CI-1 Zelnorm ® (tegaserod maleate) Gastrointestinal Drugs Advisory Committee Meeting July 14, 2004 Gastrointestinal Drugs Advisory Committee Meeting July 14, 2004 C

CI-2 Zelnorm ® (tegaserod maleate) Introduction John R. Cutt, PhD Executive Director Global Head, Gastrointestinal Group Drug Regulatory Affairs John R. Cutt, PhD Executive Director Global Head, Gastrointestinal Group Drug Regulatory Affairs C

CI-3 Objectives of Today’s Presentation  Review Zelnorm ® phase 3 clinical trial data in support of new indication:  Review postmarketing safety data  Review Zelnorm ® phase 3 clinical trial data in support of new indication:  Review postmarketing safety data C Zelnorm (tegaserod maleate) is indicated for the treatment of patients with chronic constipation and relief of associated symptoms of straining, hard or lumpy stools, and infrequent defecation

CI-4 Zelnorm ® (tegaserod maleate) Activity in GI Tract  5-HT 4 receptor partial agonist with affinity for 5-HT 4 receptors in the GI tract  Pharmacologic activity in GI tract –Enhances intestinal motility –Stimulates intestinal secretion –Inhibits visceral sensitivity  Demonstrated to improve constipation symptoms in IBS-C patients  5-HT 4 receptor partial agonist with affinity for 5-HT 4 receptors in the GI tract  Pharmacologic activity in GI tract –Enhances intestinal motility –Stimulates intestinal secretion –Inhibits visceral sensitivity  Demonstrated to improve constipation symptoms in IBS-C patients GI = Gastrointestinal; IBS-C = Irritable Bowel Syndrome with Constipation  Hypothesis: Zelnorm offers a unique mechanism of action to treat patients suffering from chronic constipation

CI-5 Clinical Development Program for Chronic Constipation  2 randomized, placebo-controlled pivotal trials –12-wk blinded treatment to assess efficacy and safety –2 mg and 6 mg BID versus placebo –2612 patients with chronic constipation –1 trial included 13-month extension phase to assess long-term safety –1 trial included a 4 week withdrawal period  2 randomized, placebo-controlled pivotal trials –12-wk blinded treatment to assess efficacy and safety –2 mg and 6 mg BID versus placebo –2612 patients with chronic constipation –1 trial included 13-month extension phase to assess long-term safety –1 trial included a 4 week withdrawal period C

CI-6 Zelnorm ® Experience in Clinical Studies  July 24, 2002 –FDA approval for the short-term treatment of women with irritable bowel syndrome whose primary bowel symptom is constipation (6 mg BID) –Efficacy, safety, and tolerability had been documented in 5319 Zelnorm-treated patients in clinical trials  July 14, 2004 –> 11,600 patients have received Zelnorm in clinical trials –3456 patient-yr exposure  July 24, 2002 –FDA approval for the short-term treatment of women with irritable bowel syndrome whose primary bowel symptom is constipation (6 mg BID) –Efficacy, safety, and tolerability had been documented in 5319 Zelnorm-treated patients in clinical trials  July 14, 2004 –> 11,600 patients have received Zelnorm in clinical trials –3456 patient-yr exposure

CI-7 Worldwide Experience With Zelnorm ®  Zelnorm approvals –56 countries for patients with irritable bowel syndrome with constipation –10 countries for patients with chronic constipation  First made available to patients in January 2001 –Over 3 years in clinical practice –~ 3 million patients treated globally ~ 2 million patients treated in the US  Zelnorm approvals –56 countries for patients with irritable bowel syndrome with constipation –10 countries for patients with chronic constipation  First made available to patients in January 2001 –Over 3 years in clinical practice –~ 3 million patients treated globally ~ 2 million patients treated in the US  An estimated 362,000 patient-yr of postmarketing experience supports a positive safety profile

CI-8 Conclusion  Zelnorm ® 6 mg BID is efficacious and safe for the treatment of patients with multiple symptoms of chronic constipation  Clinical data support the proposed Zelnorm (tegaserod maleate) is indicated for the treatment of patients with chronic constipation and relief of associated symptoms of straining, hard or lumpy stools, and infrequent defecation  Zelnorm ® 6 mg BID is efficacious and safe for the treatment of patients with multiple symptoms of chronic constipation  Clinical data support the proposed Zelnorm (tegaserod maleate) is indicated for the treatment of patients with chronic constipation and relief of associated symptoms of straining, hard or lumpy stools, and infrequent defecation C

CI-9 Agenda and Today’s Speakers Eslie Dennis, MD Clinical Development and Medical Affairs, Novartis Zelnorm ® (tegaserod maleate): Efficacy and Safety in Chronic Constipation Charlene Prather, MD Associate Professor of Internal Medicine St. Louis University Chronic Constipation: An Unresolved Problem for Many Patients Bo Joelsson, MD, PhD Clinical Research and Development, Novartis Zelnorm: Safety Overview Philip Schoenfeld, MD, MSEd, MSc (Epi) Chief, Division of Gastroenterology Ann Arbor VAMC U. of Michigan School of Medicine Zelnorm: Benefit/Risk Assessment

CI-10 Consultants Felix M. Arellano, MD, FISPE Risk Management Resources, LLC Califon, NJ Gary Koch, PhD Department of Biostatistics University of North Carolina at Chapel Hill David Lieberman, MD Chief, Division of Gastroenterology Oregon Health and Science University Walter Peterson, MD Department of Internal Medicine University of Texas Southwestern Medical Center