1. CI-1 ATACAND ® (candesartan cilexetil) Cardiovascular and Renal Drugs Advisory Committee Rockville, Maryland February 24, 2005 C

2. CI-2 ATACAND ® (candesartan cilexetil) Introduction Cindy M. Lancaster, MS, MBA, JD Director, Regulatory Affairs AstraZeneca LP C

3. CI-3 Sponsor Representatives Cindy M. Lancaster, MS, MBA, JD Director, Regulatory Affairs James Hainer, MD, MPH Senior Director, Clinical Research Eric Michelson, MD Senior Director, Clinical Research Howard Hutchinson, MD Vice President, Clinical Research Richard Caplan, PhD Senior Statistical Scientist Bertil Olofsson, PhD Senior Statistical Scientist

4. CI-4 External Advisors Marc A. Pfeffer, MD, PhDBrigham and Women’s Hospital Interim Chairman of Medicine Co-Chair CHARM Executive Committee James B. Young, MDCleveland Clinic Foundation Chairman of Medicine CHARM US National Leader John J.V. McMurray, MDProfessor of Medical Cardiology University of Glasgow Member, CHARM Executive Committee Principal Investigator, CHARM Added Trial Christopher B. Granger, MDDirector, Cardiac Care Unit Duke University Medical Center Member, CHARM Executive Committee Principal Investigator, CHARM Alternative Trial Mark E. Dunlap, MDDirector, Cardiology Research Department of Medicine Louis Stokes VA Medical Center, Case Western Reserve University CHARM US National Leader

5. CI-5 External Advisors Julia Lewis, MDProfessor in the Division of Nephrology Department of Medicine Vanderbilt University Joseph McLaughlin, PhDInternational Epidemiology Institute President Epidemiology Consultant Richard Kronmal, PhDProfessor of Biostatistics University of Washington Charles Hennekens, MDUniversity of Miami School of Medicine Chair, CHARM Data and Safety Monitoring Board

6. CI-6 ATACAND ® (candesartan cilexetil) Heart Failure Regulatory History 1998199920002001200420022003199619972005 Pre-sNDA conference - 11/03 SH-AHS-0001 (RESOLVD) SH-AHS-0002 (SPICE) SH-AHS-0008 (High dose) End of phase II meeting - CHARM - 10/98 SH-AHS-0003/6/7 (CHARM) Approvable letter for CHARM Added - 12/28/04 sNDA submission - 06/04 CHARM Alternative - Approval granted for heart failure indication - 2/22/05 CHARM Added - Advisory Committee Meeting - 2/24/05

7. CI-7 CHARM Added n = 2548 LVEF ≤ 40% ACE inhibitor treated CHARM Alternative n = 2028 LVEF ≤ 40% ACE inhibitor intolerant CHARM Preserved Patients With Symptomatic CHF CHARM Program n = 3023 LVEF > 40% ACE inhibitor treated/not treated 3 component trials comparing candesartan to placebo Pooled CSR S 5.1 P 58, S 5.4.5 P 69-70, S 8.2 P 160 Primary endpoint for each trial: CV death or CHF hospitalization

8. CI-8 Primary Endpoint CV Death or CHF Hospitalization CHARM Program 0.60.70.80.91.01.11.2 CHARMPatients, n/N Alternative406/1015334/1013 Added538/1272483/1276 Preserved366/1509333/1514 Hazard ratio (95% CI) Candesartan better Placebo better

9. CI-9 Approval for Add-on Therapy or for Use Without an ACE Inhibitor Austria Belgium Denmark Finland Germany Greece Ireland Italy Latvia Luxemburg Mexico The Netherlands New Zealand Portugal Slovakia Spain Sweden UK

10. CI-10 Approved Labeling for Heart Failure Indications and Usage Section ATACAND ® is indicated for the treatment of heart failure (NYHA class II-IV and ejection fraction ≤ 40%) to reduce the risk of death from cardiovascular causes and reduce hospitalizations for heart failure C

11. CI-11 Approved Labeling for Heart Failure Clinical Trials Section The use of candesartan was supported by a second study (CHARM Added) of 2548 subjects with NYHA Class II-IV heart failure and ejection fraction ≤ 40% in which subjects were mostly on submaximal doses of ACE inhibitors. Together, in these studies, subjects on Atacand ® had a 15% lower risk of cardiovascular mortality (p = 0.005). In these studies, symptoms of heart failure as assessed by NYHA functional class were also improved (p < 0.001). C

12. CI-12 Current Regulatory Question CHARM Added Designed to allow investigators to optimize ACE inhibitor dose Demonstrated statistically significant and clinically important benefits when candesartan was added to evidence-based doses of ACE inhibitors FDA’s central question Does “CHARM Added provide compelling evidence that candesartan should, under some circumstances, be recommended for use in patients on an ACE inhibitor?”

13. CI-13 Presentation Overview Background James B. Young, MD Cleveland Clinic Foundation  Rationale for use of an ARB in heart failure  ARBs and ACE inhibitors have distinct and complementary mechanisms  Candesartan has potentially beneficial effects when added to an ACE inhibitor John J.V. McMurray, MD University of Glasgow  Evidence-based dose of ACE inhibitor Efficacy Marc A. Pfeffer, MD, PhD Brigham and Women’s Hospital Boston  CHARM Added  FDA requested supplemental analyses— maximum ACE inhibitor dose Safety James W. Hainer, MD, MPH AstraZeneca LP  CHARM Added Benefit/Risk James B. Young, MD Cleveland Clinic Foundation  CHARM Added