Malaria Vaccines: What we need for success [Acknowledge Stephen O’Brien, other distinguished guests] Good afternoon. Thank you for invitation BACKGROUND INFORMATION: Chairman: Stephen O’Brien MP (Conservative) Vice-Chairman: Dr Ian Gibson MP (Labour) Vice Chairman: Lord Rea (Labour) Vice-Chairman: Dr Evan Harris MP (Lib-Dem) Vice Chairman: David Drew MP (Labour) Treasurer: Ashok Kumar MP (Labour) Secretary: Eleanor Laing MP (Conservative) Coordinator: Susan Dykes Christian Loucq, MD Director, PATH Malaria Vaccine Initiative 8 July 2008 UK All-Party Parliamentary Malaria Group

Why I’m Here: To Answer Three Questions What is the PATH Malaria Vaccine Initiative (MVI)? Why a vaccine? What will it take? Why I am here today: To share my hope and excitement To answer three questions: What is MVI? Why a vaccine? What will it take?

A world free from malaria To accelerate the development of malaria vaccines and ensure their availability and accessibility in the developing world What is MVI? Our mission Our vision Focus: the parasite lifecycle One of three goals: a vaccine for infants and young children A world free from malaria Founded in 1999 Donors: Bill & Melinda Gates Foundation US Agency for International Development, ExxonMobil, private individuals

A world free from malaria To accelerate the development of malaria vaccines and ensure their availability and accessibility in the developing world Availability: Global access Regulatory & policy pathways Accessibility: Preparing countries for the vaccine introduction Decision-making framework Two other goals (from development to DELIVERY): Availability: licensed for use, financed, Accessibility: adopted by countries, integrated into existing systems How we work: Vaccine INVESTOR Partnerships Collaboration: Global Vaccine Portfolio A world free from malaria

MVI: A global program of PATH WHAT IS MVI? A global program of PATH: International health NGO Track record of SUCCESSFUL vaccine development

Why a Malaria Vaccine? Why a vaccine? HISTORICALLY: Most efficient way to prevent disease TODAY (Version 1.0 in 2012): A partially effective vaccine will reduce deaths and illnesses TOMORROW (Version 2.0 by 2025): An 80% effective vaccine will help ERADICATE malaria PHOTOS Salim with sick child (malaria) Girl with vaccination card (let’s add malaria to the list)

Why a Malaria Vaccine? Age Distribution of Severe Malaria 0.14 0.12 0.1 0.08 0.06 0.04 0.02 Gupta et al., Nature Medicine 5: 340-342, 1999 Sukuta Kalifi N Kalifi S Siaya Proportion Affected Why a Vaccine? Infants at most risk Under-Fives altogether Pregnant women come next In Kintampo, Ghana, where one of our partner trial sites is located, each person is bitten – on average – 300 times each year by infected mosquitoes. 1-2 mos 3-4 mos 5-6 mos 6-12 mos 1 2 3 4 5 6 7 8 9 Age group 7

Targeting the Parasite Lifecycle If the vaccine targets…. Its goal is to…. Pre-erythrocytic Stage Prevent infection Blood-stage Reduce clinical disease Sexual transmission blocking Prevent the spread of parasites by mosquitoes THE ‘NEXT GENERATION’ GOAL 80 PERCENT HOW DO WE GET THERE? Target different stages Explore different approaches Combine them together

Research and Development Strategy HOW DO WE GET THERE? Robust strategy Exciting advances Strong partners from discovery, through development AND delivery KEY ELEMENTS (EXPLAIN) New antigens New platforms New adjuvants and mixtures Evaluation technologies BACKGROUND Antigen: manipulate protein in lab so body thinks it is the real thing Platform: targeted delivery vehicle Adjuvant: clean dirt (chemical) Evaluation: assess effect BEFORE human test

Product Candidates Research Programs Targets P. vivax Pre-erythroctyic Construct Selection Process Development Final Formulation Toxicology Phase 1a Phase 1/2a Phase 1b Phase 2b Sanaria PfSPZ GSK RTS,S AS01/AS02 Product Candidates Targets P. vivax Pre-erythroctyic (liver) Pre-erythroctyic (liver) ICGEB/BBIL PvRII Monash MSP4 GenVec Ad5-CSP: LSA1:Ag2 + Ad5-MSP1: AMA1 LaTrobe MSP2 ISA720 WHAT DO WE HAVE TODAY (EXPLAIN) Potential products Research programs Blood-stage MVDB AMA1-C1 ISA720 Research Programs Adjuvanted Recombinant Proteins Viral Vectored Live Attenuated (weakened) WRAIR/GSK AMA1 AS01/AS02

RTS,S Clinical Research Center Network IRSS - Centre Muraz KHRC, Kintampo KCCR, Kumasi KEMRI - Kisumu HAS, Lambarene KEMRI - Kilifi JMP, Korogwe IHDRC, Bagamoyo KCH, Lilongwe RTS,S: Closest to use First-ever Phase 3 Early development by GSK Biologicals and US Walter Reed Army Institute of Research Network of 10 trial sites (11 facilities) in 7 countries NEED Phase 3 to assess efficacy in diverse settings. BACKGROUND: Burkina Faso, Gabon, Ghana (2), Kenya (2/3), Malawi, Mozambique, and Tanzania (2)]. CISM, Manhiça RTS,S MVI-GSK Program in Africa

WHO Vaccine Prioritization Vaccines that may be licensed by 2012 (WHO SAGE, November 2007) WHY a partially effective vaccine? The whole world cares: Top bar, LONGEST, is malaria Many endemic countries want it: SAVE hundreds of thousands of lives Weighted priority score based upon expert opinion

Sanaria: A Different Approach Targets the whole parasite Uses a live, attenuated parasite ANOTHER APPROACH (version 2.0????) Harvest sporozoites from salivary glands of irradiated mosquitoes DISSECT (die-sect) Nussenzweigs and Vandenberg Human trial in early 2009

Challenges: What will it take? No vaccine against a parasite No known correlates of immunity No “market” CHALLENGES to DELIVERING vaccines: Scientific: 6,000 proteins Business: No market (in traditional terms) Financial: Expensive (half billion dollars) Political: Long-term commitment is needed (especially by donors)

What will it take? Strong partners Strong, committed partners will make it happen SCIENTISTS, like Salim in this picture BUSINESSES, like GSK Biologicals, Sanaria, GenVec PARENTS, who volunteer their kids POLICYMAKERS, making informed decisions DONORS, like the Gates Foundation, but WE NEED OTHERS

What will it take? Sustained commitment To OVERCOME malaria, we need SUSTAINED COMMITMENT YOU can help by adding your voices…. Expand existing interventions AND make them better Invest in new tools, VACCINES Push AND Pull

Partners Today … and Tomorrow Key partners in the development and delivery of vaccines DFID and the UK government have already made a difference NEW research strategy is promising PUSH and PULL funding are both needed

What can you do? Support investments in malaria control today Advocate now for investments in the tools for tomorrow And …