ALK-Abelló Research & Development. Henrik Jacobi MD, EVP Research & Development

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1 ALK-Abelló Research & Development Henrik Jacobi MD, EVP Research & Development

2 Agenda Latest news on GRAZAX 3rd year data from long-term study (GT-08) Effect on asthma symptoms in children (GT-12) Status: Other tablet vaccines New product in pipeline The future of allergy vaccination Next generation of tablet vaccines March 6, 2008 R&D Presentation 2

3 Sustained clinical effect through 3 seasons (GT-08) 3rd GRAZAX treatment year: Clinical effect sustained Statistically highly significant results (p<0.001) Hay fever symptoms reduced by 37% Use of symptom-relieving medication reduced by 60% GRAZAX GT-08 study 1st season 2005 Median 2nd season 2006 Median 3rd season 2007 Median Symptom score reduced: Entire season 34% 44% 37% Medication score reduced: Entire season 53% 73% 60% March 6, 2008 R&D Presentation 3

4 Pollen seasons w. symptom scores Average daily rhinoconjunctivitis symptom score Pollen Pollen count count Symptom score, Placebo Symptom score, Grazax Days from defined grass pollen season start Pollen count (grains/m 3 ) March 6, 2008 R&D Presentation 4

5 Pollen seasons w. medication scores Average daily rhinoconjunctivitis medication score Pollen count Medication score, Placebo Medication score, Grazax Days from defined grass pollen season start Pollen counts (grains/m 3 ) March 6, 2008 R&D Presentation 5

6 Taking differences in pollen seasons into account Difference relative to placebo (Placebo-Grazax)/Placebo 50% 45% 40% 35% 30% 25% GRAZAX 2007 GRAZAX 2006 GRAZAX 2005 P-value P-value Number of days Length included of grass in defined pollen season grass pollen season March 6, 2008 R&D Presentation 6

7 Increased immunological effect through 3 seasons 0.6 Grass pollen specific IgG 4 in blood Δ Log 10 (IgG 4 ) (from initiation of treatment) Placebo Time from treatment initiation (months) 2005 season 2006 season 2007 season March 6, 2008 R&D Presentation 7

8 3rd year results from GRAZAX GT-08 study Sustained, highly significant clinical effect over 3 years Increased effect over 3 years when taking into account the differences between pollen seasons Increased immunological effect over 3 years Improved side effect profile over 3 years All findings support expectations of a sustained clinical effect after 3 years of continuous treatment March 6, 2008 R&D Presentation 8

9 GRAZAX in children (GT-12 study) Phase III clinical study with GRAZAX in children Application for registration to the European Health Authorities under submission Significant effect on rhinoconjunctivitis Corresponding to results from adults Symptom score reduced by 28% Medication score reduced by 65% Safety profile is confirmed Significant effect on asthma Asthma symptom score reduced by 64% March 6, 2008 R&D Presentation 9

10 Significant effect on asthma symptoms in children Significant effect on asthma Asthma symptom score reduced by 64% Average number of days with asthma symptoms in the pollen season reduced from nine (placebo) to three (GRAZAX ) Asthma will be an important future focus area Another important differentiator for ALK-Abelló s allergy vaccines Self-reported asthma symptoms Cough Wheeze Chest tightness / shortness of breath (dyspnoea) Exercise-induced symptoms March 6, 2008 R&D Presentation 10

11 GRAZAX clinical program Phase I safety Phase IV compliance Phase II dose finding Effect Phase I children Phase I safety Phase I children Phase II safety asthma Effect Phase III children Effect All efficacy studies: Efficacy demonstrated Phase I safety asthma Effect Effect Effect Phase III long-term effect European approval Phase III US Effect * * in relevant subset March 6, 2008 R&D Presentation 11

12 15 peer-reviewed scientific publications on GRAZAX Malling HJ, Lund L, Ipsen H, Poulsen L. Safety and immunological changes during sublingual immunotherapy with Standardized Quality grass allergen tablets. J Investig Allergol Clin Immunol 2006; 16 (3): Durham SR, Yang WH, Pedersen MR, et al. Sublingual immunotherapy with once-daily grass allergen tablets: a randomized controlled trial in seasonal allergic rhinoconjunctivitis. J Allergy Clin Immunol 2006; 117: Rak S, Yang WH, Pedersen MR, Durham SR. Once-daily sublingual allergen specific immunotherapy improves quality of life in patients with grass pollen induced allergic rhinoconjunctivitis: a double-blind, randomised study. Qual Life Res 2007; 16 (2): Kleine-Tebbe J, Ribel M, Herold DA. Safety of a SQ-standardised grass allergen tablet for sublingual immunotherapy: a randomized, placebo-controlled trial. Allergy 2006; 61: Calderon M, Essendrop M. Specific immunotherapy with high dose SQ standardised grass allergen tablets was safe and well tolerated. J Investig Allergol Clin Immunol 2006; 16 (6): Dahl R, Stender A, Rak S. Specific immunotherapy with SQ standardized grass allergen tablets in asthmatics with rhinoconjunctivitis. Allergy 2006; 61: Dahl R, Kapp A, Colombo G, et al. Efficacy and safety of sublingual immunotherapy with grass allergen tablets for seasonal allergic rhinoconjunctivitis. J Allergy Clin Immunol 2006; 118: Durham SR, Riis Grass allergen tablet immunotherapy relieves individual seasonal eye and nasal symptoms, including blocked nasal blockage. Short communication in Allergy 2007 Calderon et al. Prolonged pre-seasonal treatment phase with GRAZAX sublingual immunotherapy increases clinical efficacy. Short communication in Allergy 2007 Ibañez et al. Safety of Specific Sublingual Immunotherapy with SQ Standardised Grass Allergen Tablets in Children. PAI 2007 Bachert C et al., Cost-effectiveness of grass allergen tablet (GRAZAX(R)) for the prevention of seasonal grass pollen induced rhinoconjunctivitis - a Northern European perspective. Clinical and Experimental Allergy 2007; 37(5): Canonica G.W. et al., Cost-effectiveness of GRAZAX(R) for prevention of grass pollen induced rhinoconjunctivitis in Southern Europe. Respiratory Medicine 2007; 101(9), Bériot-Mathiot et al., Influence of time horizon and treatment patterns on cost-effectiveness measures: the case of allergen-specific immunotherapy with Grazax. Journal of Medical Economics, 2007; 10(3): Poulsen PB, Pedersen KM et al., [Economic evaluation of a tablet-based vaccination against hay fever in Denmark] (Danish), Ugeskrift for læger, 2008; 14;170(3): Dahl R, Kapp A, Colombo G, et al. Sublingual grass allergen tablet immunotherapy provides sustained clinical benefit with progressive immunological changes over 2 years. J Allergy Clin Immunol (In Press). March 6, 2008 R&D Presentation 12

13 GRAZAX clinical efficacy Percentage of patients feeling better / much better better or much better Percentage of patients feeling the same / worse / much worse First treatment season Percentage of patients with better or much better rhinoconjunctivitis symptoms in the first treatment season, compared with previous seasons A highly significant improvement of 49% over placebo March 6, 2008 R&D Presentation 13

14 Meet GRAZAX patient Tina Weikel, Sweden Play > March 6, 2008 R&D Presentation 14

15 Evolution of allergy vaccination Early research and inventions Pangramin SLIT launched GRAZAX launched Alutard SQ launched SLITone launched March 6, 2008 R&D Presentation 15

16 Different product characteristics Administration specialist injections Home tablet treatment Long-term efficacy Clinical documentation Established Ongoing clinical trial March 6, 2008 R&D Presentation 16

17 Similar clinical efficacy Number of patients Reduction in symptom score (median) Reduction in medication score (median) UK-22, one season % 54% GT-08, 1st season % 53% March 6, 2008 R&D Presentation 17

18 Preventive Allergy Treatment study (PAT) Sustained preventive effect after 10 years Control group Adapted from Jacobsen L. et al. Allergy 2007; 62: March 6, 2008 R&D Presentation 18

19 Other tablet vaccines in ALK-Abelló s pipeline Research Preclinical Phase I Phase II Phase III Marketed GRAZAX (grass) House dust mites Ragweed Tree (birch) Tablet program covers Three most prominent outdoor allergens in Europe and the USA (grass, tree and ragweed pollen) Most prominent indoor allergen in the world (house dust mite) March 6, 2008 R&D Presentation 19

20 Prevalence of allergic diseases Allergic patients of total population Grasses House Dust Mite Ragweed Birch Cat Weed Cedar, Japanese Dog Food Venom USA % of allergic population 65 million 56% 45% 49% 23% 39% n.a. 10% 19% 10% 13% Europe % of allergic population 87 million 52% 49% n.a. 14% 30% 27% n.a. n.a. 11% 13% Note: In average a patient is allergic to more than 2.3 sources. (Source: Arch Pediatr Adolesc med/vol 156, Oct. 2002) Sources: USA: Annals of Allergy, Asthma, & Immunology, Vol 81, September, 1998, Page 203 FF. Canada: Clinical and Experimental Allergy, 1997, Vol 27, Pages Europe: Europ J All Clin Immun, P 239 and Prel res, J All Clin Immun, V 106, Number 2, P 247 ff, Linneberg et al. Allergy to Cats (ALK-publication) page 2 based on 5 worldvide studies. Venom: Insect Sting Allergy, Ulrich R. Muller, Food Allergy: USA: Curr Opin Allergy Clin Immunol 2002 Jun; 2(3): Europe: Allerg Immunol (Paris 2002 Apr; 34(4): March 6, 2008 R&D Presentation 20

21 Introducing the cat allergy tablet Recombinant allergens Research activities have been initiated First clinical trials expected in 2010/11 Cat allergen Fel d1 March 6, 2008 R&D Presentation 21

22 Pioneering recombinant technology ALK-Abelló has over 20 years of experience in recombinant allergen technology ALK-Abelló were the first to characterize 3D structure of major allergens 3D allergen structure Bet v1, birch allergen Cover article in Journal of Immunology Industrial production processes Long-term stable supply of active ingredients Easy up-scaling Clinical profile Theoretically comparable to vaccines based on natural allergens March 6, 2008 R&D Presentation 22

23 The future strategy pioneering allergy vaccination since GRAZAX launched Focus on: Allergy treatment Immuno-modulation (changes in the immune system) Development of user-friendly alternatives Objective: To reach a much larger number of patients than those currently receiving injectionbased allergy vaccination March 6, 2008 R&D Presentation 23

24 Next generation tablets with adjuvants Allergy vaccines with improved clinical profile Faster onset of clinical efficacy Faster onset of long-term efficacy Further differentiation from symptomatic medicine Adjuvants Further stimulation of the immune system Increases the response to the vaccine Adjuvants in testing: Mineral salts Particulate delivery vehicles Microbial derivatives March 6, 2008 R&D Presentation 24

25 Number one in scientific impact ALK-Abelló 934 citations Number of citations per year Ref.: ISI Web of Science, Feb Stallergènes 261 citations Allergopharma 255 citations Exclusive IP rights securing freedom to operate 97 patent families covering areas such as recombinant allergens, mutated allergens, expression systems & tablet technologies March 6, 2008 R&D Presentation 25

26 Questions? March 6, 2008 R&D Presentation 26