APPMG BEAD meeting London, February 6, 2006 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 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  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 GSK Vaccine Programs addressing the needs of the Developing World

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

APPMG BEAD meeting London, February 6, Studies in The Gambia RecE.colibased strategies RTS,S studies inNon-immunes (US/EU) R16HBs RTS,S adjuvant studies Preclinical and CMI studies CS cloned, sequenced SKF/WRAIR CRDA Program Transferred toRixensart GSK/MVI Partnership 4 Program led by SKF/SBPhila Program led by SB/GSB BioRix Hashed =preclinical; Solid = clinical GSK publications ; Key POC studies in green A Brief History of the GSK Bio Malaria Vaccine Program 22 Studies in Mozambique 24

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

APPMG BEAD meeting London, February 6, 2006 Summary of results from the Landmark PoC 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: , 2004 * P. Alonso et al, Lancet, 366: , 2005

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

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

APPMG BEAD meeting London, February 6, 2006 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 Accelerate Introduction  Create demand  Advocacy  Demand Forecasting  Identify funding sources and mechanisms  GAVI, The Global Fund  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 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 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 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 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 CONCLUSIONS – Main Messages  GSK is committed to achieving this goal through strong Partnership with Governments, NGO, International and National Health authorities and donor organizations