MALARIA VACCINES DEVELOPMENT THE WAY AHEAD Joe Cohen

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 v Global vaccine supplier v 1. 6 billion doses of GSK vaccines distributed in over 168 countries v 90% of total volume went to the Developing World v Primary supplier to WHO, UNICEF, PAHO, GAVI APPMG BEAD meeting London, February 6, 2006

GSK Vaccine Programs addressing the needs of the Developing World v Combination vaccines facilitating delivery and compliance e. g. Tritanrix: D, T, Pw, Hep. B, Hib v Meningitis vaccines aimed at Africa’s “Meningitis belt” e. g. Men. ACW; Hib Men. AC v Rotarix early introduction in international markets based on medical needs v 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

Vaccine Research & Development Identify Produce Test in Proof of Antigens Animals 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 up to 10 -20 M$ 1 -10 yrs x x up to 50 -100 M$ -4 yrs BEAD meeting London, February 6, 2006 1 yr APPMG up to 500 -1 B$ x 2 -3 yrs 2

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

Pediatric CDP for RTS, S/AS 02 A up to Po. C In partnership with PATH-MVI 2001 2002 Gambia Ph I 6 -11 yrs Dose range 2003 2004 2005 Unblinding Ph I 1 -5 yrs Dose range ½ adult dose selected Ph I Safety 1 -4 yrs Mozambique Phase IIb Efficacy 1 -4 yrs with long term F/U APPMG BEAD meeting London, February 6, 2006

Summary of results from the Landmark Po. C Study in Mozambique* v Vaccine is safe and well tolerated in 1 -4 year old children v Efficacy against uncomplicated malaria: 35% v Efficacy against severe malaria disease: 50% v 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

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

The Way Forward: Clinical Development Plan v Establish Safety in infants – staggered with other EPI vaccines: 2005 -06 v Establish Safety and compatibility with current EPI vaccines and Po. C in infants – in co-administration with EPI vaccines: 2006 -07 v Multi-centric Phase III (Efficacy) in Africa (2008 -2009) v Process scale-up and build Industrial scale Manufacturing facility (2005 -2008) v 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 v Implementation of the Clinical Development Plan (GSK, PATH-MVI, Collaborators) v Production scaling-up and manufacturing facility built and validated (GSK) v Regulatory strategy developed (GSK, MVI-PATH, European Reg. Authorities, WHO, National Reg. authorities) v 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 v Create demand 9 9 v Advocacy Demand Forecasting Identify funding sources and mechanisms 9 GAVI, The Global Fund 9 Advance Purchase Commitments 9 9 9 v 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 v 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 v It will need to be integrated into existing public he APPMG BEAD meeting London, February 6, 2006

CONCLUSIONS – Main Messages v When the vaccine is available and registered, a rap APPMG BEAD meeting London, February 6, 2006

CONCLUSIONS – Main Messages v 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 v 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