Crucell Combating infectious diseases. Annual General Meeting of Shareholders May 30 th, 2008

Transcription

1 Crucell Combating infectious diseases Annual General Meeting of Shareholders May 30 th, 2008

2 Agenda item 1 opening Mr. J.P. Oosterveld Chairman Supervisory Board 2

3 Disclaimer This presentation contains forward-looking statements that involve inherent risks and uncertainties. We have identified certain important factors that may cause actual results to differ materially from those contained in such forward-looking statements. For information relating to these factors please refer to our Form 20- F, as filed with the U.S. Securities and Exchange Commission on May 7, 2008, and in particular the section entitled Risk Factors. Crucell N.V. prepares it financial statements under International Financial Reporting Standards (IFRS). Deze presentatie bevat op de toekomst gerichte verklaringen, die inherente risico s en onzekerheden met zich brengen. Wij hebben bepaalde belangrijke factoren geïdentificeerd, die tot gevolg kunnen hebben dat huidige resultaten materieel afwijken van de resultaten die in dergelijke, op de toekomst gerichte verklaringen zijn opgenomen. Voor informatie met betrekking tot deze factoren verwijzen wij u graag naar onze Form 20-F, zoals ingediend bij de Amerikaanse Securities and Exchange Commission op 7 mei 2008, en in het bijzonder de paragraaf getiteld Risk Factors. Crucell N.V. stelt haar financiële verklaringen op volgens internationale financiële verslaggevings-richtlijnen (IFRS). 3

4 Agenda item 2 state of the business Ronald H.P. Brus Chief Executive Officer 4

5 Crucell overview Headquarters: Listing: Technology: Products: Facilities: Partners: Netherlands NYSE Euronext, NASDAQ, SWX PER.C6, AdVac, MAbstract, STAR, virosomes Vaccines and antibody products Switzerland, Korea, Spain, Sweden, Netherlands Global distribution; broad base of technology licensees Market Cap: Approx. 800 million (29 May 08) Holdings: 6.2% Galapagos Genomics N.V. (GLPG) 20% AdImmune Corporation (private) 5

6 Improving financials Total revenues and other operating income Loss for the period million million (22.8) (15.6) (45.9) % gross margins (2007) and improving (87.6) Net cash from operating activities Cash & cash equivalents at 31 December million 22.2 million (7.0) (15.0) 76.7 (54.0)

7 Solid growth total revenues and other operating income 2007 Product Sales ( 178 million) Pediatric 44% Respiratory/ Influenza 19% Travel 38% Other 10% Product Sales 178 million Service Fees 14 million License Rev. 12 million Grants 9 million million 213 Product Sales* 36 million Service Fees 2 million License Rev. 5 million Grants 5 million Q million Q4 141 Q3 Q2 Q * Q1 Product Sales: Paediatric 46%, Travel 38% and other products 16% Travel 27% million 7

8 Mission Combating infectious diseases 8

9 Highlights New contracts of $130 million awarded for Quinvaxem, bringing total up to $360 million Seasonal flu cell vaccine¹ planned submission in 2010 Rabies monoclonal antibody cocktail² enters Phase II in the US and the Philippines; fast track status Start of Rabies studies triggers first milestone payments; total milestones of 66.5 million in development period Solid growth of travel vaccines; Epaxal and Dukoral Highest CD8 immune responses ever in a TB vaccine study Record monoclonal antibody production yields on PER.C6 (15 g/l) Discovery human monoclonal antibodies for avian flu Key new license agreements signed Profitable vaccine development agreement³ Q108 total revenue and other operating income of 47.9 million, growth of 36% compared to same quarter of 2007 ( 35.2 million) Gross margin of 40% in the first quarter (23% in Q107) 1. developed by sanofi pasteur 2. partnered with sanofi pasteur 3. Wyeth pharmaceuticals 9

10 Crucell a global and fully integrated biopharma company 1. Vaccine business: stable and predictable sales & cash flow Largest independent vaccine player Vaccine sales in 60 countries 2. Multiple products in a broad pipeline; strong partnerships Vaccines Antibodies 3. Technology licensing: provides current income and future royalties PER.C6 AdVac MAbstract STAR Virosomes 10

11 Fully integrated business proprietary in-house know-how Vaccines Technology Research & Development Manufacturing Marketing & Sales Antibodies Leading technology PER.C6 AdVac MAbstract STAR Virosomes A broad clinical pipeline and development capabilities Five main manufacturing sites Global M&S reach: Building market position with trade products 11

12 Vaccine and antibody market growth accelerating Worldwide vaccine revenue (US$ billions) Worldwide antibody revenue (US$ billions) Vaccines Antibodies 25 16% % Source: RNCOS, Global Vaccine Market Outlook, November Source: Datamonitor, Monoclonal Antibodies Report June

13 Products and pipeline offering excellent scope for long-term growth Development stage Pre-clinic Phase I Phase II Phase III Marketed Comment Quinvaxem TM Hepavax-Gene MoRu-Viraten Fully liquid vaccine for protection against five childhood diseases Recombinant hepatitis B vaccine Vaccine for protection against measles and rubella (all age groups) Epaxal Junior Low dosage unique aluminum-free hepatitis A vaccine (0.25 ml) Epaxal Vivotif Dukoral Inflexal V Flavimun Unique aluminum-free hepatitis A vaccine Unique oral typhoid vaccine Internationally licensed oral vaccine against cholera (and ETEC) Virosomal adjuvanted influenza (all age groups) Yellow Fever vaccine; priority given to production MoRu-Viraten Influenza seasonal Developed by sanofi pasteur using PER.C6 ; planned submission in 2010 H9N2* Trial completed; findings expected first half 2008 Rabies antibody cocktail Fast Track Partnered with sanofi pasteur; Phase II studies started in US and Philippines Malaria Phase I trial in US on two sites; initial findings expected in 2008 Tuberculosis Ebola H7N1/Flupan* Partnered with Aeras; Phase I study show highest CD8 immune responses ever Partnered with VRC of NIAID; initial indication suggest safety & immunogenicity Developed by sanofi pasteur using PER.C6 HIV Partnered with Harvard; Phase I trial started in Q Factor V L/C H5N1 Avian antibodies* Blood coagulation Factor VL/C Results demonstrating potential pandemic preparedness * Pandemic influenza 13

14 Crucell a global and fully integrated biopharma company 1. Vaccine business: stable and predictable sales & cash flow Largest independent vaccine player Vaccine sales in 60 countries 2. Multiple products in a broad pipeline; strong partnerships Vaccines Antibodies 3. Technology licensing: provides current income and future royalties PER.C6 AdVac MAbstract STAR Virosomes 14

15 Main marketed vaccines offering excellent scope for growth Paediatric Travel & Endemic Respiratory Quinvaxem TM Pentavalent vaccine Epaxal Hepatitis A vaccine Epaxal Junior Hepatitis A vaccine Epaxal Junior Hepatitis A vaccine Inflexal V Influenza vaccine Hepavax-Gene Hepatitis B vaccine Vivotif Typhoid vaccine Third party distribution MoRu-Viraten Measles/Rubella vaccine Dukoral Cholera & ETEC vaccine Gardasil Recombinant HPV vaccine 15

16 Strategy marketed vaccines untapped source of growth Life-cycle management (prolong sales) Vaccines Untapped new markets (US) Focus on higher margins (segmentation) Quinvaxem Hepavax-Gene Inflexal V Epaxal Vivotif Dukoral MoRu-Viraten Pentavalent Hepatitis B Influenza Hepatitis A Typhoid fever Cholera & ETEC Measles/Rubella Focus on Sales & Marketing (increase penetration) 16

17 Growth of Quinvaxem fully liquid pentavalent, paediatric vaccine for endemic regions 17

18 Quinvaxem TM supranationals award new contracts to bring total to $360 million Quinvaxem TM vaccines sold Doses in million units 21.3 Fully liquid 5 in 1 vaccine: Diphtheria Tetanus Pertussis H. influenzae b Hepatitis B sales expected to be significantly above

19 Epaxal Junior hepatitis A vaccine; superior immunogenicity and local tolerability Launch in 2008 in South America and selected European countries 19

20 Dukoral the only oral cholera vaccine; significant untapped demand Dukoral market-penetration and growth all travelers seeking advice growth Sweden 37% 90% 15% Norway 24% 60% 24% Spain 3% 7% 55% Italy 3% 7% 13% Australia 2% 6% 50% Canada 6% 16% 50% Dukoral re-launch in the rest of continental Europe 20

21 Crucell a global and fully integrated biopharma company 1. Vaccine business: stable and predictable sales & cash flow Largest independent vaccine player Vaccine sales in 60 countries 2. Multiple products in a broad pipeline; strong partnerships Vaccines Antibodies 3. Technology licensing: provides current income and future royalties PER.C6 AdVac MAbstract STAR Virosomes 21

22 Pipeline offering excellent scope for long-term growth Development stage Pre-clinic Phase I Phase II Phase III Marketed Comment Quinvaxem TM Hepavax-Gene MoRu-Viraten Fully liquid vaccine for protection against five childhood diseases Recombinant hepatitis B vaccine Vaccine for protection against measles and rubella (all age groups) Epaxal Junior Low dosage unique aluminum-free hepatitis A vaccine (0.25 ml) Epaxal Vivotif Dukoral Inflexal V Flavimun Unique aluminum-free hepatitis A vaccine Unique oral typhoid vaccine Internationally licensed oral vaccine against cholera (and ETEC) Virosomal adjuvanted influenza (all age groups) Yellow Fever vaccine; priority given to production MoRu-Viraten Influenza seasonal Developed by sanofi pasteur using PER.C6 ; planned submission in 2010 H9N2* Trial completed; findings expected first half 2008 Rabies antibody cocktail Fast Track Partnered with sanofi pasteur; Phase II studies started in US and Philippines Malaria Phase I trial in US on two sites; initial findings expected in 2008 Tuberculosis Ebola H7N1/Flupan* Partnered with Aeras; Phase I study show highest CD8 immune responses ever Partnered with VRC of NIAID; initial indication suggest safety & immunogenicity Developed by sanofi pasteur using PER.C6 HIV Partnered with Harvard; Phase I trial started in Q Factor V L/C H5N1 Avian antibodies* Blood coagulation Factor VL/C Results demonstrating potential pandemic preparedness * Pandemic influenza 22

23 Pipeline highlights Tuberculosis Partnered with the Aeras Global TB Vaccine Foundation Encouraging preliminary results from the Phase I Ad35 tuberculosis vaccine study CD8 immune responses considerably higher than ever seen in a tuberculosis vaccine study Rabies antibody cocktail Partnered with sanofi pasteur Phase II clinical trial started in the United States Phase II clinical study started in the Philippines Start of Phase II studies triggers first milestone payments of a total of up to 66.5 million H5N1 Avian antibodies (pandemic influenza) Set of human monoclonal antibodies providing immediate protection and neutralizes the broadest range of H5N1 strains in preclinical testing Results demonstrating potential pandemic preparedness 23

24 Tuberculosis major causes of death worldwide, mainly children Tuberculosis estimated peak annual market prime-boost combination: US $1 Billion Partnered with the Aeras Global TB Vaccine Foundation Encouraging preliminary results from the Phase I Ad35 tuberculosis vaccine study CD8 immune responses considerably higher than ever seen in a tuberculosis vaccine study 24

25 Rabies virus transmitted from animals to humans causing a fatal disease 3 Infection of the brain Acute Rabies Death infection Virus transmission 2 Spread through nerves travelling to brain Rabies virus Maintenance of rabies virus in wild and domestic animals 1 Bite Local virus replication To date there are only six documented cases of human survival from clinical rabies 25

26 Estimated market opportunity peak annual sales exceeding $300 million India PEP need (dog bites) PEP Vaccine only PEP Vaccine + HRIG 17 million 3 million >0.1 million China 13 million 10 million >0.5 million Asia is a high volume market, currently HRIG supply constraint USA PEP need (treatments) PEP Vaccine + HRIG 45,000 45,000 USA is a high price / low volume market 26

27 Rabies antibody cocktail combined with vaccine; fully protects and shows neutralization Survival [%] Placebo Vaccine alone 20 IU/kg 20 IU/kg CL184 + vaccine HRIG + vaccine 0.5 IU/ml is the rabies virus neutralizing activity considered to be adequate by WHO The rabies antibody cocktail is safe and well tolerated 27

28 Antibodies avian H5N1 continues to spread around the world and changes continuously 28

29 Antibodies human mab CR6261 prevents death and blunts disease from H5N1 Infection H5N1 A/HK/97, 25 LD 50, i.n. CR6261 mab 15 mg/kg End days median clinical score survival [%] survival [%] death Severity of symptoms 0 CR6261 ctrl 0 CR6261 ctrl days after challenge 21 29

30 Human mab CR6261 prevents death and blunts disease even after four days Infection H5N1 A/HK/97, 25 LD 50, i.n. CR6261 mab 15 mg/kg End days median clinical score survival [%] death Severity of symptoms 0 CR6261 ctrl days after challenge 21 30

31 Antibodies human mab CR6261 deals with variability of other strains potent weak H5N1 (Clade 2.3) H5N1 (Clade 2.2) H5N1 (Clade 2.1) H5N1 (Clade 1) H5N1 (Clade 0) H1N1 H6N1 H9N2 Neg. Control >50 µg/ml NT 50 [µg/ml] Original figure from : Nature 444, November,

32 Antibodies human mab CR6261 prevents death by H1N1 before and after infection Infection A/WSN/33, 25 LD50 i.n. CR6261 mab 15 mg/kg End days survival [%] survival [%] CR6261 ctrl 0 CR6261 ctrl Crucell has an antibody that is broadly reactive and resistant to changes occurring in influenza virus 32

33 Crucell a global and fully integrated biopharma company 1. Vaccine business: stable and predictable sales & cash flow Largest independent vaccine player Vaccine sales in 60 countries 2. Multiple products in a broad pipeline; strong partnerships Vaccines Antibodies 3. Technology licensing: provides current income and future royalties PER.C6 AdVac MAbstract STAR Virosomes 33

34 Technologies PER.C6 : human designer cell line for the development and large-scale manufacturing of biopharma products AdVac : technology, used in combination with PER.C6, to develop recombinant vaccines MAbstract : applied for discovery of novel drug targets and identification of human antibodies STAR : designed to enhance production yields of recombinant human antibodies and proteins on mammalian cell lines Virosomes: a vehicle enabling the use of virus antigens in the making of vaccinations 34

35 The PER.C6 solution Know-how File Standard License Agreement Regulatory Support Working Cell Bank PER.C6 Licensee Vendor Network On Site Training Joint Program Set Up Continuous Support PERCIVIA The PER.C6 solution offers continuous technical support from the moment of a licensure agreement to the moment of regulatory support 35

36 PER.C6 based products in clinic Sponsors Products # Studies # Patients (incl. placebo) Countries AME/Eli Lilly, AERAS, Ark Therapeutics, Berlex/ Schering, Crucell, FLUPAN, Genvec, Merck & Co, ML Laboratories, NIH-VRC, NIH-NIAID, sanofi pasteur, Selective Genetics, Transgene Gene Therapy Vaccines mabs ~35* >5,000 * No PER.C6 -related AEs reported in any of the studies US, Canada, Belgium, Finland, France, Germany, Hungary, Norway, Sweden, Switzerland, UK, Malawi, South Africa, India, Thailand, Australia, Brazil, Peru, Puerto Rico, Dom. Rep, Haiti, Jamaica 36

37 Key licensing agreements Upfront payments Sanofi pasteur Vaccines Annual maintenance payments Milestone payments Influenza: cell culture vaccine (FluCell) PER.C6 cells in bioreactors of 20,000 liters Production agreement Lonza Planned submission in 2010 Upfront and milestones of 30 million Royalty payments as a % of net sales MedImmune (AstraZeneca) Antibodies Service fees years after launch Bacterial antibodies for treatment and prevention of hospital-acquired bacterial infection MAbstract technology programs Milestone payments may exceed US$ 40 million Undisclosed royalty on product sales 37

38 Key collaboration and commercialization partnerships Sanofi pasteur Rabies Monoclonal Antibody Cocktail Fast Track status by the FDA Phase I US & Indian studies completed Safe and well tolerated Phase II US started March 2008 Phase II Philippines started May 2008 Upfront payment of 10 million in December 2007; milestones up to 66.5 million Estimated peak annual sales exceeding $300 million Antibodies 38

39 Key development partnership Wyeth Pharmaceuticals Vaccines Crucell is responsible for the development and manufacture of certain components of the vaccine for use by Wyeth in clinical studies Development activities in Crucell's manufacturing facilities in Bern Wyeth is responsible for clinical development of the vaccine 39

40 Key profit sharing partnerships Novartis Quinvaxem TM : fully liquid 5 in 1 vaccine Vaccines Diphtheria Tetanus Pertussis H. influenzae b Hepatitis B 40

41 Healthy Ambition operational excellence: 15% cost savings* by the end of 2009 Growth of work-force, locations lead to complexity Crucell workforce (FTE year-end) Three potential drivers for operational excellence Create lean and flexible growth platform +280% 1,073 Synergy capturing Further integration to achieve synergies in costs and resources Crucell locations 2006 Cost reduction Create a competitive cost position despite increased complexity Growth funding Focus on lean operations to create cash generator for biotech pipeline * based on 2007 actuals, excluding R&D 41

42 Accelerating growth Secured new Quinvaxem contracts of $130 million, bringing total up to $360 million Strong vaccine sales; double digit growth going forward 2008: 20%* revenue growth Higher margins Positive cash flow Continue broadly licensing our technologies Pursue key partnerships Focus on progress in clinical development Full steam roll-out of operational excellence * Constant currencies = Weighted average EUR/USD rate of 1.38 in

43 Agenda item 2 financial review Leonard Kruimer Chief Financial Officer 43

44 Financial highlights 2007 Successful Quinvaxem launch drives strong autonomous growth More than 50% growth in revenue and other operating income; million compared to in 2006 Gross margin of 34% compared to 31% in 2006 Net loss of 45.9 million compared to 87.6 million in 2006 Cash and cash equivalents of million on December 31, 2007 Q108 Strong vaccine sales, higher license fees and other income Growth of 36% in revenue and other operating income; 47.9 million compared to 35.2 in the same quarter of 2007 Gross margin of 40% compared to 23% in Q107; better product mix and higher license revenues Net financial income & expenses negative 4.4 million in Q108; foreign exchange losses from weaker US Dollar and stronger Swiss Franc against Euro Net loss halved to 9.0 million; stronger sales and partial reversal of impairment ( 5.2 million) 44

45 Results million, except per share data Q Q FY 2007 FY 2006 Revenues and other operating income Gross margin (revenues) Percentage 40.1% 23.4% 33.8% 31.2% Operating expenses (26.0) (30.9) (129.8) (148.3) Loss for the period (9.0) (18.5) (45.9) (87.6) Loss per share (0.14) (0.29) (0.71) (1.53) 45

46 Revenues and other operating income million Q Q FY 2007 FY 2006 Revenues Product sales License revenues Service fees Other operating income Grants Other Total revenues and other operating income

47 Costs of goods sold million Cost of product sales* (124.6) (83.5) Cost of service fees (10.3) (7.0) (134.9) (90.5) * Includes purchase price adjustment of 18.3 million in 2007 versus 19.7 million in

48 Operating expenses million Research & Development Selling, General & Administrative Restructuring Impairment Total

49 Cash flow million Operating activities 22.2 (54.0) Investment activities (24.2) 22.1 Financing activities Exchange rate effect on cash (3.8) (0.8) Net increase cash Cash and cash equiv. December 31, Cash and cash equiv. March 31,

50 Outlook & Phasing 2008: 20%* revenue growth Higher margins Positive cash flow Revenues and operating income phased throughout 2008 like in 2007 Cash flow and working capital to significantly deteriorate in first half of 2008, normal due to seasonality of business Negative cash flow in first nine months to reverse in final quarter of 2008, ending the year with positive cash flow * Constant currencies = Weighted average EUR/USD rate of 1.38 in

51 Agenda item 3 a) proposal to maintain use of English language for Annual Accounts b) proposal to adopt Annual Accounts 2007 Mr. J.P. Oosterveld Chairman Supervisory Board 51

52 Agenda item 4 reservation and dividend policy 52

53 Agenda item 5 a) proposal to grant release from liability to Management Board b) proposal to grant release from liability to Supervisory Board 53

54 Agenda item 6 proposal to re-appointment Deloitte as external auditor 54

55 Agenda item 7 resignation of Mr. D. Koechlin as member of Supervisory Board 55

56 Agenda item 8 proposal to appoint Mr. S. Davis as member of Supervisory Board 56

57 Agenda item 9 a) proposal to re-appoint Mr. R. Brus as member of Board of Management b) proposal to re-appoint Mr. L. Kruimer as member of Board of Management c) proposal to re-appoint Mr. J. Goudsmit as member of Board of Management d) proposal to appoint Mr. C. de Jong as member of Board of Management 57

58 Agenda item 10 proposal to adopt remuneration of Supervisory Board 58

59 Agenda item 11 a) proposal to approve remuneration policy of Management Board b) proposal to approve additional ad-hoc option grant for Management Board 59

60 Introduction Revised short-term and long-term incentive plans (STI/LTI) In the course of 2007, the current policy and structure of the remuneration of the Board of Management was reviewed in light of: Governance regulations / developments Market developments Conclusion: no fundamental change of policy needed, only some adjustments Reasons for proposed change in structure in 2008: Decrease complexity Rebalance variable components to better reflect the responsibility of the Board of Management to achieve both short-term goals and long-term strategy 60

61 Re-balancing STI & LTI Current plan Revised plan STI - CEO: 75% of Annual Base Salary - Other Pos: 60% of Annual Base Salary - CEO: 65% of Annual Base Salary - Other Pos: 50% of Annual Base Salary LTI - CEO: 34% of Annual Base Salary - Other Pos: 26% of Annual Base Salary - CEO: 50% of Annual Base Salary - Other Pos: 40% of Annual Base Salary 61

62 Overview revised STI plan Results of review: Cash burn rate replaced by financial company milestones Shift from restricted stocks (or cash with a penalty of 25% reduction) to a pay-out in cash Pay-out curve starts at 70% achievement of milestones instead of the current 50% Maximum pay-out percentage according the current pay-out curve 100% - introduce notion of over-achievement by more performance driven pay-out zone to 130% 62

63 130% 125% 120% 115% 110% Pay-out curve STI Performance Incentive Zone 130% 125% 120% 115% 110% 105% 100% 95% 90% 85% 80% 75% 70% 65% 60% 55% 50% 45% 40% 35% 30% 25% 20% 15% 10% 5% 0% Existing Pay-out Curve Proposed Pay-out Curve Bonus pay-out as a % of target bonus 0% 5% 10% 15% 20% 25% 30% 35% 40% 45% 50% 55% 60% 65% 70% 75% 80% 85% 90% 95% 100% 105% Weighted average of achieved Milestones 63

64 Overview revised LTI plan Results of review: Decreased complexity of current LTI plan by removing the circuit breaker and TSR European Biotech peer group while maintaining the performance condition related to the NASDAQ biotech index Shift from shares to options Exercise period after cliff vesting equals 5 years (total option term of 8 years) Pay-out table related to NASDAQ biotech index remains the same 64

65 Proposed additional ad-hoc option grant Objective of additional option grant: Increase alignment shareholders and Management Board Provide an extra retention / motivational incentive Additional one-off option grant Vehicle # Options Performance conditions Pay-out Performance period Exercise period - Stock options - CEO: 300,000 - COO: 200,000 - Other pos: 150,000 - Absolute Total Shareholder Return of 50% measured 3 years after grant - 0% for below 50% TSR; 100% for 50% and above TSR -3 years -5 years 65

66 Agenda item 12 proposal to grant authority to Management Board to repurchase shares for period of 18 months 66

67 Agenda item 13 a) proposal to extent authorization period of Management Board to issue shares and grant rights to subscribe b) proposal to extent authorization period of Management Board to limit or exclude pre-emptive rights 67

68 Agenda item 14 proposal to amend articles of association in connection with modern electronic means of communication 68

69 Agenda item 15 questions 69

70 Agenda item 16 closing 70

71 Mission Combating infectious diseases Investor Relations: +31(0) or 71