ACAMPROSATE Lipha Pharmaceuticals, Inc. May 10, 2002 Psychopharmacologic Drugs Advisory Committee Meeting May 10, 2002 Psychopharmacologic Drugs Advisory Committee Meeting

ACAMPROSATE Introduction Anita M. Goodman, M.D. Executive Vice-President and COO Lipha Pharmaceuticals, Inc. Anita M. Goodman, M.D. Executive Vice-President and COO Lipha Pharmaceuticals, Inc.

ACAMPROSATE GI-3 The Toll of Alcohol Dependence  Over 8.1 million alcohol-dependent people in the United States  Economic cost: $185 billion per year  100,000 deaths per year  Over 8.1 million alcohol-dependent people in the United States  Economic cost: $185 billion per year  100,000 deaths per year From: Fuller, R.K., Gordis, E. Editorial: Naltrexone Treatment for Alcohol Dependence NEJM 345: , 2001

ACAMPROSATE GI-4 Pharmacotherapy and Alcoholism  Paucity of available approved medications –Disulfiram (aversive agent) –Naltrexone (opioid antagonist)  Lingering resistance to treatments other than psychotherapeutic  Lack of universally accepted outcome criteria  Paucity of available approved medications –Disulfiram (aversive agent) –Naltrexone (opioid antagonist)  Lingering resistance to treatments other than psychotherapeutic  Lack of universally accepted outcome criteria

ACAMPROSATE European Development Program and Current Registration Status Sylvie Chabac, M.D. International Project Manager LIPHA s.a.s. Lyon, France

ACAMPROSATE GI-6 Why Pivotal? Qualities of All Studies:  Study conducted by qualified investigators  Study conducted according to existent Good Clinical Practice standards  Study conducted according to specified protocol  Existent case report forms  Electronic data base Qualities of All Studies:  Study conducted by qualified investigators  Study conducted according to existent Good Clinical Practice standards  Study conducted according to specified protocol  Existent case report forms  Electronic data base Source: ISE Section

ACAMPROSATE GI-7 Why Pivotal? Additional Qualities of Selected Studies  Study centers still active, with accessible medical records and source documents (permitting site audit by FDA)  CROs still active  2 dosage levels Additional Qualities of Selected Studies  Study centers still active, with accessible medical records and source documents (permitting site audit by FDA)  CROs still active  2 dosage levels Source: ISE Section

ACAMPROSATE Acamprosate: Mechanism of Action, Preclinical Effects, and Pharmacokinetic Overview George F. Koob, Ph.D. Professor, Department of Neuropharmacology Director, Division of Neuropharmacology The Scripps Research Institute La Jolla, CA

ACAMPROSATE Efficacy Results from Three Pivotal Efficacy Trials Karl F. Mann, M.D. Professor and Chairman Department of Addictive Behaviour and Addiction Medicine Central Institute of Mental Health of Mannheim University of Heidelberg Mannheim, Germany

ACAMPROSATE Analysis of the US Study Results Barbara J. Mason, Ph.D. Professor, Department of Psychiatry and Behavioral Sciences Director, Division of Substance Abuse University of Miami School of Medicine Miami, FL

ACAMPROSATE GI-11 Acamprosate: Issues  Why were the efficacy results from the US trial inconclusive in contrast to the consistently positive European studies?  Were the methodologies in these trials appropriate?  Are alcohol dependent populations in Europe and the United States comparable?  Why were the efficacy results from the US trial inconclusive in contrast to the consistently positive European studies?  Were the methodologies in these trials appropriate?  Are alcohol dependent populations in Europe and the United States comparable?