Astrazeneca Plc · LSE:AZN
Astrazeneca — American College of Cardiology 2015
39 slides from Astrazeneca's conference presentation, Mar 16, 2015
Slide 1: Investor science conference call: American College of Cardiology 2015
Investor science conference call: American College of Cardiology 2015 San Diego, California, USA 16 March 2015
Slide 2: Cautionary statement regarding forward-looking statements
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
Slide 3: Introduction
Introduction Thomas Kudsk Larsen, Head of Investor Relations
Slide 4: Welcome, agenda & introduction
Welcome, agenda & introduction Welcome PEGASUS-TIMI 54 trial BRILINTA® / BRILIQUE™ clinical & business status Q&A Estimated duration up to one hour 4
Slide 5: PEGASUS-TIMI 54 trial
PEGASUS-TIMI 54 trial Dr. Marc Sabatine, PEGASUS TIMI-54 Primary Investigator Brigham and Women’s Hospital, Massachusetts, USA
Slide 6: PEGASUS-TIMI 54
WA PEGASUS TIMI 54 Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin Marc S. Sabatine, MD, MPH on behalf of the PEGASUS-TIMI 54 Executive & Steering Committees and Investigators NCT00526474
Slide 7: Background
RE Background ¢ PEGASUS TiMI54 * Current guidelines recommend adding a P2Y,, receptor antagonist to aspirin only for the first year after an acute coronary syndrome (ACS) * However, several lines of evidence suggest more prolonged therapy may be beneficial in Pts w/ prior MI — Landmark analyses from
Slide 8: Hypothesis
IE Hypothesis TIMI54 The addition of ticagrelor to standard therapy (including low-dose aspirin) would reduce the incidence of major adverse cardiovascular events during long-term follow-up in patients with a history of Ml ‘An Academic Research Organization of Brigham and Women’s Hospital and Harvar
Slide 9: Trial Organization
PEGASUS IE Trial Organization ¢ TIMI 54 TIMI Study Group Eugene Braunwald (Chair) Marc P. Bonaca (Co-PI) S Morin & P Fish (Operations) Executive Cmte Eugene Braunwald (Chair) Deepak L. Bhatt Ph. Gabriel Steg Sponsor: AstraZeneca Peter Held Per Johanson Barbro Boberg Independent Data Monitoring Cmte
Slide 10: Steering Committee
10 IE PEGASUS Steering Committee TIMI 54 Argentina R. Diaz/E Paolasso Australia P Aylward Belgium F Van der Werf Brazil J Nicolau Bulgaria A Goudev Canada P Theroux Chile R Corbalan China DHu Colombia DIsaza Czech Republic J Spinar France G Montalescot/PG Steg 15] Ci] ‘An Academic Research Organizat
Slide 11: Trial Design
11 IE Trial Design ¢ PEGASUS TIMI 54 Stable pts with history of MI 1-3 yrs prior +21 additional atherothrombosis risk factor RANDOMIZED DOUBLE BLIND Planned treatment with ASA 75 — 150 mg/d & Standard background care Ticagrelor Ticagrelor 90 mg bid 60 mg bid iti Follow-up Visits Minimum 1 year follo
Slide 12: Key Inclusion & Exclusion Criteria
N= Key Inclusion & Exclusion Criteria ¢ PEGASUS TIMI54 KEY INCLUSION * Age 250 years * Atleast 1 of the following: — Age 265 years — Diabetes requiring medication — 2"4 prior MI (>1 year ago) - Multivessel CAD — CrCl <60 mL/min * Tolerating ASA and able to be dosed at 75-150 mg/d 12 ‘An Academic Res
Slide 13: Endpoints
AS Endpoints é PEGASUS TiMI54 ¢ Efficacy: hierarchical testing — Primary: cardiovascular (CV) death, MI, or stroke — Secondary: CV death; all-cause mortality — Prespecified exploratory: substituting coronary for CV death; other individual coronary and cerebrovascular ischemic outcomes; pooling ticag
Slide 14: Global Enrollment
RLS Global Enrollment ¢ PEGASUS TIMi54 21,162 patients randomized at 1161 sites in 31 countries between 10/2010 — 5/2013 Czech Rep: 870 China: 383 { Philippines: 250 4! Peru: 245 f in ° Chile: 322 Australia: 327 Argentina: 499 South Africa: 473 14 13] g ‘An Academic Research Organizati Brigham and W
Slide 15: Follow-Up
= Follow-Up ¢ PEGASUS TIMI 54 Randomized 21,162 patients Placebo (N=7067) Follow-up median 33 months (IQR 28-37) Minimum 16 months, maximum 47 months Premature perm. drug discontinuation 12%lyr 11%lyr BY%lyr Withdrew consent 0.7% total 0.7% total 0.7% total Lost to follow-up 3 patients 6 patients 1
Slide 16: Baseline Characteristics
4 l= Baseline Characteristics ¢ PEGASUS TIMI 54 Characteristic Value Age - yr, mean (SD) 65 (8) Female 24 Hypertension 78 Hypercholesterolemia 77 Current smoker 17 Diabetes mellitus 32 Estimated GFR <60 mL/min/1.73m? 23 History of PCI 83 Multivessel coronary disease 59 History of more than 1 prior M
Slide 17: Baseline Characteristics
4 l= Baseline Characteristics ¢ PEGASUS TIMI 54 Qualifying Event Years from MI — median (IQR) 1.7 (1.2 — 2.3) History of STEMI 53 History of NSTEMI 41 MI type unknown 6 50 40 % of patients nN o zz — <3 3-4 4-5 5-6 >6 Years from qualifying MI to end of follow-up 17 8 ] ‘An Academic Research Organizat
Slide 18: Baseline Characteristics
ZS Baseline Characteristics ¢ PEGASUS Characteristic Value TIMI 54 Qualifying Event Years from MI — median (IQR) 1.7 (1.2 — 2.3) History of STEMI 53 History of NSTEMI 41 MI type unknown 6 Medications at enrollment Aspirin (any dose) 99.9 Dose 75-100 mg/d 97.3 Statin 93 Beta-blocker 82 ACEI or ARB 80
Slide 19: Primary Endpoint
19 = Primary Endpoint ¢ PEGASUS TIMI 54 10 N = 21,162 9 Median follow-up 33 months Placebo (9.0%) 8 Ticagrelor 90 (7.8%) Ticagrelor 60 (7.8%) 7 6 CV Death, MI, or Stroke (%) 89 Ticagrelor 90 mg HR 0.85 (95% Cl 0.75 — 0.96) P=0.008 Ticagrelor 60 mg HR 0.84 (95% Cl 0.74 — 0.95) P=0.004 0 3 6 9 12 15 1
Slide 20: Components of Primary Endpoint
N= Components of Primary Endpoint ¢ PEGASUS TIMI 54 Endpoint HR (95% Cl. P value —_i— 0.85 (0.75-0.96) 0.008 CV Death, MI, or Stroke —eo— 0.84 (0.74-0.95) 0.004 (1558 events) ——_= 0.84 (0.76-0.94) 0.001 —_i_ 0.87 (0.71-1.06) 0.15 CV Death —_e—_; 0.83 (0.68-1.01) 0.07 (566 events) | 0.85 (0.71-1.00)
Slide 21: Other Efficacy Outcomes
N= Other Efficacy Outcomes ¢ PEGASUS TIMI 54 Ticagrelor Ticagrelor Placebo Ticagrelor90 Ticagrelor 60 90mg bid 60mgbid (N=7067) vs Placebo vs Placebo Outcome (N=7050) (N=7045) p-value p-value 3-yr KM rate (%) Coronary Death, HR 0.82 HR 0.83 MI, or Stroke _ i _ P=0.002 P=0.003 Coronary Death HR 0.81
Slide 22: Efficacy for 1° EP in Subgroups
XS Efficacy for 1° EP in Subgroups ¢ PEGASUS TIMI 54 Hazard Ratio (95% Cl) Hazard Ratio (95% Cl) Subgroup Pts Ticagrelor 90 mg vs Placebo Ticagrelor 60 mg vs Placebo All Patients 21,162 & Age at Randomization H Age <75 18,079 a Age 275 3,083 a Female 5,060 = Male 16,102 Si Qualifying MI i NSTEMI 8,5
Slide 23: Bleeding
23 IE PEGASUS 89 Bleeding TIMI 54 5, Ticag 90: HR 2.69 (1.96-3.70) Ticag 60: HR 2.32 (1.68-3.21) = Ticagrelor 90 mg = Ticagrelor 60 mg ‘An Academic Research Organization of Brigham and Women’s Hospital and Harvard Medical School S4 = P<0.001 = Placebo G e326 : 2.3 & 5 P<0.001 = P=NS P=NS P=NS 1342 :
Slide 24: Other Adverse Events
WA Other Adverse Events ¢ PEGASUS TIMI 54 Ticagrelor Ticagrelor Placebo Ticagrelor90 Ticagrelor 60 90mg bid 60mghbid (N=6996) vs Placebo vs Placebo Adverse Event = (N=6988) (N=6958) p-value p-value 3-yr KM rate (%) Dyspnea AE 18.9 15.8 6.4 P<0.001 P<0.001 Leading to study drug dic 6.5 4.6 0.8 P<0.00
Slide 25: Summary
IE Summary TIMI 54. « Adding ticagrelor to low-dose aspirin in stable patients with a history of MI reduced the risk of CV death, MI or stroke * The benefit of ticagrelor was consistent — For both fatal & non-fatal components of primary endpoint — Over the duration of treatment — Among major clinica
Slide 26: Conclusion
IE Conclusion TIMI54 Long-term dual antiplatelet therapy with low-dose aspirin and ticagrelor should be considered in appropriate patients with a myocardial infarction. 26 ‘an Aeademi Research Organization of ID sirens tomers Hosp ard Harvard Media! Shel
Slide 27: BRILINTA® / BRILIQUE™ Clinical & business status
BRILINTA® / BRILIQUE™ Clinical & business status Tom Keith-Roach, BRILINTA® Task Force leader
Slide 28: CVD deaths worldwide
Global #1 cause of death1,2, >17m per year1 Cardiovascular disease (CVD) worldwide 17.3 million to 23.3 million 35% growth ~70% CVD deaths worldwide, of total global CVD deaths millions are due to ischaemic heart disease and cerebrovascular disease3 2008 2030 Year Low-to-Middle Income High Income So
Slide 29: BRILINTA® / BRILIQUE™ Indicated for the treatment of ACS
BRILINTA® / BRILIQUE™ Indicated for the treatment of ACS Indication PLATO1 study, epidemiology • Indicated to reduce the rate of thrombotic CVD events in ACS incidence patients with ACS 4.0 million • Shown to reduce the rate of a combined end point of CVD STEMI NSTEMI Unstable angina death, MI, or s
Slide 30: US performance: momentum has led to branded NBRx leadership
US performance Momentum has led to branded NBRx leadership Branded oral anti-platelet (OAP) retail new-to-brand Monthly brand total prescriptions (TRx) and NBRx prescription (NBRx) share1 share, OAP class2 BRILINTA® Competitor TRx share NBRx share 2,800 2,600 8.2% 2,475 2,400 Retail NBRx Volume 2,20
Slide 31: Global performance: positive momentum continues through FY 2014
Global performance Positive momentum continues through FY 2014 OAP share, volume: Retail + hospital1 Monthly brand share, OAP class3 8% US 7% 6% Australia UK 5% France Market share Germany Spain 12% 4% Italy Italy 3% Spain 2% Germany -5% UK US France 4% 0% 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30
Slide 32: Significant future opportunities
Significant future opportunities International guidelines support BRILINTA® / BRILIQUE™ for >65% patients treated for 12 months ACS discharge share1 Patients reaching 12 months2 80% Guidelines support Country % patients at 12 months % ACS drug treated patients 60% >65% share Italy 67% Australia 51%
Slide 33: Beyond 12 months: patients remain at significant risk
Beyond 12 months Patients remain at a significant risk APOLLO; late-breaking registry presentation at the 2014 European Society of Cardiology in Patients who are event free in first year after their index event will suffer a MI, stroke or death in the subsequent three years 33
Slide 34: PEGASUS-TIMI 54 study meets primary endpoint in both 60mg and 90mg doses
PEGASUS-TIMI 54 study of BRILINTA® / BRILIQUE™ meets primary endpoint in both 60mg and 90mg doses PEGASUS-TIMI 54 study PEGASUS-TIMI 54 study, epidemiology2 • Investigated 60mg and 90mg ticagrelor vs. placebo in Prior MI 13-36 months patients (low-dose aspirin) aged 50 and older with a 4.5 million h
Slide 35: Outstanding collaboration with TIMI Study Group
Outstanding collaboration with TIMI Study Group Publication, regulatory, prepare to launch Study metrics Publication, regulatory Towards launch • 21,000 patients in 31 • FDA and EMA • Regulatory submission countries submissions complete • Pre-launch planning • >210,000 patient visits • Parallel pres
Slide 36: PARTHENON programme: four regulatory submissions expected in three years
PARTHENON programme Four regulatory submissions expected in three years 2015 2016 2017 2018 Patients OAP Billion Days of Comparator enrolled access Therapy PLATO Acute Coronary Syndrome 18,624 clopidogrel 20% 1.3% Launched PEGASUS Prior MI 21,162 placebo 20% 1.4% Data Expected launch SOCRATES 9,600
Slide 37: 2015 priorities: Execution and launch
2015 priorities: Execution and launch Guideline implementation in ACS Launch BRILINTA® / BRILIQUE™ into post MI Build the franchise – three world-class business units in coronary, stroke and PAD1 1 Peripheral Arterial Disease 37
Slide 38: Summary
Summary • Worldwide 2014 sales for BRILINTA® / BRILIQUE™ were $476m up 70%1 • Strong brand momentum in the United States continues • PEGASUS-TIMI 54 met its primary endpoint in both 60mg and 90mg doses • Upcoming SOCRATES study in stroke: From indication to franchise 1 At constant exchange rates 38
Slide 39: Questions & Answers
Questions & Answers Participants • Dr. Marc Sabatine, PEGASUS-TIMI 54 Primary Investigator (P.I.) • Tom Keith-Roach, BRILINTA® / BRILIQUE™ Task Force leader • Elisabeth Björk, Head of Global Medicines Development for Cardiovascular and Metabolic Disease • Marc Ditmarsch, BRILINTA® / BRILIQUE™ Clinic