Joann L. Data, MD, PhD Senior VP, Regulatory Affairs & Quality Assurance Amylin Pharmaceuticals, Inc.

7/31/01


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Table of Contents

Joann L. Data, MD, PhD Senior VP, Regulatory Affairs & Quality Assurance Amylin Pharmaceuticals, Inc.

SYMLIN™ (Pramlintide Acetate)

SYMLIN Injection

Amylin’s Presentation

Consultants

Kenneth Polonsky, MD Adolphus Busch Professor of Medicine Chairman, Department of Medicine Washington University School of Medicine

A Century of Diabetes Care

Insulin Therapy Necessary When ?-Cell Fails

Lessons from the DCCT and UKPDS: Continuous Relationship Between Glycemia and Long-Term Complications

Lessons from the DCCT and UKPDS: Sustained Intensification of Therapy is Difficult

Insulin Therapy and Glycemic Control in Young, Insulin-Treated Patients

Lessons from the DCCT and UKPDS: Intervention Works, but is Difficult to Achieve

Our Ability to Achieve Tight Glycemic Control with Insulin Therapy is Limited by:

Barriers to Achieving Glycemic Targets with Insulin in Type 1 Diabetes: Severe Hypoglycemia

Barriers to Achieving Glycemic Targets with Insulin in Type 2 Diabetes: Hypoglycemia

Intensified Insulin Therapy Produces Weight Gain

Impact of Weight Gain on Cardiovascular Risk Factors Type 1 Patients on IIT (n=582), Stratified by Weight Change

Glucose Lowering Efficacy: Importance of Postprandial Hyperglycemia

Daily Log and Sensor Data (24 hrs)

Current Opportunity to Achieve Glycemic Goals

Andrew Young, MD PhD Vice President, Research Amylin Pharmaceuticals, Inc.

Pramlintide Pharmacology

Amylin: a Neuroendocrine Hormone

Amylin Binding/Receptors in Rat Brain

Hormonal Disturbances in Diabetes

Pramlintide: an Analog of Amylin

Three Fluxes Control Blood Glucose

Pramlintide Smoothes Glucose Profiles After Meals in Type 1 Diabetic Humans

Glucoregulatory Actions of Amylin

Pramlintide Suppresses Postprandial Glucagon Secretion

Amylin Inhibits Nutrient-Stimulated, But Not Hypoglycemia-Stimulated Glucagon Secretion in Rats

Pramlintide Does Not Affect Defenses Against Hypoglycemia in Humans

Glucoregulatory Actions of Amylin

Pramlintide Slows Gastric Emptying in Humans with Type 1 Diabetes

Gastric Actions of Amylin Over-ridden by Hypoglycemia in Rats

Amylin-Sensitive Neurons in Area Postrema are Almost All Glucose-Sensitive

Summary: Glucoregulatory Actions of Amylin/Pramlintide

Summary: Rationale for Pramlintide

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Pramlintide Indication

Pramlintide Population

Pramlintide Therapy

Number of Patients Included in Pramlintide Database

Duration of Exposure to Pramlintide All Studies, All Doses

Population Demographics Long-Term, Controlled Studies

Concomitant Medication Use

Pramlintide as Adjunctive Therapy to Insulin in Type 1 and Type 2 Diabetes Results in:

Pramlintide Therapy

Pramlintide Pharmacokinetic Profile Type 1 and Type 2 Diabetes

Addition of Pramlintide to Regular Insulin Therapy Improves Postprandial Glucose Control

Preprandial Addition of Pramlintide Improves Postprandial Glucose Control

Pramlintide Reduces Postprandial Glucose Concentrations in a Dose-Related Manner

Pramlintide Dose-Relationships

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Doses Selected for Phase 3 Studies

Phase 3 Clinical Trials

Study Design Considerations

General Approach to Pramlintide Phase 3 Clinical Studies

Approaches to Insulin Management

Insulin Use in Pramlintide Phase 3 Clinical Studies

Phase 3 Study Design Type 2 and Type 1 Diabetes

Pramlintide Therapy

Type 2 Diabetes Phase 3 Program

Summary of Pramlintide Effects Type 2, Recommended Dose

Pramlintide Phase 3 Studies Type 2 Diabetes HbA1c Effect for Total Population (ITT, 6 months)

Addition of Pramlintide to Insulin Reduces HbA1c in Type 2 Diabetes

Pramlintide Therapy Results in Greater Reduction in HbA1c Than Insulin Alone in Type 2 Diabetes, Recommended Dose (Week 26)

Pramlintide Facilitates Achievement of ADA Targets Type 2 Diabetes, Week 26

Weight Effect Type 2 Diabetes, Week 26

Pramlintide Therapy Offers Unique Metabolic Benefits in Type 2 Diabetes All Patients, Recommended Dose

Pramlintide Therapy

Number of Patients Included in Pramlintide Database

No Increase in Mortality Observed in Type 2 Diabetes Studies

Adverse Event Profile for Type 2 Diabetes Frequent TEAEs (% of Subjects), Overall Incidence > 5%, Excluding Hypoglycemia

Vision/Retinal Disorder Adverse Events

Serious Treatment-Emergent Adverse Events Were Similar (?1% of Subjects)

Severe Hypoglycemia (DCCT Definition) for Type 2 Diabetes Studies

Severe Hypoglycemia Event Rates Type 2 Diabetes All Pramlintide vs. All Placebo

Other Safety Observations Type 2 Diabetes

Pramlintide is Efficacious and Safe in Type 2 Diabetes

Pramlintide Therapy

Type 1 Diabetes Phase 3 Program

Summary of Pramlintide Effects Type 1, Recommended Dose

Pramlintide Phase 3 Studies Type 1 Diabetes HbA1c Effect for Total Population (ITT, 6 months)

Addition of Pramlintide to Insulin Reduces HbA1c in Type 1 Diabetes

Pramlintide Therapy Results in Greater Reduction in HbA1c Than Insulin Alone in Type 1 Diabetes, Recommended Doses (Week 26)

Pramlintide Facilitates Achievement of ADA Targets Type 1 Diabetes, Week 26

Weight Effect Type 1 Diabetes, Week 26

Pramlintide Therapy Offers Unique Metabolic Benefits in Type 1 Diabetes All Patients, Recommended Doses in Type 1

Pramlintide Benefits are Seen in Patients with Type 1 Diabetes Targeting Optimal Glycemic Control

Pramlintide Therapy

Number of Patients Included in Pramlintide Database

No Increase in Mortality Observed in Type 1 Diabetes Studies

Motor Vehicle Accidents/Injuries, All and Hypoglycemia-Related Type 1 Diabetes, Annual Event Rate per Patient-Year

Other Accidents/Injuries (Non-MVA), All and Hypoglycemia-Related Type 1 Diabetes, Annual Event Rate per Patient-Year

Adverse Event Profile for Type 1 Diabetes Frequent TEAEs (% of Subjects), Overall Incidence > 5%, Excluding Hypoglycemia

Most Nausea is Mild to Moderate Pramlintide-Treated Type 1 Patients in Long-Term Controlled Trials

Nausea is Dose Dependent Type 1 Diabetes Long-Term Controlled Studies

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Serious Treatment-Emergent Adverse Events (?1% of Subjects)

Assessment of Severe Hypoglycemia in Long-Term Controlled Trials

Severe Hypoglycemia Annual Event Rate Type 1 Diabetes

Severe Hypoglycemia Annual Event Rate Type 1 Diabetes Excluding Outlier

Severe Hypoglycemia Annual Event Rate over Time Type 1 Diabetes

Severe Hypoglycemia Annual Event Rate by Dose Type 1 Diabetes

Risk for Severe Hypoglycemia Decreases over Time Type 1 Diabetes, All Patients

Risk for Severe Hypoglycemia Decreases over Time Type 1 Diabetes, 30 µg QID

Pramlintide Alone Does Not Cause Hypoglycemia

Pramlintide Does Not Alter the Response to Hypoglycemia In Type 1 Diabetes

Risk of Hypoglycemia upon Initiation of Pramlintide Therapy in Type 1 Diabetes is Manageable

Pramlintide Benefits are Seen in Patients with Type 1 Diabetes Targeting Optimal Glycemic Control

Other Safety Observations Type 1 Diabetes

Pramlintide is Efficacious and Safe in Type 1 Diabetes

Guidelines for Initiation of Therapy

Guidelines for Chronic Therapy

Pramlintide as Adjunctive Therapy to Insulin

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Risk and Barriers to Current Insulin Therapy

Risk of Current Insulin Therapy

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Type 2 Diabetes — Adjunctive to Insulin Therapy

Pramlintide Overcomes Barriers and Challenges to Insulin Therapy in Type 2 Diabetes

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Pramlintide Overcomes Barriers and Challenges to Insulin Therapy in Type 1 Diabetes

Is the Reduction in HbA1c Obtained with Pramlintide Worthwhile?

Benefit of Pramlintide Therapy in Addition to Insulin

Benefits of Pramlintide Therapy in Addition to Insulin

Advantages of Addition of Pramlintide to Insulin Therapy

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Conclusion

Author: Amylin Pharmaceuticals