EXUBERA® (insulin [rDNA origin] powder for inhalation) Endocrinologic and Metabolic Drugs Advisory Committee Meeting September 8, 2005 Dr. Neville Jackson

2 Agenda Dr. Neville Jackson Introduction Dr. Anne Cropp Overview of Clinical Program Dr. William Cefalu Medical Need Dr. Neville JacksonBenefit and Managing the Risk

3 Attending Experts William Cefalu, MD Professor and Chief, Division of Nutrition and Chronic Diseases Pennington Biomedical Research Center, LSU System Tim Heise, MD Chief Executive Officer Profil Institute for Metabolical Research, Neuss, Germany Edwin Fineberg, MD Emeritus Professor of Endocrinology and Metabolism Indiana University School of Medicine Claudio Cobelli, PhD Professor of Biomedical Engineering University of Padua, Italy Joseph Brain, S.D. Professor of Environmental Physiology Harvard School of Public Health Gary Williams, MD Professor of Pathology New York Medical College Richard Ahrens, MD Professor of Pediatrics, Pediatric Allergy and Pulmonary Division University of Iowa Marcia Testa, MPH, MPhil, PhD Senior Lecturer on Biostatistics Harvard 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

4 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:

5 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

6 Video Video Describing the Inhaler and How to Use the Inhaler Shown

7 Inhaled Insulin Proposed 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)

8 Clinical Development Program IND 43313NDAEOP 2 Phase 2 Phase 3 Group I Phase E 103 E 104 E Phase 1 Studies Developmental 1001/ Phase 1 Studies Final Formulation FDA InteractionsPre- NDA Phase 3 Group II Phase 3b Exploratory Efficacy Long-term Safety

9 Assessment of Pulmonary Function > 43,000 PFT measurements performed in > 4000 adult subjects Characterized PFT changes and reversibility in short- and long-term studies

10 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 FEV 1 and DLco Mechanism unknown but under continued exploration

11 Agenda Dr. Neville Jackson Introduction Dr. Anne Cropp Overview of Clinical Program Dr. William Cefalu Medical Need Dr. Neville JacksonBenefit and Managing the Risk