KYNAPID

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KYNAPID (vernakalant hydrochloride
injection)Cardiovascular and Renal
DrugsAdvisory Committee

• Astellas Pharma US, Inc.
• December 11, 2007

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Introduction

• Donald Raineri, Pharm.D.
• Senior Director, Regulatory AffairsAstellas
  Pharma US, Inc.

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Vernakalant Injection

• Proposed Indication Vernakalant injection is
  indicated for the rapid conversion of atrial
  fibrillation of 7 days duration to sinus
  rhythm.
• Dosage and Administration The initial infusion
  of vernakalant injection is 3 mg/kg infused over
  10 minutes. If conversion to sinus rhythm does
  not occur within 15 minutes after the end of the
  initial infusion, a second 10-minute infusion of
  2 mg/kg may be administered.

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Key Attributes ofVernakalant Injection

• Effective and rapid conversion of AF to sinus
  rhythm with reduction of AF symptoms
• Durability of sinus rhythm out to 24 hours
• Concomitant use with rate or rhythm control
  medications without affecting safety or efficacy
• Well-characterized safety profile
• Favorable risk-benefit profile
• An important treatment alternative for patients
  with symptomatic atrial fibrillation

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Todays Agenda
Introduction Donald Raineri, Pharm.D. Sr. Director, Regulatory Affairs, Astellas
Clinical Overview of Atrial Fibrillation Edward L.C. Pritchett, M.D. Consulting Professor of Medicine Duke University Medical Center
Mechanism of Action Greg Beatch, Ph.D.Vice President, Scientific Affairs, Cardiome
Toxicology Clinical Pharmacology James Keirns, Ph.D. Sr. Director, Biopharmaceutical Sciences, Astellas
Clinical Efficacy Safety and Risk Management Therese M. Kitt, M.D. Sr. Medical Director, Medical Sciences, Astellas
Risk/Benefit Summary Jeremy N. Ruskin, M.D. Director, Cardiac Arrhythmia Services Massachusetts General Hospital
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Expert Consultants

• David Fedida, M.D., Ph.D.
• Professor and Associate Head, Anesthesiology,
  Pharmacology and Therapeutics University of
  British Columbia
• Peter R. Kowey, M.D.
• President of the Main Line Health Heart Center
• William Wikoff Smith Chair in Cardiovascular
  Research
• Professor of Medicine and Clinical Pharmacology
• Jefferson Medical College
• Craig Pratt, M.D.
• Director, Coronary Intensive Care Unit
• The Methodist DeBakey Heart Center, The
  Methodist Hospital
• Edward L.C. Pritchett, M.D.
• Consulting Professor of Medicine
• Duke University Medical Center
• Jeremy N. Ruskin, M.D.
• Director, Cardiac Arrhythmia Services
• Massachusetts General Hospital

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Astellas and Cardiome Experts

• Astellas Representatives
• Marlowe Schneidkraut, Ph.D., DABTAssociate
  Director, Toxicology
• Jeen Liu, Ph.D.Director, Clinical Statistics
• Cardiome Representative
• Garth Dickinson, M.D., FRCPCMedical Consultant
• Brian Mangal, MScDirector of Biostatistics