Astrazeneca Plc · LSE:AZN
Astrazeneca — American Heart Association Scientific Sessions 2018
35 slides from Astrazeneca's conference presentation, Nov 12, 2018
Slide 1: American Heart Association Scientific Sessions 2018
American Heart Association Scientific Sessions 2018 Investor science conference call 12 November 2018
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: Speakers
Speakers Stephen D. Wiviott, MD, Elisabeth Björk FACC Vice President, Head of CVRM, Senior Investigator, TIMI Study Global Medicines Development Group Mark Mallon Klaus Hinterding Executive Vice President, Global Medicine Leader, Oral Global Products & Portfolio Diabetes Franchise Strategy, Global M
Slide 4: Agenda
Agenda Introduction DECLARE-TIMI 58 trial Farxiga perspective Q&As 4
Slide 5: DECLARE-TIMI 58
DECLARE — TIMI 58 Stephen D. Wiviott, MD for the DECLARE — TIMI 58 Investigators American Heart Association, Scientific Sessions November 10, 2018 BRIGHAM HEALTH BRIGHAM AND. HARVARD MEDICAL SCHOOL WOMEN'S HOSPITAL TEACHING HOSPITAL
Slide 6: Background
o> RE Background ¢ * Patients with type 2 DM are at high risk for development of atherosclerotic CV events and heart failure. * Dapagliflozin is a selective SGLT2 inhibitor which blocks glucose and sodium resorption in the kidney, and thereby | blood sugar, BP & weight. + Prior CV outcomes trials wi
Slide 7: Trial Design
Trial Design 17,160 with Type 2 DM Established CV Disease (6974) or Multiple Risk Factors (10186) DAPAGLIFLOZIN 10 mg RANDOMIZE 1:1 DOUBLE BLIND DAILY All other DM Rx per treating MD PLACEBO SRIGHAM HEALTH BRIGHAM AND WOMEN'S HOSPITAL In Person Q6 mo/ Follow-up visits telephone Q 3 mo DURATION EVENT
Slide 8: DECLARE Enrollment Criteria
» RECLARE Enrollment Criteria ¢ 58 Diagnosis of T2DM, HbA1c 6.5-12%, CrCl 260 ml/min AND Established ASCVD (Secondary prevention) Ischemic heart disease Cerebrovascular disease Peripheral Artery Disease Or Multiple risk factors for ASCVD (Primary prevention) Men > 55 yrs and women > 60 yrs with at l
Slide 9: DECLARE Analytic Plan
DECLARE Analytic Plan @ MACE Non-inferiority (Upper Bound Cl <1.3): 1-sided @ = 0.023 If non-inferior .... Superiority for Dual Primary Efficacy Endpoints (MACE & CVD/HHF) test each simultaneously with 2-sided a= 0.0231 if either significant, may recycle a to test other at 0.0462 If both significant
Slide 10: 17,160 patients
10 17,160 patients randomized at 882 sites, 33 countries between 5/2013-6/2015 = Lay ;public of Korea 357 ——Japan Spain: 195 ge Tai 95 ~ ; —Taiwan Se Mtaly:155 Ho Philippines t ENS 335 7 BRIGHAM HEALTH : BRIGHAM AND. HARVARD MEDICAL SCHOOL WOMEN'S HOSPITAL, TEACHING HOSPITAL
Slide 11: Follow-up
» Follow-up DECLARE Teas Randomized 17,160 patients Established ASCVD (6,974), MRF (10,186) Dapagliflozin Placebo (N=8582) (N=8578) Follow-up median 4.2 yr (IQR 3.9-4.4) Se A 1559 patients experienced MACE 913 experienced CVD/HHF T T Premature perm. drug discontinuation ReMi 6.2%/yr Withdrew consent
Slide 12: Baseline Characteristics
» Baseline Characteristics ¢ DECLARE a N = 17160 64 (7) Female Sex (%| 37 BMI, Mean (SD) 32 (6) Duration of T2DM, yrs, Median (IQR) 11 (6, 16) HbAic (%), Mean (SD) 8.3 (1.2) eGFR (CKD-EP!), Mean (SD) 85 (16) Region (%): North America 32 Europe 44 Latin America Ed: Asia Pacific 13 Established CV Dise
Slide 13: Baseline Characteristics: Medication Use
13 D Baseline Characteristics: — Medication Use ) #20 gm Full Trial Cohort N=17160 = [insuin a1 e 7 ; f si 53 75 DEER ory P=NS for all between treatment arm comparisons WOMENS HOSPITAL Teaco nosPtTaL
Slide 14: Cardiovascular Risk Factors
» Cardiovascular Risk Factors RECLARE HbA1c Weight LSM Difference 0.42% (95% Cl 0.40-0.45) LSM Difference 1.8 kg (95% Cl 1.7-2.0) ——~ Dapagliflozin—— Placebo Asa) 3 ass 82 82 eo y 9 Zr 77 76 75 BL 6mos 12 mos 24 mos 36 mos 48 mos BL 6 mos 12mos 24 mos 36 mos 48 mos All P-values (except BL) <0.001 Al
Slide 15: Cardiovascular Risk Factors
» Cardiovascular Risk Factors RECLARE SBP DBP LSM Difference 2.7 mmHg (95% Cl 2.4-3.0) LSM Difference 0.7mmHg (95% Cl 0.6-0.9) —— Dapagliflozin—— Placebo Cix6 O79 135 135 135 135 78) i. ; 76) 132 75) BL 6 mos 12 mos 24 mos 36 mos 48mos BL 6 mos 12mos 24 mos 36 mos 48 mos All P-values (except BL) <0.
Slide 16: Primary Endpoints
16 »D Primary Endpoints ¢ DECLARE Engst Bio Caananct CVD/HHF MACE 4.9% vs 5.8% 8.8% vs 9.4% HR 0.83 (0.73-0.95) HR 0.93 (0.84-1.03) P(Superiority) 0.005 P(Noninferiority) <0.001 ow 10% P(Superiority) 0.17 ~ | a ln A f Zw - i , i wo Ml Oe te en we SCS”*SCSCR GGG (owt ae ae Analysis time (days) Analyv
Slide 17: Secondary Endpoints
»D Secondary Endpoints ¢ DECLARE oa Bato Croatia Renal Composite EP All-Cause Mortality 40%) eGFR, ESRD, Renal or CV death 4.3% vs. 5.6% 6.2% vs 6.6% HR 0.76 (0.67-0.87) HR 0.93 (0.82-1.04) oy P<0.001 m4 P=0.20 4 3 Ree 5 i me La T r , T T T om oe eee ee eee 0 Wo Swe taw Analyss time (days) ‘Analysis
Slide 18: Endpoints and Components
18 oc ee Endpoints and Components Dapagliflozin Placebo rate/1000 —_—rate/1000 Pp ‘ CV death/HHF 12.2 14.7 0.83 (0.73-0.95) ent 0.005" MACE 22.6 24.2 0.93 (0.84-1.03) ren oo" 40% decrease in eGFR to <60 mi/min/m2, 10.8 141 0.76 (0.67-0.87) ont ESRD, or renal or CV death All-cause death 15.1 16.4 0.9
Slide 19: Primary Efficacy Endpoints by Presence of ASCVD vs MRF
D Primary Efficacy Endpoints ¥ RécLARE by Presence of ASCVD vs MRF Dapagliflozin Placebo Events per Events per Hazard Ratio P value for Outcomes 1000 ptyears 1000 pt years (95% Cl) interaction CV death/HHF 12.2 14.7 0.83 (0.73-0.95) — 0.99 ASCVD 19.9 23.9 0.83 (0.71-0.98) re—| MRF 7.0 8.4 0.84 (0.67
Slide 20: Effect on CVD/HHF in Key Subgroups
Effect on CVD/HHF in Key Subgroups CVD/HHF Dapagliflozin Placebo Hazard Ratio (95% Cl) HR (95%-Cl) —-P- Value for n\N n\N Interaction Total Cohort 41718582 496/8578 —_—— 0.83 (0.73-0.95) Risk Group i 0.99 ASCVD 27213474 — 325/3500 —e—_| 0.83 (0.71-0.98) MRF 145/5108 171/5078 -—e—H 0.84 (0.67-1.04) H
Slide 21: Key Safety Events
21 o> RE Key Safety Events pti Bo Canasta Dapagliflozin| Placebo Between Group Comparison reatment emergent SAE reatment emergent AE leading to d Major Hypoglycemia Diabetic Ketoacidosis* (DKA) Amputation Acute Kidney Injury Symptoms of volume depletion enital infection (SAE, DAE) Urinary tract infe
Slide 22: Summary
» Summary @ DECLARE Tas In DECLARE — TIMI 58, the largest SGLT2i trial, which included a broad representation of 1° and 2° prevention patients: * Dapagliflozin reduced CVD/HHF, was safe with regard to MACE and appeared to reduce renal events * CVD/HHF was consistent regardless of baseline ASCVD or H
Slide 23: Meta-Analysis of CVOTs: MACE by Presence of ASCVD
D Meta-Analysis of CVOTs: pectare MACE by Presence of ASCVD Treatment Placebo MACE Events per _—_ Events per HR [95% Cl] 1000 pt-yrs_ 1000 pt-yrs Atherosclerotic Cardiovascular Disease: EMPA-REG OUTCOME 37.4 43.9 ee 0.86 (0.74, 0.99} CANVAS Program 344 413 eH 0.82 (0.72, 0.95} DECLARE-TIMI 58 36.8 4
Slide 24: Meta-Analysis of CVOTs: CVD/HHF by Presence of ASCVD
D Meta-Analysis of CVOTs: ¥ psceareCVD/HHF by Presence of ASCVD Treatment Placebo CVD/HHF Events per _—_ Events per HR [95% Cl] 1000 pt-yrs_ _ 1000 pt-yrs Atherosclerotic Cardiovascular Disease: EMPA-REG OUTCOME 19.7 30.1 —— i 0.66 (0.55, 0.79} CANVAS Program 21 274 —s— 0.77 (0.65, 0.92} DECLARE-TIM
Slide 25: Conclusions
25 » Conclusions @ DECLARE Tas Now with the context of 3 large CVOTs: * SGLT2i have moderate benefits on atherosclerotic MACE that appear confined to those with established ASCVD * SGLT2i have robust effects on reducing the risk of heart failure and renal outcomes which do not appear dependent on ba
Slide 26: Additional Information
26 » Additional Information RECEARE ORIGINAL ARTICLE 62) th NEW ENGLAND OURNAL of MEDICINE a . : J g Dapagliflozin and Cardiovascular Outcomes S.D.W MG. S D.K. McGui P.A. Johansson, A.M. L SGLT2 inhibitors for primary and secondary prevention THE LANCET of cardiovascular and renal outcomes in type 2
Slide 27: Agenda
Agenda Introduction DECLARE-TIMI 58 trial Farxiga perspective Q&As 27
Slide 28: Farxiga: steady growth five years into launch
Farxiga: steady growth five years into launch Market leader by volume in the fastest-growing class Farxiga SGLT2 inhibitors is the fastest- $m global sales growing non-insulin antidiabetic class (global volume, days of therapy) Absolute values at actual exchange rates. Source: IQVIA, pharmacy sales,
Slide 29: Farxiga: opportunity to move into earlier use
Farxiga: opportunity to move into earlier use Meaningful CV benefit with opportunity for early use USA Germany Japan % of new patients % of new patients % of new patients Source: IQVIA APLD, patients starting therapy in June to August 2017 and tracking until July 2018. Source: IQVIA LRx, SGLT2 use,
Slide 30: Farxiga: potential in Emerging Markets
Farxiga: potential in Emerging Markets Potential to leverage AstraZeneca’s presence Top-ten countries of Example: in Brazil, Farxiga is the largest $m adults with diabetes oral, innovative anti-diabetic medicine SGLT-2 Competitor SGLT-2 Competitor 1 family share 2 family share DPP-IV competitor DPP-
Slide 31: Farxiga: heart failure remains a large unmet need
Farxiga: heart failure remains a large unmet need Very frequent T2D complication; no progress in a decade First CV event in type-2 diabetes patients Heart failure: (selected events, 6,137 events total) no reduction in mortality over the last decade PAD=peripheral arterial disease NFMI=non-fatal myoc
Slide 32: 2018 ADA-EASD T2D consensus report reflects emerging evidence from CV outcomes trials
New: 2018 ADA-EASD T2D consensus report reflects emerging evidence from CV outcomes trials DECLARE results were not yet available when consensus report was written CONSENSUS RECOMMENDATIONS • Patients with T2D who have established ASCVD: SGLT2 inhibitors or GLP-1 RAs with proven CV benefit recommend
Slide 33: Farxiga: lifecycle plans aim at extending benefits beyond type-2 diabetes
Farxiga: lifecycle plans aim at extending benefits beyond type-2 diabetes HFpEF Outcome Trial 33
Slide 34: Q&A
Q&A 34
Slide 35: Use of AstraZeneca conference call, webcast and presentation slides
Use of AstraZeneca conference call, webcast 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
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