1. 20 mars 2009 A renewal story

2. Safe Harbor This is an independent study performed by students from the Faculté des Sciences Pharmaceutiques de Lille The opinions expressed are our own and not necessarily those of Ipsen 2

3. Sales in comparison 3

4. A family business 4 French independent laboratory Owned by Beaufour family More than 20 products marketed in more than 100 countries Third Independent pharmaceutical firm in France Historical presence in primary care

5. Key figures: 2008 5 €971M Sales 4000 employees worldwide €203M cash generated 18.8% of sales allocated to R&D

6. PROFILE Primary care product: Gastroenterology Cardiovasular Cognitive disorders Specialized therapies : 3 areas Oncology Endocrinology Neuromuscular disorders CA 2008: 971,0 M€ (+5,5% vs 2007) 6

7. AN INTERNATIONAL COMPANY 7

8. Key figures 8

9. BACKGROUND 1929 : Dr Henri Beaufour « Beaufour laboratories » (Dreux) Romarène® (1929) Citrate de betaïne® (1954 ) 9

10. BACKGROUND 1970 : Expansion years « Beaufour-IPSEN » : Institut des Produits de Synthèse et d’Extraction Naturelle Willmar Schwabe Ginkor® (1972) Tanakan® (1975) Gingko Biloba 10

11. PRIMARY CARE 1972 Active substances Troxerutin A, heptaminol chlorhydrate, Ginkgo biloba extract Indications: Cardiovascular venous insufficiency of the lower limbs acute haemorrhoid episodes 11 GINKOR Fort®

12. PRIMARY CARE 1975 Active substance EGb 761® (Ginkgo biloba) Indications : Cognitive disorders Age-related cognitive disorders pathophysiological deficiency cochleovestibular disorders 12 TANAKAN®

13. PRIMARY CARE 1977 Active substance : Diosmectite (natural clay) Indications : Gastroenterology Chronic and acuate diarrhoea Pain associated with gastric and colonic disorders 13 SMECTA ®

14. PRIMARY CARE 1996 Active substance : Macrogol 4000, a linear polyethylene glycol polymer Indications : Gastroenterology Treatment of constipation for both adults and children 14 FORLAX®

15. A WILL TO GO FURTHER 15

16. GOING FURTHER Albert Beaufour : biotechnology research 1976 : Biomeasure Boston A. Beaufour research institute: Peptide- focused engineering Research relations with American universities 16

17. ONCOLOGY 1980 Partnership with Debiopharm® Active substance: Triptorelin : decapeptide, analogue of the natural hormone : GnRH Indications : Prostate cancer Uterin fibroids Endometriosis Early-onset puberty Female infertility 17 DECAPEPTYL®

18. NEUROMUSCULAR DISORDERS 1994 IPSEN bought Speywood (UK) Active substance: Botulinum neurotoxin type A complex (  acts at the level of the neuromuscular junction in the targeted muscle) Indications: Cervical dystonia Cerebral palsy in children Blepharospasm 18 DYSPORT®

19. ENDOCRINOLOGY 1995 Active substance: Lanreotide (somatostatin analogue -> octapeptide) Inhibits secretion and growth endocrine/paracrine/exocrine functions (growth hormone) Indications: Acromegaly Neuroendocrine tumours 19 SOMATULINE®

20. 1996 - 2002 IS IPSEN RESTING ON ITS LAURELS ? 20

21. R&D STRATEGY ? Dr Pierre BRAQUET R&D manager form 1982 – 1995 he participated to the discovery of the first antagonists of PAF from an extract of the Chinese tree Ginkgo biloba Directed research works related to somatulin  Since 1985, his researches got nowhere Atrial natriuretic factor Endothelin … 21

22. A FAMILY AFFAIR 1998 : Albert beaufour wants to stay independent. Buys his brother’s participations (50%) Alliance with CDC and Paribas AI Albert Beaufour  75,5% CDC and Paribas AI  24,5% 2000 : Albert entrusts his son-in-law, Stephane François, with the direction of the group 22

23. A FAMILY AFFAIR February 2000 : Albert Beaufour died (76 years old) His participation (75,5%) is shared among his 3 children November 2001 : Family conflict Stephane François is relieved from his duties 23

24. A FAMILY AFFAIR December 2001 J.L. Belingard 24

25. From Beaufour Ipsen to Ipsen 2003: The Group had its name changed from Beaufour Ipsen to Ipsen Renewed Executive Commitee 2001 2003 2007 19972007 20032008

26. A NEW TEAM A NEW STRATEGY 26

27. A NEW STRATEGY 27 Ipsen faces up to regulation Optimize its primary care portfolio Focus on targeted therapeutic areas Geographic expansion

28. STRATEGY HOW ? Product life cycle management Strong R&D Partnership policy Initial Public Offering 28

29. 29 PRODUCT LIFE CYCLE MANAGEMENT

30. 12% of sales 30 Tanakan® Many trials trying to prove efficacy HAS: insufficient SMR Price cut: -10% in july 2007 Threatened by disreimbursement GuidAge study: 8000 patients enrolled Currently underway prevention Alzheimer disease Life cycle management PRODUCT LIFE CYCLE MANAGMENT

31. Price cut: -15% in february 2006 Successive reimbursement rate cuts in France: CA 2005CA 2006CA 2007 61.2M€41.7M €36.9M € -11.5%-31.8% Marketing authorizations transferred to GTF (France, Monaco, Andorra) in august 2007 Ginkor Fort®

32. Other developments Adrovance®, from MSD Osteoporosis Comarketing along with MSD Adenuric®, from Teijin Chronic hyperuricemia in gout Ipsen obtained MA in Europe in may 2008 Exforge®, from Novartis ARA II + ICa 2+ BA058, from Ipsen PTHrP analog Licensed to Radius and Teijin 32

33. STRONG R&D 33

34. R&D original model « Discovery and Innovation » Dedicated to discover new chemical entities Targeted disease areas Out-licensing « Corporate Development » Bring a coherent portfolio of molecules to the market Both internal research and external business development In-licensing 34 2007: R&D division now organised around 2 entities:

35. R&D original model 4 R&D centres: PARIS Medicinal chemistry BOSTON Peptide engineering Protein engineering: improve the therapeutic BARCELONA: Advance drug delivery BATH: Steroid Engineering 35

36. R&D original model 36 Collaboration with academic research centres worldwide: Erasmus University Medical Center Rotterdam ERINE endocrinologye, diabete and metabolism Salk Institute proliferative and degenerative diseases

37. R&D original model clinical development pharmaceutical development business development regulatory affairs LONDON, PARIS, BOSTON: CLINICAL DEVELOPMENT AND REGISTRATION DREUX: PHARMACEUTICAL DEVELOPMENT BARCELONA: PHARMACOKINETICS 37

38. STRONG R&D 38

39. Focus on targeted therapeutic areas 39 Endocrinology Oncology Neuromuscular disorders

40. ENDOCRINOLOGY A major technological advance: first sustained-release formulation for injection without any excipient  6 months 1 injection per month (vs 2 or 3) Patent: direct holder of the patent expiration date: in 2015 in Europe and US (Somatuline® : 2005) 40 SOMATULINE AUTOGEL®

41. ENDOCRINOLOGY Product’s Life cycle Managment programmes: phase III: coadministration with pegvisomant acromegaly in Europe phase III: Asymptomatic neuroendocrine tumours in Europe Phase II: in Japan, partnership with Teijin acromegaly International expansion : FDA approval in 2007 for the treatment of acromegaly (=Somatuline Depot) Group’s competitor: Sandostatin® LAR® Depot (octreotide) Novartis painless and easy to use, gives it a competitive advantage 41 SOMATULINE AUTOGEL®

42. ENDOCRINOLOGY 42 SOMATULINE AUTOGEL® SomatulineSandostatin Indicationacromegaly NET acromegaly NET AdministrationSCIM Formulationready to usepowder to reconstitute Advantagepainless easy to use painful

43. ONCOLOGY Group’s competitors : Takeda/Pfizer-Wyeth/Abbott Enantone : worldwide leader, 6 months formulation expected in 2008 Astellas Eligard : 6 months formulation : 2007 in Germany, 2008 in France Sandoz/Hexal Leuprone (1 month) and Leupro (3 months) : 2007 in Germany 43 DECAPEPTYL ®

44. ONCOLOGY Life cycle management 3 phase III studies (International Breast Cancer Study Group) Combined hormonal therapy: breast cancer in premenopausal women  Decapeptyl®/ Aromasin® Pfizer a 6 month sustained release formulation: filed in 2008 Partnership with Debiopharm licence of know-how and marketing 44 DECAPEPTYL ®

45. STRONG R&D 45

46. Research programs New approaches in cancer treatment under hormonal control: Anticancer agents Angiomates multitarget antiproliferative anti-angiogenic acquisition (February 2004) BIM 46187 Cell signalisation: G-Protein signal CDC25 Phosphatase inhibitors regulation of cell cycle ONCOLOGY

47. Post-menopausal breast cancer expressing estrogenic receptors BN 83495 (STX 64) Phase I Treatment of side effects from LHRH-a based androgen-deprivation Acapodene® Phase III (2008) 47 Research programs ONCOLOGY

48. 48 Research programs ENDOCRINOLOGY Ghrelin agonist Regulating food intake and the gastro-intestinal function and treating cachexia 11ßHSD enzyme inhibitors Metabolic syndromes associated with obese patients with hyperinsulinemia Sustained-release growth hormone Long-term treatment of growth failure in children and growth hormone deficiency in adults

49. 49 Development programs ENDOCRINOLOGY Pituitary and neuroendocrine tumours Dopastatine : Second-generation somatostatin analogues and growth hormone antagonists Phase I Glycaemia control in diabetic patients BIM 51077 / R1583 Analogue of peptide hormone Glucagon Like Peptide-1 Phase II Sustained-release formulations Phase I (with Teijin) October 2003: exclusive licence to the rights to develop and market worldwide ( except Japan and France)

50. 50 Research programs HEMATOLOGY OBI-1 recombinant version of porcine factor VIII congenital or acquired haemophilia resistant to human factor VIII phase II trials in USA 17 July 2008 Ipsen completes purchase of all of OBI-1 assets from Octagen Corporation Emory University and

51. RESEARCH PROGRAMS 51

52. 52 Niche strategy Partnership policy

53. Niche strategy IPSEN does not keep marketing rights on molecules which will required too much promotion For example : In Diabetes In Osteoporosis

54. Niche strategy Antidiabetics : A large market: 24.1 Billion of Dollars 10.7 % Growth 2007

55. Niche strategy Ipsen licenses Taspoglutide Worldwide to Roche : exclusive worldwide rights to develop and market Taspoglutide Japan to Teijin : rights to develop and market Taspoglutide In France where Ipsen may elect to retain co-marketing rights. TASPOGLUTIDE

56. Niche strategy TASPOGLUTIDE Why ? Clinical trials limited Overall, 3884 patients were randomized for Januvia Only 1100 patients during 2 years No expertise in the domain A launch very expensive For exemple Januvia in France 27 million € promotion investment in 2008 14 million € of sales in 2008

57. Niche strategy BA058 Osteoporosis

58. Niche strategy BA058 BA058 is an analogue of PTHrP License to Radius in phase I Radius develop BA058 until phase II Radius License BA058 to Novartis start phase III

59. Niche strategy BA058 Why ? No expertise in the domain Clinical trials : More than 7000 patients during 5 years for Protelos An important marketing effort For example Actonel vs Pariet in France Actonel® ratio invests/sales : 0.28 Pariet® ratio invests/sales : 0.12 In osteoporosis the effort in near increase by 3 versus antiulcer

60. The University Emory Octagen Ipsen buy Octagen for 10,2 millions of dollars in July 2008 Licence with Ipsen in 1998 60 OBI-1 According to CDC (Centers for Disease Control), among 13000 peoples live with hemophilius A in United-state Niche strategy

61. Strategy France Different strategy in France because Ipsen have Sales force and a good corporate image in France Ipsen market and co-market product from other firm. For example : Adrovance, Nisis NisisCo … 61

62. PARTNERSHIP POLICY 62

63. PARTNERSHIP POLICY 2003  Marketing licence Nisis and Nisisco 2003  R&D 2003  Market Ipsen’s products in Japan 2004  R&D 2004  RetD 2004  Marketing licence Testim in France 2006  development and marketing licence BIM51077 2006  development and marketing licence Acapodène in UE 63

64. PARTNERSHIP POLICY 2006  R&D theranostic 2007 Erasmus medical center  R&D 2007  Toxine botulique 64

65. NICHE STRATEGY + PARTNERSHIP POLICY 65

66. Botulinum toxin : a high stake Growing market worth $1600M Allergan boasts 80% of the market with Botox®

67. Botulinum toxin: a high stake Ipsen has already a Botulinum toxin (Dysport®) Ipsen wants his piece of the cake Aesthetics is not part of Ipsen’s targeted therapeutic areas Ipsen is looking for partners specialized in dermatology…

68. Strategy botulic Toxin A IPSEN keeps right on therapeutics use But in aesthetic Medicis in USA Galderma in Europe and South-America Two specialists

69. Botulinum toxin: a high stake March 2006: agreement with Medicis (n°1 in dermic volume restoration) for North America Feb 2007: agreement with Galderma for Europe, Russia, then dec 2007: South America 69

70. Partnership with milestones: Potential of 193,6 millions de dollars with Medicis Already 90 millions of dollars have been paid Partnership with royalties: between 30 and 40% of sales 70 Botulinum toxin: a high stake

71. Aesthetic Market in United State is estimated to 300 – 400 millions of dollars In South America Galderma take 40 % of share market So If Medicis take 30 % of share market with 30 % of royalties Ipsen will earn 27 millions of dollars per year 71

72. Agreement with Medicis Limit of partnership policy July 2002: Development and distribution contract for Reloxin® between Ipsen and Inamed in USA Dec 2005: Allergan about to acquire Inamed Termination of the contract, Ipsen recovers its rights to Reloxin® for $10M Ipsen license rights to Medicis Waste of time

73. STOCKMARKET 73

74. Stockmarket An old idea 1998 Introduction was considered since 1998, year of the opening of the capital of the laboratory to the Caisse des Dépôts and Paribas Affaires Industrielles, which then took a participation of 20%. 2003 The conditions of market have not been favorable Wait until they improve 12/2005 Initial Public Offering

75. Stockmarket IPO 12/2005

76. Stockmarket Why ? To finance expansion by equity issue : 171 millions of euro Nearly one year of R&D for Ipsen ½ Tercica To pay back old shareholder : 151 millions of euro

77. Stockmarket Mayroy is the familial Holding Mayroy get more than 66.66% of the share So Ipsen has still a familial direction

78. Stockmarket Comparaison between Ipsen and other pharmaceutical firm : Sanofi-Aventis and Pfizer

79. Geographic Expansion 79 USA Japan

80. Conquering the USA 80

81. 1976: R&D Boston 2003: Inamed 2006: Medicis 2008: Tercica, Vernalis, Octagen (OBI-1)  Acquisitions are aimed at creating a sales force in USA Gaining a foothold in USA August 2008: Somatuline® approved by the FDA

82. Gaining a foothold in USA Ipsen needs sales-forces for Dysport and Somatuline Easier to buy firms than creating from nothing Endocrine-focused sales forceNeurology sales force Somatuline® Increlex® Dysport®

83. Conquering Japan 83

84. Japan conquest Agreement with Teijin, july 2003 Development and marketing of 4 Ipsen products in Japan GLP-1 analogue: diabetes type II PTHrP analogue: osteoporosis Somatostatine Autogel®: acromegaly Somatostatine SSTR-2 analogue: diabetic retinopathy Development and marketing of 1 Teijin product in Europe Xanthine Oxydase inhibitor (TMX-67): gout MA EMEA may 2008: Adenuric®

85. PARTNERSHIP POLICY  DRAWBACKS 85

86. Dependence on IP rights held by third parties Intellectual Property rights (patents, know- how and trademarks) held by third parties ProductPatent titularPatent expiration GinkorSchwabe2010 TanakanSchwabe2010 SmectaIPSENexpired Forlax-- DecapeptylDebiopharm2010 SomatulineTulane University2005 Somatuline autogelIPSEN2015 Dysport-- NeutropinaqGenentech2013 IncrelexGenentech2015

87. Financial During 3 years result increase faster than the turnover but with Tercica acquisition in 2008 it decrease. Consolidated profits 239 584 € Debt 171 090 € Net cash 66 224 €

88. Financial Expenditure in R&D are growth slowest than turnover but are still strong (182 millions of euro and 18,8% of turnover)

89. SWOT analysis 89 STRENGHTS Independent firm Technology platforms very developed Strong R&D capacities Product life cycle management Alliance capacity International marketing presence

90. SWOT analysis 90 STRENGHTSWEAKNESSES Independent firm Technology platforms very developed Strong R&D capacities Product life cycle management Alliance capacity International marketing presence Weak sales from primary care Few patents owned by IPSEN Dependent on 2 products (Tanakan, Decapeptyl) Dependent on partnerships

91. SWOT analysis 91 STRENGHTSWEAKNESSES Independent firm Technology platforms very developed Strong R&D capacities Product life cycle management Alliance capacity International marketing presence Weak sales from primary care Few patents owned by IPSEN Dependent on 2 products (Tanakan, Decapeptyl) Dependent on partnerships OPPORTUNITIES Aesthetic market : Botulinum toxin A US market Tanakan : Alzheimer prevention (?)

92. SWOT analysis 92 STRENGHTSWEAKNESSES Independent firm Technology platforms very developed Strong R&D capacities Product life cycle management Alliance capacity International marketing presence Weak sales from primary care Few patents owned by IPSEN Dependent on 2 products (Tanakan, Decapeptyl) Dependent on partnerships OPPORTUNITIESTHREATS Aesthetic market : Botulinum toxin A US market Tanakan : Alzheimer prevention (?) Generics and regulation  patents and prices Research process longer and more expensive Industry consolidation

93. CONCLUSION 93

94. Thank you for your attention 94 Specials thanks to Charlotte Marmousez