CI-1 Exelon ® (rivastigmine) United States Food and Drug Administration Peripheral and Central Nervous System Drugs Advisory Committee May 17, 2006

CI-2 Exelon ® (rivastigmine) Introduction and Regulatory Overview Martina Struck, PhD Senior Associate Director Drug Regulatory Affairs Novartis Pharmaceuticals Corporation

CI-3 Exelon ® (rivastigmine) in Alzheimer’s Disease  Exelon is a slowly reversible cholinesterase inhibitor  Original New Drug Application – Approved April 21, 2000, in US – Mild to moderate dementia of the Alzheimer’s type (AD) Associated with cholinergic deficit – Approved in > 80 countries

CI-4 Registration Studies Supporting Current Indication of AD  Two randomized, double-blind, placebo- controlled studies – US 26-wk study (N = 699) – Global 26-wk study (N = 725)  To date, 2.1 million patient-years of postmarketing exposure

CI-5 Exelon ® (rivastigmine) in PDD  Parkinson’s disease dementia – Associated with cholinergic deficit – No approved treatment—unmet medical need  Supplemental New Drug Application – Filed Aug 31, 2005, in US – Proposed indication: Mild to moderate dementia associated with Parkinson’s disease – Approvals in 39 countries (Feb 2006 in EU)

CI-6 Well-Controlled Study for Additional Indication of PDD  EXPRESS Study – 24-wk, randomized, multi-center, double- blind, placebo-controlled study with 24-wk open-label extension – Met both primary endpoints Cognition: ADAS-cog Global assessment: ADCS-CGIC – Most secondary endpoints such as activities of daily living, executive function, attention, and behavior are statistically significant

CI-7 Key Interactions With the FDA on PDD  Dec 2001 and April 2004: Initial communication with FDA – Define dementia in PD without ambiguity, using criteria that have wide acceptance and are both valid and reliable – Delineate how patients with this entity differ from those with mild to moderate AD, to whom the currently approved claim for Exelon applies  Jan 2005:Submitted “white paper” on diagnosing PDD and distinguishing it from AD  May 2005: Meeting with FDA  Aug 2005:sNDA submitted

CI-8 Objectives of Novartis Presentations  To demonstrate that PDD is a distinct entity from AD and that PDD can be diagnosed using current clinical tools  To demonstrate that the results from the EXPRESS study support the efficacy and safety of Exelon in the treatment of PDD and that these results are adequate to support the proposed indication

CI-9 Agenda Introduction and Regulatory Overview Martina Struck, PhD Novartis Pharmaceuticals Corporation East Hanover, NJ, USA Neuropathology of Parkinson’s Disease Dementia James B. Leverenz, MD University of Washington Seattle, WA, USA PDD: A Clinical PerspectiveHoward Feldman, MDCM, FRCP(C) University of British Columbia Vancouver, British Columbia, CA Summary of Neuropathological and Clinical Features of PDD Clive Ballard, MD Institute of Psychiatry King’s College, London, UK

CI-10 Agenda Rationale for Indication of PDD and Study Design Roger Lane, MD, MPH Novartis Pharmaceuticals Corporation East Hanover, NJ, USA EXPRESS Study ResultsSibel Tekin, MD Novartis Pharmaceuticals Corporation East Hanover, NJ, USA Benefit-Risk AssessmentMurat Emre, MD Istanbul Faculty of Medicine Istanbul, Turkey Regulatory Considerations: PDD Indication for Exelon Martina Struck, PhD Novartis Pharmaceuticals Corporation East Hanover, NJ, USA

CI-11 Additional Consultants to Novartis Philip D. Harvey, PhDProfessor of Psychiatry Department of Psychiatry Mount Sinai School of Medicine New York, NY, USA Howard I. Hurtig, MDProfessor and Vice Chair Department of Neurology University of Pennsylvania Health System Philadelphia, PA, USA Robert Woolson, PhDProfessor Department of Biostatistics, Bioinformatics, and Epidemiology Medical University of South Carolina Charleston, SC, USA