GSKs Commitment to Malaria Didier Lapierre Vice President

GSK’s Commitment to Malaria Didier Lapierre Vice President, Head of Global Clinical Development Centre for Early Development and DDW Vaccines All Party Parliamentary Malaria Group Meeting 8 July 2008

A Global Company Committed to the Diseases of the Developing World GSK is the only company with drugs and vaccines in development for the Big Three killer diseases: AIDS, TB and malaria In 2007 we provided 85 millions epivir-combivir tablets and our licencees 183 millions tablets More than 3 million doses of GSK Bio’s vaccines are distributed every day to 169 countries Close to 80% of vaccine doses go to the developing world Ranked #1 on the first ever Access To Medicines Index(2008)

GSK’s Has a Comprehensive Approach to Malaria Prevention Treatment Advocacy and mobilising support Vaccine Development Drug Development Philanthropy and Community Engagement

GSK DDW Drug Discovery Centre Tres Cantos 122 Scientists with expertise in Drug Discovery Partly supported by MMV, TB Alliance and DNDi Supported by world-wide GSK R&D ID CEDD Management Team and scientists MDR, Preclinical and clinical development GSK Site services 8, 500 m 2 of research facilities, including two P 3 facilities, for in vitro (220 m 2) and in vivo (4, 000 m 2) experimental work

GSK DDW Drug Discovery Pipeline Portfolio in 2008 DHODH Inh. A Malate Falcipain synthase MGI Pyridone BU Isoquine GSK 369796 sitamaquine P III Pentostam Halfan GSK antimicro Pleuros Macrolides Pyridone GW 932121 tafenoquine P III Zentel Malarone Target to Lead to Candidate to Po. C Tres Cantos Tuberculosis Malaria Other DDW Neglected Diseases Post-Po. C and Launched

GSK-DDW Drug Discovery Partnerships Major Partnerships Targets and projects Tools and Know-How

African Malaria Partnership Three projects to address education and behavioural change in African communities “Credit with Education” - Freedom from Hunger Teaching village women about malaria prevention and treatment in 6 countries in West Africa “Ugandan Malaria Partnership” – AMREF Training community health workers to deliver home based Malaria treatment to children and pregnant women “Malaria prevention and Treatment” – Plan Int’l Behaviour promotion to prevent Malaria and treatment programme in White Nile State, Sudan Photographs: © Karl. Grobl. com & Malaria Consortium

Mobilising for Malaria A project of the Glaxo. Smith. Kline African Malaria Partnership implemented by The Malaria Consortium Purpose “To strengthen capacity in the north and Africa to mobilise political support and increase resource allocations for malaria” In Africa: Focus on countries where strengthened partnerships & political support needed - Cameroon, Benin and Ethiopia In Europe: Focus on countries with strong links to Africa - UK, France and Belgium Photographs: © Karl. Grobl. com & Malaria Consortium

GSK’s Malaria Vaccine – The objective üA vaccine that will protect infants and young children residing in malaria endemic regions from clinical disease and severe malaria resulting from Plasmodium Falciparum infection ü Safe and well-tolerated ü Compatible with standard EPI vaccines (DTPw , HBV , Hib, OPV…) ü Implementable through existing delivery programs such as the EPI ü Complements existing malaria control measures

History and Major Milestones of the RTS, S/AS Program Proof of Concept in challenge model (WRAIR) Proof of Concept in Gambian adults (MRC) Proof of Concept in children (CISM) Proof of Concept in infants (CISM) 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 00 01 02 03 04 05 06 07 Start of the program in Belgium GSK/MVI Agreement

Key efficacy data in young Africa children and infants CISM (Manhiça, Mozambique) N ~2000, 1 -4 years old Safe and well tolerated Highly immunogenic to CSP and HBSAg clinical malaria: severe malaria: hospitalized malaria: infection: 35. 3% (95% CI 22 -47; p < 0. 0001) 48. 6% (95% CI 12 -71; p = 0. 02) 30. 5% (95% CI 4 -50; p = 0. 032) 44. 9% (95% CI 31 -56; p < 0. 001) Vaccine efficacy in Infants 10 weeks old Infection : 65% 3 m FU Clinical malaria : 65% 3 m FU 18 m FU 6 m FU (Lancet 2007, 370: 1543 -51) N~200 Alonso et al, Lancet 2004; 364: 1411 -20 Alonso et al, Lancet 2005, 366: 2012 -18

Limited Serious Adverse Events [0 - 45 m] RTS, S/AS 02 A (n=1012) n % ( 95% CI ) SEVERE MALARIA DISEASE Serious Adverse events 235 21 -26 23 Cerebral malaria 2 0. 0 -0. 7 Severe malaria anemia 12 1. 2 0. 6 -2. 1 Severe malaria (others) 37 3. 7 2. 6 -5. 0 MORTALITY All deaths Excluded Trauma Malaria deaths 12 11 1 1. 2 0. 6 -1. 2 1. 1 0. 5 -1. 9 0. 1 0. 0 -0. 5 Control vaccines (n=1010) n % ( 95% CI ) 326 4 15 58 22 18 5 32 0. 4 1. 5 5. 7 29 -35 0. 1 -1. 0 0. 8 -2. 4 4. 4 -7. 4 2. 2 1. 4 -3. 3 1. 8 1. 0 -2. 8 0. 5 0. 1 -1. 1 Further indications of potential public health benefits Sacarlal et al presented at ASTMH 2007

Clinical Trial Partnerships for RTS, S/AS Northern Academic Institutions: • Prince Leopold Institut of Tropical Medicine, Belgium • University of Copenhagen, Denmark • University of Tuebingen, Germany • Bernhard Nocht Institute, Germany • University of Barcleona, Spain • Swiss Tropical Institute, Switzerland • London School of Hygeine and Tropical Medicine, UK • US Centers for Disease Control and Prevention, USA • Univeristy of North Carolina at Chapel Hill, USA • Walter Reed Army Institute of Research, USA Southern Academic Institutions: • Institut de Recherche en Science de la Sante, Burkina Faso • Kumasi Centre for Collaborative Research and School of Medical Sciences Kumasi, Ghana • Kintampo Health Research Centre, Ghana • Albert Schweitzer Hospital, Gabon • Kenya Medical Research Institute, Kenya • Wellcome Collaborative Research Programme, Kilifi, Kenya • University of North Carolina Project, Malawi • Centro de Investigacao em Saude de Manhica, Mozambique • Ifakara Health Research Development, Tanzania • National Institute of Medical Research, Tanzania

Phase III Efficacy Trial 11 centers in 7 countries representing different transmission settings, launching late 2008/early 2009 Up to 16, 000 children in 2 age categories: 6 weeks to 12 weeks (6, 000 minimum) 5 to 17 months (6, 000 minimum) Designed to provide Key safety and efficacy data to support file Full evaluation of relevant disease and public health endpoints to inform implementation planning If efficacy is confirmed in Phase III, the RTS, S/AS vaccine could have a major public health impact

Development Partnerships PATH/MVI’s mission is to accelerate the development of promising malaria vaccines and ensure their availability and accessibility in the developing world. The Bill & Melinda Gates Foundation's global health mission is to help to ensure that lifesaving advances in health are created and shared with those who need them most. The Walter Reed Army Institute for Research was where the first breakthrough in the development of RTS, S was made. It was through our partnership with WRAIR that RTS, S/AS has grown into a viable vaccine candidate.

Partnering for Full & Rapid Access to a Malaria Vaccine Scaling Up for Production: GSK has spent more than 24 years and US $300 m on developing a malaria vaccine, and building a manufacturing facility. Unprecendented, Streamlined Regulatory Strategy GSK, MVI-PATH, European Reg. authorities, WHO, African national regulatory authorities Implementation Strategy: Integration with EPI and other malaria control measures GSK and partners, international health authorities (WHO, UNICEF, GAVI) and national heath authorities GSK Bio Rixensart, Belgium

Synergy with Other Interventions? Efficacy against Severe Malaria 45% (95% CI 20 to 63) Lengeler C, Cochrane Database Syst Rev 2004 Infectious mosquito Infection of liver ITN , S S T R PTi I Parasitemia Clinical episodes Severe Malaria 49% (95% CI 12 to 71) Alonso P et al. , Lancet 2005; 366: 2012 50% (95% CI 8 to 73) Schellenberg D et al. , Lancet 2001; 357: 1471

A Malaria Vaccine That Sits On the Shelf Is Useless We Must Act NOW to Be Sure It Will Be Available and Widely Implemented As Soon As Possible