC >40 Example from early-stage pipeline Company-sponsored and supported presentations AZD9150 (STAT3 ASO) + Imfinzi 2 Encouraging anti-tumour activity and deep responses observed in R/M-HNSCC PD-(L)1-naïve patients: • 25% ORR
Slide 9: News: Lynparza
News: Lynparza Broad US label in ovarian cancer; leading development plan 2x2 tablets Broad development programme Combination with IO (Keytruda, Imfinzi) 2L all-comers ovarian Combination with DDR2 Combination with VEGF(r)3 4L+ BRCAm1 ovarian Monotherapy BRCAm Biomarker HRRm4 Data in advanced negati
Slide 10: News: Acalabrutinib
News: Acalabrutinib AstraZeneca’s first, potential new medicine in blood cancers 21 Ongoing trial • Breakthrough Therapy Designation in MCL • US regulatory submission ✓ clinical trials >2,000 Phase IB/II Phase II Phase III Phase II Phase III acceptance in MCL – Regulatory decision WM1 MCL CLL2 lates
Slide 11: AstraZeneca in non-small cell lung cancer (NSCLC)
AstraZeneca in non-small cell lung cancer (NSCLC) Overview of medicines, successful & ongoing Phase III trials PEARL Patients with no (2020) EGFR-mutated or POSEIDON CTx ALK-translocated (2019) tumours ~75-80% of patients NEPTUNE (H2 2018) = Imfinzi + treme = Imfinzi ADJUVANT (2020) PACIFIC1 (2019 f
Slide 12: NSCLC: Ongoing Phase III trials
NSCLC: Ongoing Phase III trials Focus today Present in targeted and IO medicines ADAURA ADJUVANT PACIFIC FLAURA MYSTIC NEPTUNE POSEIDON PEARL ARCTIC Stage I-III Stage Ib-IIIa Stage III Stage IV / 1L Stage IV / 1L Stage IV / 1L Stage IV / 1L Stage IV / 1L Stage IV / 3L EGFRm unresectable EGFRm EGFR/A
Slide 13: Agenda
Agenda Welcome Pipeline Tagrisso’s FLAURA trial Imfinzi’s PACIFIC trial Business, news flow and Q&A Antibody that blocks inhibitory signals from the tumour to cells of the immune system, resulting in enhanced anti- tumour immunity 13
Slide 14: FLAURA trial: double-blind study design
FLAURA trial FLAURA DOUBLE-BLIND STUDY DESIGN Patients with locally advanced or metastatic NSCLC Osimertinib (80 mg p.o. qd) Key inclusion criteria Stratification by (n=279) • ≥18 years* mutation status RECIST 1.1 assessment every • WHO performance status 0 / 1 (Exon 19 deletion Randomised 1:1 6 wee
Slide 15: FLAURA trial: baseline characteristics
FLAURA trial BASELINE CHARACTERISTICS Osimertinib SoC* Characteristic, % (n=279) (n=277) Sex: male / female 36 / 64 38 / 62 Age, median (range), years 64 (26–85) 64 (35–93) Race: White / Asian / other# 36 / 62 / 1 36 / 62 / 1 Smoking status: never / ever 65 / 35 63 / 37 CNS metastases at study entry
Slide 16: FLAURA trial: primary endpoint PFS
FLAURA trial PRIMARY ENDPOINT: PFS BY INVESTIGATOR ASSESSMENT 342 events in 556 patients at DCO: 62% maturity; osimertinib: 136 events (49%), SoC: 206 events (74%) 1.0 Median PFS, months (95% CI) Osimertinib 18.9 (15.2, 21.4) Probability of progression-free survival 0.8 SoC 10.2 (9.6, 11.1) 0.6 HR 0
Slide 17: FLAURA trial: PFS across subgroups
FLAURA trial PFS* ACROSS SUBGROUPS Favours osimertinib Favours SoC Hazard ratio (95% confidence interval) Subgroup Overall (n=556) Log Rank (primary) 0.46 (0.37, 0.57) Cox PH 0.46 (0.37, 0.57) Sex Male (n=206) 0.58 (0.41, 0.82) Female (n=350) 0.40 (0.30, 0.52) Age at screening <65 (n=298) 0.44 (0.33
Slide 18: FLAURA trial: PFS with and without CNS metastases
FLAURA trial PFS* IN PATIENTS WITH AND WITHOUT CNS METASTASES AT STUDY ENTRY With CNS metastases (n=116) Without CNS metastases (n=440) Median PFS, months (95% CI) Median PFS, months (95% CI) 1.0 Osimertinib 15.2 (12.1, 24.4) 1.0 Osimertinib 19.1 (15.2, 23.5) SoC 9.6 (7.0, 12.4) SoC 10.9 (9.6, 12.3)
Slide 19: FLAURA trial: overall survival interim analysis
FLAURA trial OVERALL SURVIVAL INTERIM ANALYSIS 141 deaths in 556 patients at DCO: 25% maturity; osimertinib: 58 deaths (21%), SoC: 83 deaths (30%) 1.0 0.8 Probability of overall survival 0.6 0.4 Median overall survival HR 0.63 ǂA p-value of <0.0015 was required for 0.2 Osimertinib Not reached (95% C
Slide 20: FLAURA trial: safety summary
FLAURA trial FLAURA SAFETY SUMMARY AE, any cause*, n (%) Osimertinib (n=279) SoC (n=277) Any AE 273 (98) 271 (98) Any AE Grade ≥3 94 (34) 124 (45) Any AE leading to death 6 (2) 10 (4) Any serious AE 60 (22) 70 (25) Any AE leading to discontinuation 37 (13) 49 (18) AE, possibly causally related#, n (
Slide 21: FLAURA trial: conclusions
FLAURA trial CONCLUSIONS • Osimertinib resulted in a significant improvement in PFS over SoC, HR 0.46 (95% CI 0.37, 0.57); p<0.0001 • 54% reduction in risk of progression or death relative to SoC, with early separation of KM curves • Consistent benefit in patients with and without CNS metastases at
Slide 22: Agenda
Agenda Welcome Pipeline Tagrisso’s FLAURA trial Imfinzi’s PACIFIC trial Business, news flow and Q&A Antibody that blocks inhibitory signals from the tumour to cells of the immune system, resulting in enhanced anti- tumour immunity 22
Slide 23: PACIFIC trial: study design
PACIFIC trial PACIFIC: Study Design Phase III, Randomized, Double-blind, Placebo-controlled, Multicenter, International Study • Patients with stage III, locally Durvalumab Co-primary endpoints advanced, unresectable NSCLC 10 mg/kg q2w for who have not progressed following • PFS by BICR using RECIST
Slide 24: PACIFIC trial: baseline characteristics (ITT)
PACIFIC trial Baseline Characteristics (ITT) Durvalumab Placebo (N=476) (N=237) Age Median (range), years 64 (31–84) 64 (23–90) ≥65 years, % 45.2 45.1 Male, % 70.2 70.0 WHO performance status score, %* 0/1 49.2 / 50.4 48.1 / 51.5 Smoking status, % Current / Former / Never 16.6 / 74.4 / 9.0 16.0 / 75
Slide 25: PACIFIC trial: patient disposition
PACIFIC trial Patient Disposition Durvalumab Placebo (N=476) (N=237) Received treatment, n (%) 473 (99.4) 236 (99.6) Completed 12 months of treatment, n (%) 202 (42.7) 71 (30.1) Discontinued study treatment, n (%) 241 (51.0) 153 (64.8) Patient decision 14 (3.0) 12 (5.1) Adverse event 73 (15.4) 23 (9
Slide 26: PACIFIC trial: PFS by BICR
PACIFIC trial PFS by BICR (Primary Endpoint; ITT) Stratified hazard ratio, 0.52 (95% CI, 0.42–0.65) Two-sided P<0.0001 1.0 0.9 Durvalumab Placebo (N=476) (N=237) 0.8 Median PFS (95% CI), months 16.8 (13.0–18.1) 5.6 (4.6–7.8) 0.7 12-month PFS rate (95% CI) 55.9% (51.0–60.4) 35.3% (29.0–41.7) PFS prob
Slide 27: PACIFIC trial: PFS subgroup analysis by BICR
PACIFIC trial PFS Subgroup Analysis by BICR (ITT) Durvalumab Placebo Unstratified HR* No. of patients (95% CI) All patients 476 237 0.55 (0.45–0.68) Male 334 166 0.56 (0.44–0.71) Sex Female 142 71 0.54 (0.37–0.79) <65 years 261 130 0.43 (0.32–0.57) Age at randomization ≥65 years 215 107 0.74 (0.54–1
Slide 28: PACIFIC trial: incidence of new lesions
PACIFIC trial Incidence of New Lesions by BICR (ITT) Durvalumab Placebo New lesion site* (N=476) (N=237) Any new lesion, n (%) 97 (20.4) 76 (32.1) Lymph nodes 27 (5.7) 27 (11.4) Brain 26 (5.5) 26 (11.0) Lung 56 (11.8) 41 (17.3) Liver 9 (1.9) 8 (3.4) Adrenal 3 (0.6) 5 (2.1) Bone 8 (1.7) 6 (2.5) Other
Slide 29: PACIFIC trial: time to distant metastasis or death
PACIFIC trial Time to Distant Metastasis or Death by BICR (ITT) Stratified hazard ratio, 0.52 (95% CI, 0.39–0.69) Two-sided P<0.0001 1.0 Durvalumab Placebo Probability of death or distant metastasis 0.9 Median time (95% CI), 23.2 (23.2–NR) 14.6 (10.6–18.6) 0.8 months 0.7 0.6 0.5 Durvalumab 0.4 0.3 0
Slide 30: PACIFIC trial: safety summary
PACIFIC trial Safety Summary* Durvalumab Placebo (N=475) (N=234) Any-grade all-causality AEs, n (%) 460 (96.8) 222 (94.9) Grade 3/4 142 (29.9) 61 (26.1) Grade 5 21 (4.4) 13 (5.6) Leading to discontinuation 73 (15.4) 23 (9.8) Any-grade treatment-related AEs, n (%) 322 (67.8) 125 (53.4) SAEs, n (%) 13
Slide 31: PACIFIC trial: summary
PACIFIC trial Summary • Durvalumab demonstrated a statistically significant and robust improvement in PFS versus placebo (HR 0.52; P<0.0001; median improvement of >11 months) at a planned interim analysis • PFS improvement with durvalumab was observed across all pre-specified subgroups • Durvalumab
Slide 32: Agenda
Agenda Welcome Pipeline Tagrisso’s FLAURA trial Imfinzi’s PACIFIC trial Business, news flow and Q&A Antibody that blocks inhibitory signals from the tumour to cells of the immune system, resulting in enhanced anti- tumour immunity 32
Slide 33: Tagrisso: EGFR-mutated 1L NSCLC
Tagrisso: EGFR-mutated 1L NSCLC Global prevalence of the EGFR mutation EGFRm prevalence 1L NSCLC ~70K addressable patients in top-8 countries1 1. Top-8 countries include China, France, Germany, Italy, Japan, Spain, UK, USA. Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4633915/, Figure 2, Ast
Slide 34: Tagrisso: Potential to become 1L SoC
Tagrisso: Potential to become 1L SoC Significant patient benefits, including in CNS PFS T790Mm neg. ~25k pts EGFRm ~70k pts HR=0.46 / 18.9m Lower risk of progression or death OS trend HR=0.63 “ At the first-line diagnosis, potential T790M progression is not known: T790Mm Clinically-meaningful OS at
Slide 35: Imfinzi: Locally-advanced (Stage III), unresectable NSCLC
Imfinzi: Locally-advanced (Stage III), unresectable NSCLC New, refreshed epidemiology data shows more unresected patients ~105,000 72% ~2-3 years ~76,000 ahead of the closest competitor Potential to expand 47% ~36,000 >$1bn sales opportunity that supports return to growth Total Stage III Unresected
Slide 36: Oncology: Busy forthcoming news flow
Oncology: Busy forthcoming news flow Phase III data readouts and regulatory actions selumetinib Imfinzi +/- treme thyroid cancer bladder cancer 1L DANUBE regulatory submission regulatory submission Regulatory Imfinzi +/- treme moxetumomab Imfinzi +/- treme lung cancer 3L ARCTIC leukaemia H&N cancer
Slide 37: Oncology: Our strategic priorities
Oncology: Our strategic priorities acalabrutinib 37
Slide 38: Q&A
Q&A
Slide 39: Use of AstraZeneca webcast, conference call and presentation slides
Use of AstraZeneca webcast, conference call and presentation slides The AstraZeneca webcast, conference call and presentation slides (together the ‘AstraZeneca Materials’) are for your personal, non- commercial use only. You may not copy, reproduce, republish, post, broadcast, transmit, make availab
Slide 40: Investor science event: ESMO 2017
Investor science event: ESMO 2017 Presentation and webcast for investors and analysts, Madrid, Spain 10 September 2017