A world leader in allergy immunotherapy

Transcription

1 A world leader in allergy immunotherapy R&D and Business Briefing New York, May 2014

2 ALK s equity story An emerging speciality pharma with a global growth strategy Jens Bager President and CEO

3 Today s presenters Jens Bager President & CEO, ALK Prof. Moises Calderon Director of Clinical Trials Unit, Allergy and Clinical Immunology, Imperial College London Henrik Jacobi Executive Vice President, R&D, ALK José Moreno Toscano President, ALK Inc., (North America) Søren Niegel Executive Vice President, Commercial Operations, ALK Per Plotnikof Head of Investor Relations and Strategic Planning, ALK 3

4 Agenda 13.00: ALK An emerging speciality pharma company with a global growth strategy 13.30: Allergy Immunotherapy Treating the cause of allergic rhinitis and asthma 14.05: The US The next opportunity 14.55: Break 15.05: House Dust Mite tablets Treating the world s most prevalent allergy 16.05: Japan and the emerging markets Future growth opportunities 16.15: R&D with a commercial focus Globalising the tablet portfolio, expanding into asthma 16.20: Closing remarks and open Q&A Afterwards: Drinks reception 4

5 Forward-looking statements This presentation contains forward-looking statements, including forecasts of future revenue and operating profit as well as expected business-related events. Such statements are subject to risks and uncertainties as various factors, some of which are beyond ALK s control, may cause actual results and performance to differ materially from the forecasts made in this presentation. Without being exhaustive, such factors include general economic and business-related conditions including legal issues, uncertainty relating to demand, pricing, reimbursement rules, partners' plans and forecasts, fluctuations in exchange rates, reliance on suppliers, as well as market structure. An additional factor would be the consequences of potential side effects from the use of ALK's products, as allergy immunotherapy may be associated with allergic reactions of differing extent, duration and severity. 5

6 ALK at a glance Leading allergy immunotherapy (AIT) specialist AIT: Treats the root cause of allergy Products in all areas of AIT ALK has 33% of the global AIT market 1.5 million patients using ALK products 1,800 employees, ~350 in R&D SLIT-tablets: >10 years of R&D investment and clinical trials in ~ 15,000 patients Next R&D frontier: asthma treatment & prevention Sublingual tablets (SLIT-tablets) Sublingual drops (SLIT-drops) Subcutaneous (SCIT) or allergy shots Other, including diagnostics, adrenaline and anti-venom 6

7 A strong foundation for future growth Positive free cash flow expected in financial highlights Revenue: DKK 2.2bn (USD 400m) 13% SLITtablets 10% Other R&D expenses: DKK 416m (USD 76m) EBITDA (b.s.i.*): DKK 258m (USD 46m) CAPEX: DKK 209m (USD 38m) Equity ratio: 69% Dividend: DKK 5 per share (~USD 1) Shareholder info Listed on NASDAQ OMX Copenhagen Reuters: ALKB.CO / Bloomberg: ALKB.DC DKK million 3,000 2,500 2,000 1,500 1, % SCIT/SLIT-drops 25% 20% 15% 10% 5% Pct of revenue Market cap. ~USD 1.5bn Main shareholder: Lundbeck Foundation - 0% e** Revenue EBITDA b.s.i. (right) R&D expenses (right) 7 * Before special items **Before future income streams from product supply and sales royalties from SLIT-tablets in North America

8 Growth through global commercialisation Partnerships and collaborations to leverage growth ALK North America Own sales and distribution in the USA and Canada Merck partnership Exclusive rights to develop and commercialise SLIT-tablets in the USA, Canada and Mexico USD 290 million in milestones. Revenue from royalties and product supply North America 16% of revenue ALK Europe Own sales and distribution in 16 European countries Product Supply organisation with global capacity Europe 81% of revenue Torii partnership Exclusive rights to develop and commercialise SLIT-tablets in Japan EUR 60+ million in milestones. Revenue from royalties and product supply Eddingpharm collaboration Sales and distribution of marketed products in China Abbott collaboration Supply and marketing of SLIT-tablet portfolio in selected emerging markets International 3% of revenue 8

9 Europe: A market in transition ALK s core platform Total industry sales: ~USD 950m Europe: Market profile 1.3m patients on AIT 8% SLIT-tablets 92% SCIT/SLIT-drops Germany France 39% 31% 30% Others ALK 33% Mature, diverse markets Legacy and named patient products Restricted market access Uneven prescriber coverage Under regulatory transformation SLIT-tablets fully-documented and registered 31% Stallergenes 36% Others 9

10 Europe: Meeting the challenge of change Increased efficiency, focused investments and market shaping activities Europe: ALK s strategy Europe: Revenue Medium-term growth prognosis: 0-5% pa Activities to gain market share DKK bn USD m New product launches -1% +1% Improve earnings through cost efficiencies +4% Allergy Unlocked Raise awareness of disease burden Secure scientific support Improve market access Increase patient awareness Expand prescriber base Q

11 United States: The next opportunity High allergy prevalence, take-up of AIT affected by inconvenience USA: Market profile North America: Revenue Mainly allergy shots (SCIT) Mixing and compounding by allergists SCIT: High rejection and drop-out rate SLIT-tablets: First AITs approved by FDA (in 2014) DKK bn USD m % % % Q Merck partnership for SLIT-tablet portfolio Co-exists with ALK s allergen extracts business 11

12 Globalising a proven portfolio Expanding beyond established AIT markets International: Revenue DKK bn USD m % % -4% Existing markets Markets of specific interest: Argentina, Australia, Brazil, eastern Europe, Russia, South Korea and Turkey Q International markets: Torii partnership in Japan for HDM and Japanese cedar SLIT-tablets Eddingpharm in China: Sales and distribution of marketed products Abbott: Supply and marketing of SLIT-tablet portfolio in selected emerging markets 12

13 Agenda 13.00: ALK An emerging speciality pharma company with a global growth strategy 13.30: Allergy Immunotherapy Treating the cause of allergic rhinitis and asthma 14.05: The US The next opportunity 14.55: Break 15.05: House Dust Mite tablets Treating the world s most prevalent allergy 16.05: Japan and the emerging markets Future growth opportunities 16.15: R&D with a commercial focus Globalising the tablet portfolio, expanding into asthma 16.20: Closing remarks and open Q&A Afterwards: Drinks reception 13

14 Introduction to allergy and allergy immunotherapy Allergic disease, allergy vaccination and clinical evidence Henrik Jacobi Executive Vice President, Research & Development

15 Allergy: A chronic global disease million affected worldwide, 10-20% severely Respiratory allergies include allergic rhinoconjunctivitis (AR) and allergic asthma Allergic rhinoconjunctivitis is an important risk factor for the development of allergic asthma Key allergens Severe AR cases* North America Europe China Japan HDM, Grass, Ragweed, Tree 6-12m 11-22m 19-38m 5-10m 12m HDM, Grass, Tree HDM, Japanese cedar Treated with AIT* 3m 1.3m few few HDM 15 * Internal ALK estimates

16 What is allergy? An immunological overreaction against specific molecules in the environment of the patient Birch pollen 16 The specific molecules to which the patient reacts are called allergens Birch allergen: Bet v 1 molecule

17 What is allergy? Genes Environment Tolerance T cell Reaction Allergen IgE antibodies 17

18 What is allergy immunotherapy? Treatment with controlled doses of purified and standardised allergens Allergens are administered repeatedly in doses and at sites different from natural allergen exposure the immune response is changed Allergy immunotherapy Tolerance T cell Reaction Allergen 18

19 Allergy immunotherapy - mode of action appears to apply for all allergen species Immunotherapy (high dose Ag) IL 4 IL 13 B cell IgE Natural exposure (low dose Ag) + IgE APC Th2 Allergy ( ) ( ) IL 5 Th1 Treg Eosinophil IFN IL 10 TGF IgG IgG4 IgA 19 (Adapted from Robinson DS, Larche ML and Durham SR J Clin Invest 2004; 114: )

20 Allergy immunotherapy the essentials The only treatment documented to modify the underlying cause of allergic disease - through induction of immunological tolerance Effective treatment of symptoms Sustained effect after treatment has been completed The only treatment with potential for asthma prevention 20

21 PAT study with injection immunotherapy Reduced risk of developing asthma Subjects developing asthma (%) Subject developing asthma at 3, 5, and 10 years (percent of subjects; n=151) * * * OR=2.5 OR=3.1 OR=2.5 Control Alutard SQ * p< years 45% Treatment Follow-up Möller et al. JACI 2002;109: Jacobsen et al. Allergy 2007:62:

22 SLIT-tablet pipeline: Covering major allergies Clinical data from 36 trials in >15,000 patients Product GRAZAX Grass ARC GRAZAX Asthma prevention HDM SLIT-tablet HDM asthma HDM SLIT-tablet HDM rhinitis Tree SLIT-tablet Tree ARC GRASTEK * Grass ARC RAGWITEK TM * Ragweed ARC HDM SLIT-tablet* HDM rhinitis HDM SLIT-tablet** HDM rhinitis HDM SLIT-tablet** HDM asthma Japanese cedar SLIT-tablet Cedar tree ARC Pre-clinical Phase I Phase II Phase III Filing (exp.) Marketed TBC TBC TBC TBC TBC ARC: allergic rhinoconjunctivitis HDM: house dust mites *) Licensed to Merck for North America **) Licensed to Torii for Japan 22

23 Introduction to allergy and allergy immunotherapy AIT options, evidence and current treatment guidelines Professor Moisés A. Calderón MD PhD Director of Clinical Trials Unit Section of Allergy and Clinical Immunology Imperial College London

24 Allergen Immunotherapy Options, evidence and current treatment guidelines Professor Moisés A. Calderón MD PhD Section of Allergy and Clinical Immunology ALK R&D Business Briefing New York, May 21 st

25 Disclosures Lecture Fees ALK, Stallergenes, Merck, Allergopharma Industry-sponsored grant ALK, GSK Consultancy ALK, Stallergenes, Merck, Allergy Therapeutics, Hall Allergy Academia Chair of the Immunotherapy Interest Group, EAACI Special Committee on Immunotherapy, WAO Member of WHO-GARD programme 25

26 Allergen Immunotherapy SCIT First RCT SCIT SLIT First RCT SLIT WHO ARIA First Meta SLIT Large RCT SCIT First Meta SCIT Large RCT SLIT EBM Clinical Experience Clinical Evidence 26

27 Subcutaneous Immunotherapy Phase I : Up-dosing Weekly injections weeks Phase II : Maintenance Monthly injections 3-5 years minutes waiting period after each injection 27

28 Sublingual Immunotherapy Vials Pump Doseuse Disposable single dose Soluble tablets 28

29 SCIT and SLIT SCIT/SLIT SLIT/SCIT SCIT/SLIT SCIT/SLIT More than 50% of the current population of patients in Central Europe receiving allergen immunotherapy are on SLIT 29 Bousquet J and Demoly P. Allergy 2006; 61:

30 Adults Well-powered Big Randomized Placebo Controlled Trials in AIT Frew AJ et al. J Allergy Clin Immunol 2006; 117: n=410 SCIT Durham et al. J Allergy Clin Immunol. 2006;117: n=855 SLIT Dahl R et al. J Allergy Clin Immunol 2006; 118: n=407 SLIT Didier A et al. J Allergy Clin Immunol 2007; 120: n=628 SLIT Nelson HS et al. J Allergy Clin Immunol 2011; 127: n=439 SLIT DuBuske LM et al. Allergy Asthma Proc 2011; 32: n=1,028 SCIT Cox L et al. J Allergy Clin Immunol 2012; 130: n= 473 SLIT Nolte H. et al. J Allergy Clin Immunol 2012;129: AB143 n=784 SLIT Creticos P et al. J Allergy Clin Immunol 2012; 129: AB142 n=565 SLIT Children Röder E et al. J Allergy Clin Immunol 2007; 119: n=168 SLIT Bufe A et al. J Allergy Clin Immunol 2009; 123: n=253 SLIT Wahn U et al. J Allergy Clin Immunol 2009; 123: n=266 SLIT Blaiss M et al. J Allergy Clin Immunol 2011; 127: n=340 SLIT De Bot et al. Pediatr Allergy Immunol. 2012; 23: n=251 SLIT 30

31 SLIT Grass Allergen Tablet Maintenance of efficacy over 3 treatment years Improvement in combined symptom and medication score Grazax 75,000 SQ-T (TCS; adj means) Oralair 300-IR (AAdSS; adj means) 40% Reduction vs placebo (%) 34% 36% 34% End of treatment 27% 18% 32% 35% End of treatment 23% 2011 season 31 Durham et al. JACI 2010;125:131-8; Durham et al. Allergy 2010;65 (Suppl 92):Ab 1875 Didier A. CFA 2011; Stallergenes Symposium

32 Longer SLIT grass tablet pretreatment is associated with increased efficacy Significant clinical effect (p<0.05) when treatment is started approximately 8 weeks prior to the pollen season < 8 weeks 17% symptoms 23% medication > 8 weeks 37% symptoms 47% medication n=934 Reduction (%) Reduction in Medication Scores Reduction in Symptom Scores Projected Values Weeks prior to start of pollen season 32 Calderon MA et al. Allergy 2007; 62:

33 SLIT Safety SLIT has a very good safety profile for adults and children SLIT treatment is recommended to be taken at home Local reactions Bucco-lingual oedema, oral pruritus, throat irritation more frequent, mild to moderate in severity, generally did not require any treatment Systemic reactions very rare, mild-to-moderate severity There were no reported episodes of anaphylaxis, life-threatening reactions Radulovic S et al. Allergy 2011; 66: Lin S-Y. et al, JAMA 2013; 309(12):

34 Allergen Immunotherapy WHO position paper Effective in IgE-mediated disease with a limited spectrum (1 or 2) of allergies Effective in allergic rhinitis/conjunctivitis allergic asthma and systemic reactions to wasp/bee venom Should be combined with allergen avoidance, pharmacotherapy and patient education 34 Bousquet J et al. Allergy 1998; 53: 1-42

35 Recommendations for Management of Allergic Rhinitis: ARIA Guidelines Mild intermittent Moderate severe intermittent Mild persistent Intranasal steroid, LTRA s Moderate severe persistent Local cromone Second-generation non-sedating H 1 antihistamine Intranasal decongestant (<10 days) or oral decongestant Allergen and irritant avoidance (tobacco ++) Immunotherapy 35 Bousquet J et al. Allergy 2008:63: Suppl 86:1-160.

36 Asthma and Allergic Rhinitis are often co-morbid diseases Up to 40% patients with allergic rhinitis are reported to have concomitant asthma Up to 90% patients with asthma are reported to have concomitant allergic rhinitis 36

37 Management Approach Based on Control Children older than 5 years, adolescents and adults AIT should be considered only after strict environmental avoidance and pharmacological intervention Step 1 Step 2 Step 3 Step 4 Step 5 Asthma education Environmental control Reliever As needed inhaled SABA Select one Select one Add one or more Add one or both Low dose ICS Low dose ICS plus LABA Medium or high dose ICS plus LABA Oral corticosteroid (lowest dose) Controller options Leukotriene modifier Medium or high dose ICS Leukotriene modifier Anti IgE treatment Low dose ICS plus leukotriene modifier Sustained release theophylline Low dose ICS plus sustainedrelease theophylline 37 GINA global strategy for asthma management and prevention: updated

38 Allergen Immunotherapy for Respiratory Allergy AIT is an effective treatment in reducing symptoms and the need of rescue medication: Evidence based medicine. AIT provides a sustained effect after treatment has been completed. AIT has a documented immuno-regulatory effect of the underlying allergic disease. AIT is the only treatment with the potential for asthma prevention. 38

39 Questions & discussion Please raise your hand, then wait until a microphone reaches you 39 Company presentation : May 2014

40 Agenda 13.00: ALK An emerging speciality pharma company with a global growth strategy 13.30: Allergy Immunotherapy Treating the cause of allergic rhinitis and asthma 14.05: The US The next opportunity 14.55: Break 15.05: House Dust Mite tablets Treating the world s most prevalent allergy 16.05: Japan and the emerging markets Future growth opportunities 16.15: R&D with a commercial focus Globalising the tablet portfolio, expanding into asthma 16.20: Closing remarks and open Q&A Afterwards: Drinks reception 40

41 The US opportunity ALK s strategy and the partnership with Merck Jens Bager President and CEO

42 United States: Parallel growth strategy A strong partnership for SLIT-tablets, a growing allergen extracts business USA: ALK s strategy North America: Revenue Merck Partnership for grass, ragweed and HDM SLIT-tablets GRASTEK and RAGWITEK TM approved and launched in 2014, HDM tablet in Phase III DKK bn USD m % % % ALK North America Allergen extracts and other products delivered to allergists Q

43 Merck partnership for North America Co-exists with ALK s allergen extracts business Terms of the partnership Develop, register and commercialise SLITtablets in USA, Canada and Mexico Covers grass, ragweed and house dust mite Up to DKK 1.6 billion (USD 290 million) in milestone payments US$ 100 upfront and in milestones ~ US$ 85 million paid US$ 190 in sales milestones Revenue from royalties and product supply Partnership signed with Schering- Plough Schering- Plough acquired by Merck FDA establishes new efficacy requirements Merck submits BLAs for grass and ragweed SLIT-tablets GRASTEK and RAGWITEK TM approved and launched 43

44 The US opportunity Overview of the US market and ALK North America José Moreno Toscano President, ALK North America

45 United States: Market profile High allergy prevalence, low take-up of AIT due to inconvenience Billing: $2-3bn, Industry revenue: USD 120m 3m patients on AIT 0% SLIT-tablets 5% SLIT-drops 95% SCIT ALK 40% Greer 30% 30% Others USA: Market profile Dominated by SCIT, with self-mixing and compounding by allergy specialists 5,500 AIT practitioners; increasing interest from ENTs and others > 6 million severe patients eligible for AIT 45 Source: Internal market estimates

46 Allergen extracts: A commodity business AIT using extracts seen as a medical benefit with no approved products Market overview SCIT self mixing common among allergy specialists Increased off-label SLIT usage in recent years Diagnosis and other services important to physicians Reimbursed by private insurance, Medicare and Medicaid SCIT: self-mixing by allergists 46

47 Regulatory framework for allergen extracts The key ingredient in current AIT practice First classified by FDA in 1974 Last FDA classification project dates to allergens safe for diagnosis and treatment 134 food allergens safe for diagnosis 73 allergens safe for diagnosis Over 500 allergens for deletion Compounding and mixing practices under increasing FDA scrutiny 47

48 ALK footprint in North America 30 years in partnership with US and Canadian allergy specialists A recognised leader since 1984 North America: Revenue DKK bn USD m % +6% +8% Excluding SLIT-tablets Q Source materials, manufacturing and commercial capabilities One of only 4 companies with an FDA license to manufacture allergen extracts 250 employees in 5 locations, 25 reps >3,000 accounts across North America Allergenic extracts, diagnostic, treatments and services Key products: pollens, venom, mites, cat, mixes 48

49 United States: Parallel growth strategy SLIT-tablets to co-exists with allergen extracts business Business remains attractive For complex multi-allergic patients For allergies not covered by SLIT-tablets Continued service and support for allergists AIT expected to enjoy a higher profile: Increased documentation for SLIT-tablets More visible due to SLIT-tablet launches Potential expansion into adrenaline autoinjectors 49

50 The US opportunity Development and launch of GRASTEK and RAGWITEK TM Henrik Jacobi Executive Vice President, Research & Development

51 SLIT-tablets: The road to the US market US Phase III studies to support successful FDA approval Partnership signed with Schering- Plough Schering- Plough acquired by Merck FDA establishes new efficacy requirements Merck submits BLAs for grass and ragweed SLIT-tablets GRASTEK and RAGWITEK TM approved and launched GRASTEK GT-14 P05239 P05238 P08067 FDA AdCom FDA Approval HDM RAGWITEK TM P06081 P05233 P05234 P05751 P08067 FDA AdCom FDA Approval 51

52 GRASTEK : Approved in April 2014 GRASTEK For the treatment of grass pollen-induced allergic rhinitis with or without conjunctivitis confirmed by positive skin test or in vitro testing for pollen-specific IgE antibodies for Timothy grass or cross-reactive grass pollens Approved for use in persons 5 through 65 years of age Label One tablet daily to be placed under the tongue First dose should be administered in a healthcare setting with a physician experienced in allergic diseases Patients should be prescribed autoinjectable epinephrine and instructed in its use Initiate GRASTEK at least 12 weeks before the expected onset of each grass pollen season and continue treatment throughout the season For sustained effectiveness for one grass pollen season after cessation of treatment, GRASTEK may be taken daily for three consecutive years (including the intervals between the grass pollen seasons) 52

53 RAGWITEK TM : Approved in April 2014 RAGWITEK TM For the treatment of short ragweed polleninduced allergic rhinitis, with or without conjunctivitis, confirmed by positive skin test or in vitro testing for pollen-specific IgE antibodies for short ragweed pollen Approved for use in adults 18 through 65 years of age. Label One tablet daily to be placed under the tongue First dose should be administered in a healthcare setting with a physician experienced in allergic diseases. Patients should be prescribed autoinjectable epinephrine, and instructed in its use Initiate RAGWITEK at least 12 weeks before the expected onset of ragweed pollen season and continue throughout the season 53

54 The US opportunity The commercial potential of GRASTEK and RAGWITEK TM Søren Niegel Executive Vice President, Commercial Operations

55 Severe allergy: An area of unmet need Many patients reject or discontinue current treatment options An opportunity to change the statistics* <10% of diagnosed patients treated with AIT >6 million severe patients eligible for AIT SCIT: high rejection and drop-out rate 50% refuse treatment, 50% discontinue treatment within 1 year Major unmet need in treatment of AR, claiming: 3.5m lost work days 2m lost school days $14bn in direct costs SLIT-tablets are the first FDA-approved AIT treatments (approved in 2014) List price: USD 8.25 per tablet 55 *) Source: Merck s Briefing documents to the FDA. December 2013

56 Understanding the market Seasonal, dosing begins12 weeks before allergy season FEB MAR APR MAY JUN JUL AUG SEP OCT NOV DEC Dosing for GRASTEK Option for year round dosing Average grass pollen season Average ragweed pollen season Dosing for RAGWITEK TM 56

57 US: A new market for SLIT-tablets Difficult to draw conclusions from EU experience US vs European SLIT-tablet launches Vastly different healthcare environments Homogenous vs diverse Limited market access in Europe Merck 2014 has different launch capabilities to ALK 2007 Established respiratory franchise Experience of first-in-class launches SLIT-tablets at later stage of development Long-term and paediatric data >300,000 patients treated KOL adoption 57

58 Driving awareness Print coverage of GRASTEK and RAGWITEK FDA approvals Merck s Ragweed Pollen Allergy Drug gets U.S. Approval RAGWITEK Approved for Adult Ragweed Allergy Merck Bags FDA Approval for its Grass Pollen Pill GRASTEK FDA OKs RAGWITEK Hay Fever Tablet Teachable Moment for New Allergy Tabs FDA Clears Sublingual RAGWITEK for Ragweed Allergy Merck s GRASTEK Gets Larger Population, Easier Dosing Than Stallergene s Oralair Allergy Immunotherapy Without the Shots Got Hay Fever? New Tablets vs. Allergy Shots Allergy Shots in a Pill? FDA Approves Merck & Co s RAGWITEK Nothing to Sneeze at: Merck Hay Fever Drug Approved 58

59 Driving awareness Broadcast coverage of GRASTEK and RAGWITEK FDA approvals 59

60 Questions & discussion Please raise your hand, then wait until a microphone reaches you 60

61 Agenda 13.00: ALK An emerging speciality pharma company with a global growth strategy 13.30: Allergy Immunotherapy Treating the cause of allergic rhinitis and asthma 14.05: The US The next opportunity 14.55: Break 15.05: House Dust Mite tablets Treating the world s most prevalent allergy 16.05: Japan and the emerging markets Future growth opportunities 16.15: R&D with a commercial focus Globalising the tablet portfolio, expanding into asthma 16.20: Closing remarks and open Q&A Afterwards: Drinks reception 61

62 Tea/coffee break Please be back in your seats in 10 mins