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Confidential, © Allergy Therapeutics Plc V1 November 2011

Allergy Vaccination

Dr Tom HoldichR&D Director

Allergy Therapeutics Plc, UK


Declaration of interest

I have the T-shirt (….well my wife‟s got it!)


Allergy

• An abnormal reaction of the immune system to a normal stimulus

• Pollen, animal dander, food, latex, nickel etc etc

• Mild local rash → fatal anaphylaxis

• Both genetic & environmental predisposing factors

• Atopic individuals – „the hygiene hypothesis‟

• Predominant Th2 type immune response

• The WHO classifies allergic disease as the fourth most important chronic disease in the world1

• Commonest allergy is allergic rhino-conjunctivitis (AR)

• Seasonal allergic rhino-conjunctivitis (SAR 43%) – „hay fever‟

• Pollens – grass, tree, ragweed

• Perennial allergic rhino-conjunctivitis (PAR 23%) – often associated with asthma

• House dust mite, animal dander1. Vervloet D.et al. Consensus et perspectives de l'immunothérapie spécifique dans les maladies allergiques. La Lettre (Supplément à la Revue Française

d'Allergologie et d'Immunologie Clinique) 1997; 37 (2): 4-5.


Symptoms of Allergic Rhino-conjunctivitis

Source: Burden of Illness Allergic Rhinitis in Canada, Keith, P.K. et al.Sponsored by ALTANA Pharma Inc, a Nycomed Co.


Patient Demographics1

• Approximately 20% of Canadians suffer from SAR3

• Substantial increases in the prevalence of AR in developed countries

in recent decades2-4

• Affects people between 18 – 50 years of age

• Equal among genders but may impact more women

• Develops before age 20 80% of the time

• Increased prevalence in:

• Higher socio-economic classes

• Polluted urban areas

• Individuals with family history

• Major incidence in Ontario & Quebec

BC:

11%

PR:

18%ON:

33%

PQ:

27% ATL:

11%

1. Source: Diagnosis & Management of Rhinitis (JAAIC 1998), p. 481.

2. US Dept of Health and Human Services. Evid Rep Technol Assess. 2002 May;(54):1-198. AHRQ

Pub No 02-E024.

3. Burden of Illness Allergic Rhinitis in Canada, Keith, P.K. et al.Poster, Sponsored by ALTANA

Pharma Inc, a Nycomed Co.


Burden of Disease

• Allergic rhino-conjunctivitis may not itself be serious but…..

• It can lead to asthma („allergic march) which can be serious

• It can be severely debilitating

• AR has a significant impact on quality of life:

• 43% of sufferers have trouble sleeping1

• 42% feel their are less productive at work2

• 65% say it disrupts their sporting activities3

• 51% of adults suffer from regular headaches4

• In the US, allergic rhino-conjunctivitis has been estimated to cause 100

million days of lost work, 28 million days of lost productivity, 16.7 million

physician office visits, 1.5 million missed school days and $5.9 billion in

direct expenditures each year.1. Demoly P. et al. Physician and patient survey of allergic rhinitis in France: perception of prevalence, severity of symptoms, care management and specific

immunotherapy. Allergy. 2008: 63: 1008–1014

2. Opinion Way – CFOA – Avril 2007

3. Opinion Way – CFOA – Juin 2008

4. CFOA Décembre 2009 - Enquête exclusive CSA / CFOA réalisée par téléphone le 30 septembre et le 1er octobre 2009


Treatment of AR

• Symptomatic1

• Antihistamines (eg Aerius, Allegra and Claritin)

• Oral or topical (nasal, ocular)

• Corticosteroids (eg Omnaris, Avamys, Beconase, Flonase, Nasacort, Nasonex, Rhinalar and Rhinocort)

• Usually topical (nasal), may be oral if severe

• Leukotriene receptor antagonists (eg Singulair)

• Advantages – widely available, relatively cheap

• Disadvantages

• 60% of AR sufferers do not have their symptoms controlled2

• Short term, doesn‟t treat cause

• Allergy Vaccination

(eg Pollinex-R, Center-Al, Suspal)

1. http://www.aaia.ca/en/allergic_rhinitis.htm

2. Burden of Illness Allergic Rhinitis in Canada, Keith, P.K. et al.Sponsored by ALTANA Pharma Inc, a Nycomed Co.


Allergy Vaccination(Allergen Immunotherapy/ Specific Immunotherapy (SIT))

• New treatment?

• 100 years of experience

• WHO position paper (1997)

• “Controlled studies have shown

that allergen immunotherapy is an

effective treatment for patients

with allergic rhinitis/ conjunctivitis,

allergic asthma….”

• “Immunotherapy is the only

treatment that may affect the

natural course of allergic diseases,

and it may also prevent the

development of asthma in patients

with allergic rhinitis”

Confidential, © Allergy Therapeutics Plc V1 November 2011 9

Allergy Vaccination - Background

• Allergy Vaccination may be

• Subcutaneous immunotherapy (SCIT) – allergy „shots‟

• Sublingual immunotherapy (SLIT) – oral liquid or dissolving tablet

• Most products are individual patient-specific (unlicensed)

• Practitioners in the United States currently use a wide variety of formulations, prepared for individual patients ad hoc from commercially-sourced allergen extract solutions

• Formulations are simple aqueous extracts without benefit of delivery technology

• In-office preparation may not performed under sterile conditions

• Allergen content is not standardized across patients

• No formal safety surveillance

• Conventional SIT uses a protocol of regular, slowly escalating dosages of allergen extract until a maintenance dose is reached. US treatment guidelines recommend:

• Starting dosing frequency is 1-3 times weekly up to maintenance dose (3-6 months), then reduced to every 2-4 weeks thereafter

• Total treatment time for optimal results is 3-5 years

• Overall perception – many injections, a bit dangerous?


Specific Immunotherapy – the modern age

• For common allergies – standardised, final form products

• Pharmaceutically manufactured (GMP) - „The Process is The Product‟

• Sophisticated formulations – modified allergens, depot mediators, adjuvants

• Standardised („Performance Validation‟ batches x3)

• Characteristics (MW profile, allergen „fingerprint‟, particle size, depot control)

• Potency (IgE, IgG, modification)

• Stability (expiry data, in-use, preservative)

• Comparability

• Preclinical data

• Immunogenicity; acute & chronic tox, genotox, reprotox, juvenile tox

• Standardised conditions of clinical use (labelled)

• Patient populations; diagnosis; contraindications precautions & warnings

• Dose regimen - Initial titration & maintenance courses – dose, frequency, duration –defined

• Actual clinical data

• Efficacy & safety data pertaining to labelled product use


Allergy Vaccination in Canada

„Final form‟ pharmaceutical vaccines currently licensed in Canada

Subcutaneous immunotherapy

CENTER-AL POLLINEX-R

Company Quorom & Western Allergy Services Nycomed

Indication Tree, Grass & Ragweed

Available in mixed or specific treatments

Ragweed only

Formulation Allergens on aluminum carrier Allergoids on tyrosine depot

Dose Schedule 9 injections 4 injections

Distribution Direct from manufacturers & wholesalers Direct from manufacturer & wholesalers

Availability Vials only Vials & PFS

Coverage Covered on most private plans &

reimbursed on ODB

Covered on most private plans &

reimbursed on ODB


Efficacy

SafetyConvenience

Registered

patented

products

Allergy Vaccine development targets

product differentiation in three areas

1. Glutaraldehyde

modified allergoid• Specifies the immune

response.

• Superior safety profile allows

administration of high allergoid

concentrations

2. Tyrosine adsorbate• Slow release formulation –

improved safety

• sustained immune stimulation

• synergistic with MPL

3. MPL® adjuvant• Immune stimulation

• restoration of TH1/TH2 balance

• probable T reg activity

Pollinex® Quattro

Just 4 injections, in only 3 weeks, efficacy already in 3 weeks

Confidential, © Allergy Therapeutics Plc V1 November 2011 13

Allergy Therapeutics R&D pipeline

• Four programs in clinical development for the leading

causes of seasonal allergic rhinitis (SAR)

• Development spend to date ~US$85m


Four clinical programs conducted involving ~

3000 patientsProgramme/ Study Purpose Location Subjects Status

Grass

Study 101 Residual allergenicity US 12 Complete

Study 201 Assay validation US 70 Complete

Study 202 Effects of MPL Canada 40 Complete

Study 203 Dose ranging Canada 74 Complete

Study 301 Phase 3 efficacy & safety Canada, US & Europe 1028 Complete

Tree

Study 101 Residual allergenicity Canada 12 Complete

Study 201 Assay validation US 70 Complete

Study 202 Effects of MPL Canada 40 Complete

Study 203 Dose ranging Canada 68 Complete

Study 204 EEC efficacy + Oak Canada 300 Clinical

Ragweed

Study 101 Residual allergenicity Canada 12 Complete

Study 203 Dose ranging US 68 Complete

Study 204 EEC efficacy ± MPL Canada 228 Complete

Study 205 1yr f/u EEC efficacy Canada 64 Complete

Study 301 Phase 3 efficacy & safety Canada & US 993 Complete

OralMPL Grass

Study 103 „Proof of Concept‟ Germany 80 Complete


‘Other products are also available’

• ALK/ Merck – Grazax – sublingual immunotherapy for grass pollen allergy

• Fast-dissolving tablet - kept under the tongue without swallowing for a

minimum of one minute

• Dosing: must start at least 4 months prior to the expected start of the grass

pollen season, must be taken daily for 3 years to be fully effective

• Ragweed tablet in development

• Stallergenes – Oralair – very similar to Grazax

• Circassia - ToleroMune cat, ragweed and grass products in development

• Short course format by intradermal injection

• Allergen fragments - T-cell epitopes


Allergy Therapeutics Company overview

16

• Allergy Therapeutics Plc is a fully integrated specialty pharmaceutical

company with a profitable core business (2010 revenues of US$67m) and

a patent-protected, late-stage development pipeline

• 1934 – C L Bencard Ltd allergen extracts for diagnosis &

immunotherapy

• 1949 – Acquired by the Beecham Group – Bencard Allergy Research

Department

• 1998 – Allergy Therapeutics Ltd separates from SmithKline Beecham

• 2004 – Allergy Therapeutics Plc listed on AIM of LSE

• Fully Integrated Specialty Pharmaceutical Company: Allergy

Vaccination: Research & Development, GMP manufacturing facilities,

sales & marketing infrastructure in Europe and Latin America,

distributor in Canada (Nycomed), looking for US partner

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