1. Pramlintide Advisory Committee July 26, 2001 Symlin ® Amylin Pharmaceuticals New Drug Application (21-332) Advisory Committee Meeting Bethesda, Maryland (July 26, 2001) Advisory Committee Meeting Bethesda, Maryland (July 26, 2001) Center for Drug Evaluation and Research

2. Pramlintide Advisory Committee July 26, 2001 EFFICACY - Robert I Misbin, MD Type 1 diabetes Type 2 diabetes SAFETY - Dragos Roman, MD Hypoglycemia EFFICACY - Robert I Misbin, MD Type 1 diabetes Type 2 diabetes SAFETY - Dragos Roman, MD Hypoglycemia

3. Pramlintide Advisory Committee July 26, 2001 Type 1 Diabetes 8.2 8.9 8.8 8.9 9.0 8.9 8.9

4. Pramlintide Advisory Committee July 26, 2001 Trial 117 - Type 1 Diabetes Stable metabolic regimen HbA1c at least 8% at screening Patients to remain on their usual diet, type of insulin, insulin regimen and exercise regimen Stable metabolic regimen HbA1c at least 8% at screening Patients to remain on their usual diet, type of insulin, insulin regimen and exercise regimen

5. Pramlintide Advisory Committee July 26, 2001 TYPE 1 DIABETES TRIAL 117 Mean data at baseline –38 years old –16 years of diabetes –BMI 25 –HbA1c 9.0% –50 units insulin/day Mean data at baseline –38 years old –16 years of diabetes –BMI 25 –HbA1c 9.0% –50 units insulin/day

6. Pramlintide Advisory Committee July 26, 2001 American Diabetes Association Recommendations HbA1c <7% Goal of therapy HbA1c >8% “additional action suggested” HbA1c <7% Goal of therapy HbA1c >8% “additional action suggested”

7. Pramlintide Advisory Committee July 26, 2001 Trial 117 - Type 1 Diabetes Stable metabolic regimen HbA1c at least 8% at screening Patients to remain on their usual diet, type of insulin, insulin regimen and exercise regimen Stable metabolic regimen HbA1c at least 8% at screening Patients to remain on their usual diet, type of insulin, insulin regimen and exercise regimen

8. Pramlintide Advisory Committee July 26, 2001 Type 1 Diabetes Study 117

9. Pramlintide Advisory Committee July 26, 2001 Type 1 Diabetes - Trial 117 “Early Glycemic Responder” Subgroup Reduction in HbA1c at least 0.5% units at 4 weeks Show data at 4 and 26 weeks “Early Glycemic Responder” Subgroup Reduction in HbA1c at least 0.5% units at 4 weeks Show data at 4 and 26 weeks

10. Pramlintide Advisory Committee July 26, 2001 Early Glycemic Responders Study117

11. Pramlintide Advisory Committee July 26, 2001 Early Glycemic Responders 117

12. Pramlintide Advisory Committee July 26, 2001 Early Glycemic Responders 117

13. Pramlintide Advisory Committee July 26, 2001

14. Pramlintide Advisory Committee July 26, 2001 Pramlintide Treatment of Type 1 Diabetes 3-4 injections per day in addition to insulin More severe hypoglycemia than reducing HbA1c with insulin alone Weight loss relative to insulin alone 3-4 injections per day in addition to insulin More severe hypoglycemia than reducing HbA1c with insulin alone Weight loss relative to insulin alone

15. Pramlintide Advisory Committee July 26, 2001 Type 2 Diabetes

16. Pramlintide Advisory Committee July 26, 2001 TYPE 2 DIABETES TRIAL 123 Mean data at baseline –58 years old –13 years of diabetes –BMI 30.6 –HbA1c 9.4% –56 units insulin/day Mean data at baseline –58 years old –13 years of diabetes –BMI 30.6 –HbA1c 9.4% –56 units insulin/day

17. Pramlintide Advisory Committee July 26, 2001 Trial 123 - Type 2 Diabetes HbA1c at least 8% at screening Patients to remain on their usual diet, insulin regimen, and exercise regimen “changes in insulin doses were not encouraged in order to limit the impact of alterations in insulin dosing on glycemic control.” HbA1c at least 8% at screening Patients to remain on their usual diet, insulin regimen, and exercise regimen “changes in insulin doses were not encouraged in order to limit the impact of alterations in insulin dosing on glycemic control.”

18. Pramlintide Advisory Committee July 26, 2001 Type 2 Diabetes Study 123 ITT population

19. Pramlintide Advisory Committee July 26, 2001 Type 2 Diabetes Metformin Annals of Internal Medicine 1999; 131:185 - 0.9 Insulin + Metformin Insulin + Placebo

20. Pramlintide Advisory Committee July 26, 2001

21. Pramlintide Advisory Committee July 26, 2001 Type 2 Diabetes Study 123 ITT population

22. Pramlintide Advisory Committee July 26, 2001 SAFETY REVIEW Dr Dragos Roman