TEGASEROD PROGRAM FUNCTIONAL DYSPEPSIA Sam O. Sue, MD VP/Clinic Research Development Global Medical Advisor East Hanover, NJ USA NOVARTIS PHARMACEUTICALS CORPORATION Advisory Board Meeting 01/24/03 (Version final) V4

Functional Dyspepsia Recurrent upper Abnominal Discomfort without identifiable cause Often meal related epigastric discomfortBloating, Early Satiety, Fullness 20 to 30% Gastro Consults Advisory Board Meeting 01/24/03 (Version final) V4

Tegaserod Mechanistic Properties Tegaserod accelerates Gastric Emptying - Volunteers Tegaserod normalizes delayed Gastric Emptying - FD Tegaserod improves post meal Gastric accommodation Merz, M. et al Clinical Pharmacology Report, Novartis oct 99 Earnest, D. et al submitted Gastro - DDW 2003 Jack, J. et al UEGW 2002 (references?) Advisory Board Meeting 01/24/03 (Version final) V4

Functional Dyspepsia Phase II Studies 4 DBPC dose finding studies (D2201-2204) Patient Population: FD > 3 months duration Treatment : 8 weeks Gastric emptying status 0.5 mg 2 mg 6 mg 12 mg NGE BID (D2202) x x x TID (D2204) x x x DGE (+NGE) BID (D2201) x x x TID (D2203) x x x Advisory Board Meeting 01/24/03 (Version final) V4

Touch-Tone Dyspepsia Assessment (IVRS) Daily (first week) and Weekly Study Design Tegaserod bid/tid Tegaserod bid/tid Screening Baseline Tegaserod bid/tid Placebo 1 week 2 weeks 8 weeks Endoscopy Scintigraphy Random- ization Touch-Tone Dyspepsia Assessment (IVRS) Daily Daily (first week) and Weekly Advisory Board Meeting 01/24/03 (Version final) V4

FD: Efficacy Assessments Primary: Satisfactory relief of meal related stomach problems (IVRS): Yes/No Daily (last week baseline, first week treatment) Weekly (remainder of treatment) Secondary: Daily severity of (4-pt scale, IVRS): early satiety, postprandial fullness, postprandial bloating in the stomach region, stomach pain, nausea, vomiting Quality of Life Generic (MOS SF-36) Disease specific (Nepean) Advisory Board Meeting 01/24/03 (Version final) V4

Secondary Efficacy Assessments Weekly: • most bothersome symptom Daily: • early satiety • postprandial fullness • postprandial bloating in the stomach region • nausea • epigastric/stomach pain • vomiting (yes/no) Daily discomfort scale 0 = none (not present) 1 = mild (awareness of the symptom but easily tolerated) 2 = moderate (discomfort sufficient to interfere with normal activities such as work and sleep) 3 = severe (incapacitating with inability to perform Advisory Board Meeting 01/24/03 (Version final) V4

Disease characteristics at Baseline Most bothersome symptoms (Pooled ITT) 40% 37% 35% 30% Postprandial bloating 25% 21% 19% Postprandial fullness Percent of patients 20% Epigastric/Stomach Pain 15% 10% 10% Early Satiety 10% 2% Nausea 5% Vomiting 0% Advisory Board Meeting 01/24/03 (Version final) V4

Responder Rates for Satisfactory Relief Responder: Satisfactory relief at least 50% or 75% of the weeks during treatment period 40%  5.6%  11.8% 30% * Responders (pooled ITT) 20% 10% 37.6% 40.6% 37.5% 35.3% 36.4% 26.3% 24.5% 31.9% 29.2% 24.8% 24.6% 21.7% 22.7% 10.9% 12.6% 13.8% 24.5% 14.6% 0% BID TID BID TID  50%  75% Placebo BID (n=125) T 0.5 mg bid (n=69) T 2 mg bid (n=120) T 6 mg bid (n=119) T 12 mg bid (n=55) Placebo TID (n=95) T 0.5 mg tid (n=94) T 2 mg tid (n=94) T 6 mg tid (n=89) Advisory Board Meeting 01/24/03 (Version final) V4

Gastric Retention (%) of Meal at 4 hours post meal (DGE-ITT) * “normal” gastric retention rate at 4 hours is 6.3% T24 T18 T12 T6 Placebo Advisory Board Meeting 01/24/03 (Version final) V4

Summary of Tolerability (D2201-2204) Most frequent adverse event is diarrhea Dose dependent increase in frequency irrespective of gastric emptying status Leading rarely to discontinuation, highest in 6 mg TID with 9% More frequent in males Diarrhea not well defined and frequency possibly overestimated Advisory Board Meeting 01/24/03 (Version final) V4

CONFIDENTIAL Conclusions Baseline severity and gastric emptying status were significant covariates for all symptoms. Other “less important” covariates include age and hp status. For fullness, satiety, and bloating, the medium doses, i.e. 2 tid, 6 bid and 6 tid showed positive treatment effects at most weeks. The best treatment effects were around 0.1 (improvement over placebo). “Baseline severity and gastric emptying status were significant covariates for all symptoms. Other “less important” covariates include age and hp status.” Advisory Board Meeting 01/24/03 (Version final) V4

Conclusions (cont.) Better treatment responses were observed in some patient subgroups, e.g. Female patients tended to be more responsive with medium doses for most symptoms; GE normal patients responded better at 6 mg bid while GE delayed responded better at 6 mg tid. Less severe patients responded better at 6 mg bid, but not at other doses. Advisory Board Meeting 01/24/03 (Version final) V4