EXUBERA®(insulin [rDNA origin] powder

for inhalation)

Endocrinologic and Metabolic DrugsAdvisory Committee Meeting

September 8, 2005Dr. Neville Jackson

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Agenda

• Dr. Neville Jackson Introduction

• Dr. Anne Cropp Overview of Clinical Program

• Dr. William Cefalu Medical Need

• Dr. Neville Jackson Benefit and Managing the Risk

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Attending Experts

William Cefalu, MDProfessor and Chief, Division of Nutrition and Chronic DiseasesPennington Biomedical Research Center, LSU System

Tim Heise, MDChief Executive OfficerProfil Institute for Metabolical Research, Neuss, Germany

Edwin Fineberg, MDEmeritus Professor of Endocrinology and Metabolism Indiana University School of Medicine

Claudio Cobelli, PhDProfessor of Biomedical EngineeringUniversity of Padua, Italy

Joseph Brain, S.D.Professor of Environmental PhysiologyHarvard School of Public Health

Gary Williams, MDProfessor of PathologyNew York Medical College

Richard Ahrens, MDProfessor of Pediatrics, Pediatric Allergy and Pulmonary DivisionUniversity of Iowa

Marcia Testa, MPH, MPhil, PhDSenior Lecturer on BiostatisticsHarvard School of Public Health

Christine T Rathbun:

This needs to replace slide 3 after Mock III

Christine T Rathbun:

This needs to replace slide 3 after Mock III

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The Diabetes Epidemic

• Prevalence of diagnosed diabetes increased 40% from 4.9% in 1990 to 6.9% in 1999

• Estimated lifetime risk of developing diabetes for individuals born in 2000 is 32.8% for males and 38.5% for females

• If diagnosed at age 40, men will lose 11.6 years and 18.6 quality-adjusted-life-years. Women will lose 14.3 years and 22 quality-adjusted-life-years

Source: Narayan KMV, Boyle JP, Thompson TJ, et al. Lifetime Risk for Diabetes Mellitus in the United States JAMA. 2003;290:1884-90.

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Glycemic Control is Sub-optimal

• Insulin is the most effective treatment for diabetes and mandated for type 1 patients

• 67% of type 2 diabetes patients in United States are not achieving target glycemic control

• Insulin therapy is initiated too late in type 2 diabetes patients

• Intensive insulin therapy is underutilized in both type 1 and type 2 diabetes patients

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Video

Video Describing the Inhaler and How to Use the Inhaler Shown

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Inhaled InsulinProposed Indication and Usage

• Treatment of adult patients with diabetes mellitus for the control of hyperglycemia

– Combination therapy with intermediate/ long-acting SC insulin or oral agents

– Monotherapy (type 2)

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Clinical Development Program

IND 43313 NDA EOP 2

Phase 2

Phase 3 Group I

1993 20051994 1995 1996 1997 1998 1999 20042003200220012000

Phase 1

102 103 104

1036 102 E 103 E 104 E

Phase 1 Studies

Developmental

1001/1002

106 108 110

107 109 1009

111

1026 1027

1022 1029

1017

1028 1030

Phase 1 Studies Final Formulation

FDA Interactions Pre-NDA

Phase 3 Group II

Phase 3b

Exploratory

Efficacy

Long-term Safety

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Assessment of Pulmonary Function

• > 43,000 PFT measurements performed in > 4000 adult subjects

• Characterized PFT changes and reversibility in short- and long-term studies

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The Inhaled Insulin Clinical Development Program

• Efficacious as short-acting SC insulin

• Provides long-term glycemic control

• More patients preferred INH to previous therapy

• Safety profile characterized– Well tolerated, hypoglycemia comparable to injected insulin– Insulin antibodies– Small, early, non-progressive, reversible declines in FEV1 and

DLco• Mechanism unknown but under continued exploration

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Agenda

• Dr. Neville Jackson Introduction

• Dr. Anne Cropp Overview of Clinical Program

• Dr. William Cefalu Medical Need

• Dr. Neville Jackson Benefit and Managing the Risk