Therapeutic Vaccines

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• Therapeutic Vaccines Diagnostics for
• Autoimmune and Allergic Diseases

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ApitopesTM.

• Patented, platform technology to select
  ApitopesTM
• (Antigen Processing Independent epiTOPE)
• Highly specific therapeutic peptide vaccines
• Induce cells to selectively suppress excessive
  immune responses
• Naturally reset the balance of the immune system
• Prevent treat life threatening autoimmune
  allergy diseases
• Large potential markets with high unmet needs
• Experienced management
• Therapeutic vaccine for multiple sclerosis in
  Phase IIa

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Clinical Context

• Abnormal immune response can cause life
  threatening conditions e.g. MS, RA, transplant
  rejection, allergy
• Current therapies treat symptoms or suppress
  immune system
• increased infections
• increased risk of cancer
• Ideal therapeutic regime would re-instate normal
  immune balance and avoid global immune
  suppression
• This is our approach to allergy autoimmune
  disorders treatment using therapeutic vaccines
  and is proven

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ApitopeTM Peptide Vaccine Identification Platform

• Define protein antigen responsible for disease
• Identify epitopes (peptides) in protein using
  ApitopeTM know-how
• Select apitopesTM using patented high throughput
  methodology
• Test in transgenic pre-clinical models in vivo
• Test on human samples in vitro
• Product Candidates for pre-clinical development

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Mechanism of Action - Natural Process
Soluble peptide epitopes e.g. ATX-MS-1467
Soluble epitope does not trigger inflammation (No
danger signal)
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ATX-MS-1467 Key Features

• Synthetic soluble copies of peptide fragments
  (epitopes) from human Myelin Basic Protein
• High specificity
• lt 0.000 06 of CD4 Tcells will respond to
  ATX-MS-1467
• No widespread stimulation of T cells will occur
• Immune response to infection and cancer not
  affected
• Efficacy in MS models immune system both in
  vivo in vitro
• Safe well tolerated in preclinical safety and
  toxicity tests
• MHRA approved first in man Phase Ib/IIa clinical
  trial in MS patients commenced March 2007 66
  enrolment achieved already

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Modified Disease Progression in MS Model
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Reduced Side Effects Improved Efficacy
Disease Specificity
Increasing Side Effect Frequency
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ATX-MS-6 Induced Tolerance to MBP but not
PPDHuman T-Cell Receptor Transgenic Mouse
Results
Stimulation index proliferation of antigen
stimulated cells divided by proliferation of
cells cultured in medium alone Draining lymph
node cells were cultured for 3 days prior to
labeling with 3H-thymidine Draining lymph node
cells were re-stimulated with myelin peptide or
PPD in vitro
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Expertise - Unmet Need - Market Opportunity

• Multiple Sclerosis
• 700,000 sufferers in EU and USA
• High economic burden
• High prices tolerated
• Diagnostics
• current methods take 4 to 6 years
• no blood test for MS currently available
• Prevention of Factor VIII Inhibition
• 12,000 Haemophilia A sufferers in USA
• 20 to 30 of patients develop inhibitors of
  Factor VIII
• Factor VIII sales expected exceeded 600 m in 2005

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Continued Progress to Key Value Points
Q3 2009
2009
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Intellectual Property

• Peptide Selection Method
• International publication number WO 02/16410 A2
• Publication date 28th February 2002
• Method for selecting apitopes that induce
  tolerance CoM
• Expected WW notice of allowance - 12 months
• Tolerogenic Peptides from Myelin Basic Protein
• Intl. Application No. PCT/GB03/00399
• Filed 30/01/2003 with a priority date of
  01/02/2002
• Granted in US January 2006
• Expected RoW notice of allowance - 12 months
• Further applications filed for diagnostics
• Apitope owns all IP derived from collaboration
  with Baxter

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ApitopesTM Reduced Side Effects Improved
Efficacy
Disease Specificity
Increasing Side Effect Frequency