World Federation of Hemophilia Global Forum

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Recombinant Porcine Factor VIII a promising
treatment for patients with inhibitors to Factor
VIII (congenital and acquired hemophilia A)

• World Federation of Hemophilia Global Forum
• 24-25 September 2009
• Innovations and Updates

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DISCLAIMER

• This presentation includes only summary
  information and does not purport to be
  comprehensive. Forward-looking statements or
  target dates contained herein are for
  illustrative purposes only and are based on
  managements current views and assumptions. Such
  statements involve known and unknown risks and
  uncertainties that may cause events to differ
  materially from those anticipated in the summary
  information.
• The Company expressly disclaims any obligation or
  undertaking to update or revise any
  forward-looking statements or target dates
  contained in this presentation to reflect any
  change in events, conditions, assumptions or
  circumstances on which any such statements are
  based unless so required by applicable law.
• All product names listed in this document are
  either licensed to the Ipsen Group or are
  registered trademarks of the Ipsen Group or its
  partners.

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An innovation-driven, International, Specialty
Pharma Group

• Four targeted areas
• Oncology, Endocrinology, Neurology, Hematology
• 4 approved specialty therapies in the US
  (Apokyn, Dysport, Somatuline Depot and
  Increlex)

Strategic focus on specialist care

• Focus on hormone-dependent diseases, peptide and
  protein engineering and innovative delivery
  systems
• RD expense of 20 of sales
• 4 centers in Boston, Paris, London and Barcelona

Differentiating RD capability

• Biotechnology production platform and product
  development expertise
• A fully-fledged peptide manufacturing capability
• Two manufacturing facilities FDA-audited,
  approved for US products

An integrated player
Ipsen wishes to partner with the medical
community patient associations To develop a
new, innovative hematology treatment
worldwide For the benefit of patients with
inhibitors to Factor VIII
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Clinical Background

• Congenital hemophilia A with inhibitors to hFVIII
  
• The development of neutralizing antibodies
  (inhibitors) to human FVIII following replacement
  therapy is a major complication in hemophilia A
• Patients no longer respond to hFVIII therapy
• Inhibitors develop in about 28 of severe
  hemophilia A patients
• Additionally, 3 to 13 of mild and moderate
  hemophilia A patients also develop inhibitors
• Acquired factor VIII inhibitor (Acquired
  hemophilia)
• Rare affects 1 to 2 individuals in 1,000,000
  and occurs predominantly in older individuals
• A small proportion of younger patients may
  develop the disease, predominantly postpartum
  women
• Clinical manifestation is more severe and
  anatomically diverse than in congenital
  hemophilia A
• Mortality rate 20 bleeding often spontaneous
  or in response to minimal trauma

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OBI-1s mode of action is maintenance of
intrinsic pathway activity due to its anticipated
low cross reactivity with circulating inhibitors
FXII
FXIIa
FXI
FXIa
FVII
Ca
Extrinsic pathway
FIX
Intrinsic pathway

FVIII
TF
FVIIIa
FIXa
or
FVIIa TF
B
T
Ca
FX
FV
T
FVa
FXa
Ca
PT
T
FG
Fibrin Clot
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OBI-1 is a recombinant protein formulated without
animal-derived products

• 94 homologous with human fVIII
• B-domain deleted
• Amino acid linker combining A2 and A3
• Baby hamster kidney cells
• Two viral reduction/inactivation steps
• Lyophilized in vials containing 500 IU OBI-1
• Coagulant function equivalent to human fVIII

Courtesy of Ipsen Hematology PMT
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OBI-1 Clinical Experience Phase II - Study
OBI-1-201

• Study design
• A prospective, open-label, non comparative study
  to assess the hemostatic activity of OBI-1 in
  congenital hemophilia A patients with inhibitors
  and non-life or -limb threatening bleeding
  episodes
• Dosing
• Loading dose given in patients with measurable
  anti OBI-1 antibody titers only.
• The initial treatment dose was 50 U/kg and was
  given 5 minutes after the loading dose
• Subsequent doses of OBI-1, if necessary, were as
  follows 50, 50, 100, 100, 100, 150, 150 U/kg
  given 6 hours apart
• Efficacy
• 9 subjects had 25 bleeding episodes treated with
  OBI-1 (5 patients with gt1 bleed)
• All bleeds (25/25) were successfully controlled
  with 8 or less injections of OBI-1 (median total
  dose 224 U/kg)
• 20 of the 25 bleeds (80) were controlled with 1
  treatment dose plus the loading dose when
  applicable (median total dose of 201 U/kg)
• In subjects with repeated exposure to OBI-1 and
  who had an increase in titer there was no
  increase in the number of injections required to
  control a bleeding episode

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OBI-1 Clinical Experience Phase II - Study
OBI-1-201

• Safety and Immunogenicity
• A total of 41 OBI-1 injections were administered
  in 9 subjects
• Individual dose ranging from 50 U/kg to 576 U/kg
• One subject had a treatment-emergent adverse
  event considered possibly related to the study
  drug
• Infusion reaction rated as mild and controlled
  with diphenhydramine
• When retreated for a subsequent bleed the subject
  did not reported any AE
• Eight out of nine (89) subjects developed
  anti-pFVIII antibodies following exposure to
  OBI-1 and in subjects receiving repeated OBI-1
  treatment higher anti-pFVIII titers did not
  affect efficacy nor safety
• No increase in incidence of AEs with increased
  doses
• No increase in number of injections of OBI-1
  required with increased titer

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OBI-1 phase III clinical plan first prospective
clinical trials in acquired hemophilia and severe
bleeds in congenital hemophilia A with inhibitors
Study 302 in patients with congenital hemophilia
A and inhibitors to hFVIII Treatment of life-
or limb threatening bleeding and other serious
hemorrhage
Study 301 in patients with acquired factor VIII
inhibitor (acquired hemophilia) Treatment of all
acute serious bleeding episodes
Both will be of similar design Open label,
non-comparative prospective studies, about 40
patients in each study
Based on input received from regulatory agencies
to date Ipsen is on schedule for Phase 3
activities by Q1 2010
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• Feel free to contact us
• Jeffry Lawrence Senior Director Medical
  Development - Hematology
• jeffry.lawrence_at_ipsen.com 1 508 478 0144
  Boston area, MA
• IPSEN, 27 Maple Street, Milford MA 01757, USA
• THANK YOU!