1. 1 AMYLIN ACCADEBLED Sophie – DAUSQUE Guy – VLEMINCKX Camille Février 2008

2. 2 Company Overview Amylin Pharmaceuticals, Inc. 9360 Towne Centre Drive San Diego California 92121 Amylin Europe Ltd. Mendelstraße 11 D-48149 Münster Germany Locations and Subsidiaries

3. 3 Total employees : 1900 R&D investment +++ Focus on new peptide hormone candidates Two marketed products (first-in-class medicines) BYETTA ® and SYMLIN ®  Diabetes Create a sustainable growth for Amylin Company Overview Business Description

4. 4 Company Overview Biopharmaceutical company Biotech, Drug Discovery Discovery Development Commercialization CARDIOVASCULAR DISEASE OBESITY DIABETES

5. 5 Amylin: The Second  -Cell Hormone -First reported in 1987 - 37-amino acid neuroendocrine hormone -Important regulator of glucose influx into bloodstream -Co-located and co-secreted with insulin from pancreatic  -cells -Equivalently deficient in type 1 and type 2 diabetes as insulin Amylin Insulin Unger. Williams Textbook of Endocrinology. 1992. The beginning …

6. 6 Interest in Neurohormones GIP LEPTIN Regulation of (1) Energy homeostasis (2) Fat metabolism (3) Glc metabolism (4) Body weight AMYLIN Regulation of (1) Appetite (2) Food intake (3) Postprandial [glucose] GLP-1 (1) Induces Glc-dep insulin secretion (2) Inhibites Glc-dep glucagon secretion (3) ↓ food intake and body weight (4) Stimulates β cell proliferation GIP (1) Induces Glc-dep insulin secretion (2) Stimulates β cell proliferation PYY (1)Induces satiety 6

7. 7 Amylin discovered by researchers at Oxford University  Foundation of the company Pramlintide (  SYMLIN®) Amylin analog Exenatide (  BYETTA®) GLP-1 mimetic  Licensed from researcher John Eng Continuous-infusion version of GLP-1  Acquired rights from Restoragen Inc. Chemical Ligation technology  Acquired rights from Gryphon Leptin  Licensed from Amgen GIP Receptor agonists  Licensed from Diabetica 1987 1995 1996 2002 2005 2006 Feb 2006 March

8. 8Pipeline 8

9. 9 DIABETES

10. 10 Diabetes market Medical treatment based on the level of Hemoglobin A1C → < 7% : no medical treatment → 7-9% : oral diabetes agents → > 9% : insulin 15M diagnosed in US Incidence +++ 90-95% are type 2 10

11. 11 Traditional consensus Discrimination in the 2 nd and 3 rd line based on : –Efficacity : glucose level –Safety : hypoglycemia risk –Others benefits : Cardiovascular Modalities of use Weight loss Cost

12. 12 Source : Non-insulin therapies for type 2 diabetes, mona Ashiya and Richard E.T. Smith, News and Analysis, volume 6, October 2007, Nature Publishing group SALES PRESCRIPTIONS

13. 13 MARKETED PRODUCTS BYETTA ® ExenatideBYETTA ® Exenatide SYMLIN ® PramlintideSYMLIN ® Pramlintide

14. 14 GLP-1=glucagon-like peptide-1; GIP=glucose-dependent insulinotropic polypeptide Section12, 12.2Section12, 12.2 Release of active incretins GLP-1 and GIP  Blood glucose in fasting and postprandial states Ingestion of food  Glucagon (GLP-1)  Hepatic glucose production GI tract DPP-4 enzyme Inactive GLP-1  Insulin (GLP-1and GIP) Glucose- dependent Glucose dependent Pancreas Inactive GIP Beta cells Alpha cells  Glucose uptake by peripheral tissue Exenatide ® MECHANISM BYETTA ® Incretin mimetic 14

15. 15 Ingestion of food  GLUCAGON GI tract Pancreas Pramlintide MECHANISM of SYMLIN ® Amylin analog INSULIN AMYLIN Stomach Blood sugar TISSUE 15

16. 16 Adjunctive therapy Type II Diabetes (for patients who have inadequate control despite treatment with oral agents Metformine+ SFUand/or TZD) Adjunctive therapy to mealtime Insulin Type I and II Diabetes (for patient who have failed to achieve desired Glc control despite optimal insulin therapy) Approval clinical indications None but Symlin has completed phase II studies for weight loss Unapproved/ Off-label uses NoneDrugs in the same class Anti-diabetic, Incretin mimeticAnti-diabetic, Amylin analogTherapeutic class June 2005 (USA) April 2007 (Europe) June 2005 (USA)Market availablity April 28, 2005March 17, 2005FDA approval date Amylin/Eli LillyAmylin PharmaceuticalsManufacturer BYETTA / BYETTA / exenatide SYMLIN / SYMLIN / pramlintideBrand name / Generic name None

17. 17  Provides a bridge to insulin therapy  Induces weight loss  For diabetics the most difficult to treat  Requires extra injection in addition to Insulin Market Niche $201,94$99,40 - $397,60 Cost for 30 day supply Nausea, vomiting, diarrhea, jitteriness, dizziness, headache Pancreatitis Nausea, vomiting, abdominal pain, headache, fatigue and dizziness Most common side Effects 5 µg - 10 µg twice daily prior to meals 15 µg - 120 µg prior to major meals Depending : (1) Type I or II (2) response to therapy Dosage / Administration

18. 18 BYETTA ® Net product sales Europe : Agreement with EliLilly - Global development and commercialization of Byetta - Launched in 30 countries during 2007 USA : Effective execution in the market place - High adoption by the diabetes specialists > 85% - Growth in use among Primary Care Physicians (PCPs) > 700 000 patients since its introduction Positive results (3 pivotal studies) FDA accepted for review FDA Approval NDA Room T° usage Submitted NDA Launch in Europe EU Approval Late 2003June 2004Sept 2004April 2005Nov 2006Feb 2007April 2007 M$

19. 19 SYMLIN ® Net product sales Strategy > 80 000 patients Approvable letter !Additionnal trials! 2 nd A. letter !Additionnal data! Submit response FDA Approval Consultation FDA  Clinical trials NDA Sympen Oct 2001Dec 2001Dec 2003Sept 2004March 2005Oct 2007 M$

20. 20 Type II Diabetes Market 20

21. 21 EXENATIDE LAR Collaboration pipeline

22. 22 Exenatide LAR Project First once-weekly injection for type 2 diabetes  52 doses a year vs. 730 or greater Based on Alkermes’ proprietary technology for long-acting medications Better efficacy and tolerability than BYETTA -Gradual, controlled release (24 hours a day and 7 days a week) -Consistent concentration of exenatide provided Improves Anticipates Patient compliance and outcomes

23. 23 Exenatide LAR Phase II Study Maggs D, et al. Presented at EASD Annual Meeting, Copenhagen-Malmö, Denmark-Sweden, September 14–17, 2006. HbA1C Change (%)Weight Loss (kg) Placebo LAR Exenatide LAR 0,8 mg Exenatide LAR 2 mg

24. 24 Exenatide LAR Comparator Trial 30-week, open-label, noninferiority study Type 2 diabetes : 295 subjects Open-ended extension ongoing Results A1C reduction from baseline of ~1.9% compared to ~1.5% Average weight reduction of ~8 pounds in both groups No major or severe hypoglycemia Improved tolerability ~30% less nausea

25. 25 Exenatide LAR Submission Timing FUTURE STUDIES 3 superiority trials underway to support commercialization -Once-weekly vs. TZD vs. DPP-4  Added to metformin background therapy -Once-weekly vs. insulin glargine  Added to background Met+SU therapy - Monotherapy study vs. Metformin

26. 26 Exenatide LAR Type II Diabetes Market

27. 27 OBESITY The increasing burden of obesity OBESITY DIABETES

28. 28 Obesity Market Sibutramine Xenical $ 426 m $ 723 m $ 1.366 m Acomplia (antagonist CB1)

29. 29 PIPELINE PRODUCTS In-house pipeline

30. 30 PROTAGONISTS INTO Program Integrated Neurohormonal Therapy for Obesity Program Key role of neurohormones in regulating appetite and energy balance  Studies of the interaction among these hormones within the brain  Uncover their full therapeutic potential Amylin  Pramlintide or Amylinomimetics PYY 3-36 Leptin  Metreleptin

31. 31 Pramlintide + Leptin Pramlintide + Leptin Proof of concept (synergy) – Phase II 24-week Clinical Obestity study : Phase IIA, randomized, double-blind, active-drug-controlled, multicenter study 177 overweight and obese patients (BMI 27-35 and weight average ~205 pounds) 31

32. 32 Lost average : 25 pounds continuous weight loss till the end 12,7% (p<0,001) Pramlintide + Metreleptin Lost average : 17 pounds weight loss leveled off toward the end 8,4% of weight loss Pramlintide No report of weight loss Metreleptin (r-metHuLeptin) Most common side effects : (1) injection site adverse events (2) nausea - mild to moderate and transient nature Pramlintide + Leptin Pramlintide + Leptin Study results

33. 33 SWOT ANALYSIS

34. 34 THREATS OPPORTUNITIES WEAKNESSES STRENGHTS Byetta New management team Strategic alliances

35. 35 Agreement for the global developement and commercialization of exenatide Byetta + Byetta LAR Alliance Eli Lilly / Amylin Advantages :  International  Commercial Operating profits In US shared equally between Amylin and Lilly Outside US 80% Lilly / 20% Amylin  Royalties Developement and Commercialization cost In US shared equally between Amylin and Lilly Outside US 100 % Lilly

36. 36 Alliance Alkermes / Amylin ALKERMES = Biotechnology company Targets : CNS disorders, addiction and diabetes Extended-release injectable, pulmonary, and oral products Two commercial products : - Risperdal consta® (Risperidone LAR) First and only atypical antipsychotic medication LAR (Janssen-Cilag) - Vivitrol® (Naltrexone) Once-mounthly injectable medication  treatment of alcohol dependence (Cephalon) Medisorb injectable sustained release drug delivery technology Developement and manufacturing of exenatide LAR 36

37. 37 THREATS OPPORTUNITIES WEAKNESSES Narrow customer concentration Narrow Market difficult to extend Pancreatitis risk Reliance on third party manufacturers STRENGHTS Byetta New management team Strategic alliances

38. 38 Reliance on third party manufacturers BYETTA ® Reliance on Bachem and Mallinckrodt  To manufacture its long-term commercial supply of bulk exenatide Reliance on single-source manufacturers  For some of the raw materials used by Bachem and Mallinckrodt Reliance on Wockhard and Baxer  Manufacture the dosage form of Byetta in cartbridges NO MANUFACTURING CAPABILITIES SYMLIN ® Bachem and Lonza  commercial supply of bulk pramlintide acetate Baxter  dosage form of Symlin in vials Wockhardt  dosage form of Symlin in cartridges Ypsomed  components for the Symlin disposable pen Hollister-Stier  assembly of the pen

39. 39 THREATS OPPORTUNITIES Exenatide LAR INTO Obesity program Symlin indication expansion Manufacturing facilities TZD decline WEAKNESSES Narrow customer concentration Narrow Market difficult to extend Pancreatitis risk Reliance on third party manufacturers STRENGHTS Byetta New management team Strategic alliances

40. 40 THREATS Regulations Industry consolidation Competition OPPORTUNITIES Exenatide LAR INTO Obesity program Symlin indication expansion Manufacturing facilities TZD decline WEAKNESSES Narrow customer concentration Narrow Market difficult to extend Pancreatitis risk Reliance on third party manufacturers STRENGHTS Byetta New management team Strategic alliances

41. 41 Competition DIABETES AND METABOLIC DISORDERS AstraZeneca Bristol-Myers Squibb GlaxoSmithKline Lilly Merck Novartis Novo Nordisk Pfizer Sanofi-Aventis Takeda Pharmaceuticals OBESITY : Few products… Sanofi-Aventis : Acomplia Roche : Xenical Abbott : Meridia … But a lot of failures!!!

42. 42 COMPANY FINANCIAL

43. 43 Financial statements Sources of revenues : –Products: Byetta : direct / indirect Symlin : Direct, only in the US –Collaborative agreement : Eli Lilly ( sept 2002)

44. 44 Financial statements

45. 45 Financial statements

46. 46 Forecast Consensus

47. 47 Forecast Consensus could be modified by recent results : – The FDA approved its pen device for delivering its diabetes drug SYMLIN, but rejected its application to increase SYMLIN's label to include patients using basal insulin. → no label expansion → impact on amylin’s plans to develop the active ingredient in Symlin as weight-loss drug : program INTO –Deception by the results of a 30-week comparator study of once- weekly exenatide long-acting release (LAR) injection and BYETTA® (exenatide) injection taken twice daily in patients with type 2 diabetes → positive results but not sufficient

48. 48 Consequences on the market 48

49. 49Conclusion Sources of revenues threatened –Small markets for the two products –No label expansion in a near period –Growth of number of competitor on the byetta’s market Sources of depenses in growth –Early-stage and late-stage programs (proof of efficacy and safety, launch of exenatide LAR) –Construction of manufacturing facility for exenatide LAR Weak pipeline –Few products –Strong links between the products

50. 50 Conclusion « The Amylin story is tied to the success or failure of his potential blockbuster Exenatide LAR »

51. 51 Thank you for your attention Questions ?