Exjade ® (deferasirox; ICL670) NDA 21-882

1. DRA Introduction 8-3-05.ppt Exjade® (deferasirox; ICL670)NDA 21-882 United States Food and Drug AdministrationBlood Products Advisory Committee Meeting September 29, 2005

2. DRA Introduction 8-3-05.ppt Exjade® (deferasirox; ICL670)NDA 21-882Introduction PK Narang, PhD, FCPVice President, Global HeadDrug Regulatory Affairs—OncologyNovartis Pharmaceuticals Corporation

3. DRA Introduction 8-3-05.ppt ICL670Sponsor’s Agenda • Introduction PK Narang, PhD, FCPVice President, Drug Regulatory Affairs—OncologyNovartis Pharmaceuticals Corporation • Iron Overload: Complications and Need for Therapy John B. Porter, MDProfessor of HaematologyUniversity College, London, UK • Efficacy and Safety Peter Marks, MD, PhDSenior Director, Oncology Clinical DevelopmentNovartis Pharmaceuticals Corporation • Benefit/Risk Elliott Vichinsky, MDDirector, Hematology/OncologyChildren’s Hospital and Research Center at OaklandOakland, California

4. Iron OverloadOverview DRA Introduction 8-3-05.ppt • Transfusional iron overload • Serious complication in patients with transfusion- dependent anemias • Significant morbidity/mortality for inadequately chelated patients • Current “gold standard” therapy—Desferal® (Novartis) • Only approved/available iron chelator in US • Safe and effective (but parenteral) • Poor compliance a significant issue • Unmet medical need • Safe, effective agent with positive benefit/risk

5. ICL670Overview • A new class of tridentate iron chelator • Orally dosed • Drug kinetics support once-a-day dosing • Efficacy similar to Desferal® • Acceptable safety in adults and children

6. ICL670Proposed Indication DRA Introduction 8-3-05.ppt ICL670 is indicated for the treatment of chronic iron overload due to blood transfusions (transfusional hemosiderosis) in adult and pediatric patients (≥ 2 years old)

7. ICL670Regulatory History • IND submitted 1999 • Orphan designation 2002 • Fast-track status 2003 • SPA for 0107, 0108, 0109 2003 • NDA accepted in CMA-1 program Jan 2005 • NDA submission completed May 2005 • Priority review granted Jun 2005 DRA Introduction 8-3-05.ppt

8. ICL670Development Program Basis DRA Introduction 8-3-05.ppt • β-thalassemia as a model for documenting “effectiveness” • Largest prospective trials for an iron chelator • Efficacy may be applicable to other conditions of transfusional iron overload including sickle cell disease • Document safety in sickle cell disease and other rare anemias • Provide sufficient pediatric data in pivotal trials • 45% of patients

9. Key ICL670 Efficacy and Safety Trialsβ-thalassemia and Other Rare Anemias DRA Introduction 8-3-05.ppt Safety: Included study 106 (40 pediatric thalassemia patients). DFO = Desferal® (deferoxamine).

10. DRA Introduction 8-3-05.ppt ICL670Questions & Answers Consultants John Porter, MD Professor of Haematology University College, London Elliott Vichinsky, MD Director, Hematology/Oncology Children’s Hospital and Research Center at Oakland Alan Cohen, MD Physician-in-Chief and Medical Director, Thalassemia Program Children’s Hospital of Philadelphia Richard Larson, MD Professor of Medicine University of Chicago Raimund Hirschberg, MD Professor of Medicine Harbor-UCLA Medical Center Lloyd Fisher, PhD Professor Emeritus Department of Biostatistics University of Washington