1. 1 1 Zelnorm ® (tegaserod maleate) Advisory Committee Presentation Gastrointestinal Drugs July 14, 2004

2. 2 2 Introduction John Cutt, PhD Objectives of the Presentation  Proposed indication  Review Zelnorm ® Phase III clinical trial information  Review postmarketing safety data Objectives of the Presentation  Proposed indication  Review Zelnorm ® Phase III clinical trial information  Review postmarketing safety data

3. 3 3 Introduction (continued) John Cutt, PhD  Activity of tegaserod in GI tract  Clinical development program for chronic constipation  Zelnorm experience in clinical studies  Worldwide experience With Zelnorm  Conclusions  Agenda, speakers, and consultants  Activity of tegaserod in GI tract  Clinical development program for chronic constipation  Zelnorm experience in clinical studies  Worldwide experience With Zelnorm  Conclusions  Agenda, speakers, and consultants

4. 4 4 Unmet Need Charlene Prather, MD Division of Gastroenterology and Hepatology St. Louis University School of Medicine External Presenter Division of Gastroenterology and Hepatology St. Louis University School of Medicine External Presenter

5. 5 5 Efficacy and Safety in Chronic Constipation Eslie Dennis, MD Novartis Senior Medical Director, Gastroenterology Background  Tegaserod—Mechanism of action  Rationale for use of Zelnorm ® in the treatment of chronic constipation Phase III chronic constipation studies  Pivotal Studies E2301, 2302  Study Objectives Background  Tegaserod—Mechanism of action  Rationale for use of Zelnorm ® in the treatment of chronic constipation Phase III chronic constipation studies  Pivotal Studies E2301, 2302  Study Objectives

6. 6 6 Efficacy and Safety in Chronic Constipation (continued) Eslie Dennis, MD, Senior Medical Director Studies E2301, E2301E, E2302  Study design  Inclusion and exclusion criteria  Patient disposition  Demographic information and constipation symptoms prior to treatment Studies E2301, E2301E, E2302  Study design  Inclusion and exclusion criteria  Patient disposition  Demographic information and constipation symptoms prior to treatment

7. 7 7 Efficacy and Safety in Chronic Constipation (continued) Eslie Dennis, MD, Senior Medical Director Results  Primary efficacy variable, responder = increase of > 1 CSBM, Wk 1-4  Secondary efficacy variable, responder = increase of > 1 CSBM, Wk 1-12  Weekly responder rate and complete spontaneous bowel movements  Further a priori secondary variables –Satisfaction with bowel habits, stool form, straining Results  Primary efficacy variable, responder = increase of > 1 CSBM, Wk 1-4  Secondary efficacy variable, responder = increase of > 1 CSBM, Wk 1-12  Weekly responder rate and complete spontaneous bowel movements  Further a priori secondary variables –Satisfaction with bowel habits, stool form, straining

8. 8 8 Efficacy and Safety in Chronic Constipation (continued) Eslie Dennis, MD, Senior Medical Director  Additional analyses –Responder = ≥ 3 CSBM/wk during wk 1 – 4 –Responder = ≥ 3 CSBM/wk during wk 1 - 12 –Primary efficacy variable Responders by baseline bowel movements per wk Responders by subgroup Patients without IBS-like features  Efficacy in chronic constipation—summary  Additional analyses –Responder = ≥ 3 CSBM/wk during wk 1 – 4 –Responder = ≥ 3 CSBM/wk during wk 1 - 12 –Primary efficacy variable Responders by baseline bowel movements per wk Responders by subgroup Patients without IBS-like features  Efficacy in chronic constipation—summary

9. 9 9 Efficacy and Safety in Chronic Constipation (continued) Eslie Dennis, MD, Senior Medical Director Safety in Chronic Constipation—12-wk safety profile  Exposure  Most frequent adverse events  Most frequent leading to discontinuation  Diarrhea –Evaluation and management –No clinically significant consequences  Serious adverse events  Laboratory evaluations  Summary of ECG abnormalities and QTc intervals  Abdominal and pelvic surgeries Safety in Chronic Constipation—12-wk safety profile  Exposure  Most frequent adverse events  Most frequent leading to discontinuation  Diarrhea –Evaluation and management –No clinically significant consequences  Serious adverse events  Laboratory evaluations  Summary of ECG abnormalities and QTc intervals  Abdominal and pelvic surgeries

10. 10 Efficacy and Safety in Chronic Constipation (continued) Eslie Dennis, MD, Senior Medical Director Long-term safety profile (16 months)  Studies E2301, E2301E1  Adverse events >5% Conclusions Proposed Indication Long-term safety profile (16 months)  Studies E2301, E2301E1  Adverse events >5% Conclusions Proposed Indication

11. 11 Safety Overview (continued) Bo Joelsson Head GI Clinical Research and Development  Safety data — CC sNDA versus IBS-C NDA  Summary of patients treated in clinical trials and postmarketing  Serious adverse events in overall clinical experience  Safety data — CC sNDA versus IBS-C NDA  Summary of patients treated in clinical trials and postmarketing  Serious adverse events in overall clinical experience

12. 12 Safety Overview (continued) Bo Joelsson Head GI Clinical Research and Development Special Safety Topics Experience in Clinical Trials and Postmarketing  Diarrhea –Serious consequences  Rectal bleeding  Ischemic colitis  Cholecystectomies  Biliary tract disorders  Ovarian disease Special Safety Topics Experience in Clinical Trials and Postmarketing  Diarrhea –Serious consequences  Rectal bleeding  Ischemic colitis  Cholecystectomies  Biliary tract disorders  Ovarian disease

13. 13 Safety Overview (continued) Bo Joelsson, Novartis, Head GI Clinical Research and Development  Safety profile of Zelnorm  supports the use in patients with chronic constipation  Overall safety conclusions  Safety profile of Zelnorm  supports the use in patients with chronic constipation  Overall safety conclusions

14. 14 Benefit/Risk Philip Schoenfeld, MD, MSEd, MSc (Epi) Assistant Professor of Medicine University of Michigan School of Medicine External presenter Assistant Professor of Medicine University of Michigan School of Medicine External presenter