MALARIA VACCINES DEVELOPMENT: THE WAY AHEAD

1. MALARIA VACCINES DEVELOPMENT: THE WAY AHEAD Joe Cohen, Ph.D. Vice President R&D Vaccines for Emerging Diseases & HIV APPMG BEAD meeting London, February 6, 2006

2. GSK: A global Vaccine Company • Global vaccine supplier • 1.6 billion doses of GSK vaccines distributed in over 168 countries • 90% of total volume went to the Developing World • Primary supplier to WHO, UNICEF, PAHO, GAVI APPMG BEAD meeting London, February 6, 2006

3. GSK Vaccine Programs addressing the needs of the Developing World • Combination vaccines facilitating delivery and compliance e.g. Tritanrix: D, T, Pw, HepB, Hib • Meningitis vaccines aimed at Africa’s “Meningitis belt” e.g. MenACW; Hib MenAC • Rotarix early introduction in international markets based on medical needs • R&D on new vaccines for which primary or exclusive need is in DCs, e.g. Malaria, TB, HIV APPMG BEAD meeting London, February 6, 2006

4. Vaccine Research & Development Identify Antigens Produce Antigens Test in Animals Proof of Concept Phase I II III File Registration/Post marktng Research (inc. Immunology) Preclinical Development (inc. Formulation Science) Clinical Development (inc Post Marketing Surveillance Transfer Process to Manufacturing Build Facility x x up to 10-20M$ up to 50-100M$ up to 500-1B$ x x x 1-10 yrs 2-3yrs 2-4 yrs  1 yr APPMG BEAD meeting London, February 6, 2006

5. Program Transferred to Rixensart 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 00 01 02 03 04 Program led by SKF/SB Phila Program led by SB/GSB Bio Rix 24 16 Hashed = preclinical ; Solid = clinical GSK publications ; Key POC studies in green A Brief History of the GSK Bio Malaria Vaccine Program CS cloned, SKF/WRAIR GSK/MVI CRDA sequenced Partnership Preclinical and CMI studies RTS,S adjuvant studies 1 2 4 17 Rec E. coli based strategies 3 6 8 10 R16HBs RTS,S studies in Non-immunes (US/EU) 11 12 13 15 18 19 5 7 9 Studies in The Gambia 14 20 21 22 Studies in Mozambique 23 APPMG BEAD meeting London, February 6, 2006

6. Pediatric CDP for RTS,S/AS02A up to PoCIn partnership with PATH-MVI 2005 2001 2003 2004 2002 Unblinding Gambia Ph I 6-11 yrs Dose range Ph I 1-5 yrs Dose range Mozambique ½ adult dose selected Ph I Safety 1-4 yrs Phase IIb Efficacy 1-4 yrs with long term F/U APPMG BEAD meeting London, February 6, 2006

7. Summary of results from the LandmarkPoC Study in Mozambique* • Vaccine is safe and well tolerated in 1-4 year old children • Efficacy against uncomplicated malaria: 35% • Efficacy against severe malaria disease: 50% • Protection persists for at least 18 months * P. Alonso et al, Lancet, 364:1411-20 , 2004 * P. Alonso et al, Lancet,366:2012-18, 2005 APPMG BEAD meeting London, February 6, 2006

8. Significance of the results • Represent a major scientific breakthrough • Estimated vaccine efficacy is comparable to that of existing or contemplated malaria preventive methods (eg. insecticide impregnated bed nets, indoor spraying, IPTi) • If efficacy confirmed in subsequent clinical evaluation • This vaccine will have a significant public health impact APPMG BEAD meeting London, February 6, 2006

9. The Way Forward: Clinical Development Plan • Establish Safety in infants • staggered with other EPI vaccines: 2005-06 • Establish Safety and compatibility with current EPI vaccines and PoC in infants • in co-administration with EPI vaccines: 2006-07 • Multi-centric Phase III (Efficacy) in Africa (2008-2009) • Process scale-up and build Industrial scale Manufacturing facility (2005-2008) • File submission: 2010 APPMG BEAD meeting London, February 6, 2006

10. WHAT NEEDS TO BE DONE OVERTHE NEXT 4 YEARS IN ORDER TO AVOID ANY DELAYS IN VACCINE DEPLOYEMENT APPMG BEAD meeting London, February 6, 2006

11. Prepare for introduction • Implementation of the Clinical Development Plan (GSK, PATH-MVI, Collaborators) • Production scaling-up and manufacturing facility built and validated (GSK) • Regulatory strategy developed (GSK, MVI-PATH, European Reg. Authorities, WHO, National Reg. authorities) • Implementation strategy: integration with EPI and with other malaria control measures [GSK and partners, International Health Authorities (WHO, UNICEF) and National Heath Authorities] APPMG BEAD meeting London, February 6, 2006

12. Accelerate Introduction • Create demand • Advocacy • Demand Forecasting • Identify funding sources and mechanisms • GAVI, The GlobalFund • Advance Purchase Commitments • Important at beginning of Phase III clinical development • Financial under pinning for decisions on manufacturing facilities • Guaranteed number of doses to be purchased • Coordinated strategy between public and private sector APPMG BEAD meeting London, February 6, 2006

13. CONCLUSIONS – Main Messages • An effective vaccine against malaria will become a reality in the short to mid-term future and possibly as early as 2010/2011 APPMG BEAD meeting London, February 6, 2006

14. CONCLUSIONS – Main Messages • It will need to be integrated into existing public health interventions (EPI vaccination, Malaria prevention measure) in endemic regions APPMG BEAD meeting London, February 6, 2006

15. CONCLUSIONS – Main Messages • When the vaccine is available and registered, a rapid and broad introduction must be our common goal APPMG BEAD meeting London, February 6, 2006

16. CONCLUSIONS – Main Messages • Now is the time to start planning for • Manufacturing • Regulatory Strategy • Implementation policy • Accelerated introduction • Vaccine procurement mechanisms APPMG BEAD meeting London, February 6, 2006

17. CONCLUSIONS – Main Messages • GSK is committed to achieving this goal through strong Partnership with Governments, NGO, International and National Health authorities and donor organizations APPMG BEAD meeting London, February 6, 2006