1. Sustainability: The R&D Pipeline for Neglected Disease Vaccines Elizabeth L. Ponder, PhD May 4, 2011 Global Vaccines 202X: Access, Equity, Ethics 2-4 May 2011 The Franklin Institute Science Museum Philadelphia, USA

2. BIO Ventures for Global Health (BVGH) We have a unique perspective. We look at health problems facing poor countries through a dual lens: Expertise in IndustryExpertise in Global Health Mission: BIO Ventures for Global Health is an independent, non-profit organization whose mission is to save lives by accelerating the development of novel, biotechnology-based drugs, vaccines, and diagnostics that address the unmet medical needs of the developing world.

3. The Global Health Primer provides a landscape analysis for neglected disease products Updated online database for 17 neglected diseases: www.bvgh.org/ globalhealthprimer.aspx www.bvgh.org/ globalhealthprimer.aspx Covers drugs, vaccines, and diagnostics Highlights product needs and opportunities

4. There are 12 approved and 160 vaccines in development for neglected diseases 106 Products in Clinical Development

5. Preventive vaccines receive the largest portion of neglected disease R&D funding G-FINDER ANALYSIS: Mary Moran & Javier Guzman, Policy Cures

6. Neglected disease vaccines are in development by 169 organizations representing 35 countries Developer TypeNumber of Organizations Academic/Research Institution67 Biopharmaceutical Company52 Government29 Product Development Partnership (PDP) 17 Other4 Total169 80 55 12 10 6 Number of Developers per Country

7. Looking across the vaccine landscape, several trends emerge: Newer vaccines in development for neglected diseases are increasingly scientifically complex due to new technologies and targeting more challenging organisms Proof of concept trials for new vaccines are progressing, but scientific learning beyond efficacy from these efforts has been minimal A lack of financing options, clear policy statements, or WHO prequalification of an approved vaccine severely limits access Early Innovation Clinical Proof of Concept Approval and Access

8. Early-stage neglected disease vaccines focus on newer technologies No approved vaccines in humans In use in approved vaccines

9. Parasitic diseases represent the majority of neglected diseases but the minority of products Unicellular parasitic diseases: Malaria Sleeping sickness Chagas disease Leishmaniasis Multicellular parasitic diseases: Schistosomiasis Soil transmitted helminthiasis Onchocerciasis Lymphatic filariasis

10. Proof of concept studies are advancing but still have a long way to go DiseaseProof of Concept R&D Investment (G-FINDER) ETECPartial protection from Cholera vaccine$15.6 million DengueData expected Q4 2012$115.7 million HIV30% efficacy in Phase III trial$1,374 million Malaria 30-50% efficacy in a series of Phase II trials $116.4 million Schistosomiasis Phase III trial as adjunct to MDA in progress $9.5 million Shigella On market vaccine in China provides ~60% efficacy $14.0 million TuberculosisBCG protects against systemic TB$187.0 million PATH and BVGH (2011) The Case for Investment in Enterotoxigenic Escheriscia coli Vaccines. Clemens JD et al. (1988) J Infect Dis 158: 372-377. Peltola H et al. (1991) Lancet 338: 1285-1289. Rerks-Ngarm S et al. (2009) NEJM 361: 2209-20. Casares S et al. (2010) Vaccine 28: 4880-94. PAHO et al. (2004) “Progress in Shigella vaccine development.” in Vaccines: preventing disease & protecting health. Colditz GA et al. (1994) JAMA 271: 698-702 WHO (2004) Weekly Epidemiological Record 79: 27-38 Moran M et al. (2011) Neglected Disease Research and Development: Is the Global Financial Crisis Changing R&D? Policy Cures.

11. Neglected disease vaccines challenge the traditional industry model for clinical evaluation As products fail, or show only partial efficacy, how do we decide what to do next? Traditional Industry Model: How can we help vaccines that will fail, fail faster? For Neglected Diseases: How can we help vaccines that will fail, not just fail faster, but also fail smarter? How can we maximize learning from vaccine trials with partial efficacy?

12. Clear policy and financial support improve vaccine access DiseaseProduct (Company) Initial Approval Year of WHO PrequalificationGAVI supported?Current Use Pneumococcal Disease Synfloris (GSK) Europe, 2009 2009 Yes, AMC 44 countries as of 2009 Prevnar 13 (PCV13 – replacement for PCV 7 which was approved in the U.S. in 2000; Pfizer) U.S., 20102010 Rotavirus RotaTeq (Merck)U.S., 20062008 Yes 23 countries as of 2009 Rotarix (GSK)U.S., 20082009

13. Clear policy and financial support improve vaccine access DiseaseProduct (Company) Initial Approval Year of WHO PrequalificationGAVI supported?Current Use Pneumococcal Disease Synfloris (GSK) Europe, 2009 2009 Yes, AMC 44 countries as of 2009 Prevnar 13 (PCV13 – replacement for PCV 7 which was approved in the U.S. in 2000; Pfizer) U.S., 20102010 Rotavirus RotaTeq (Merck)U.S., 20062008 Yes 23 countries as of 2009 Rotarix (GSK)U.S., 20082009 Cholera Dukoral (SBL Vaccin, Sweden) Sweden, 1991 2001 No Limited, need more data on roll in outbreaks Shanchol (Shantha Biotechnics, India) India, 2009- mORCVAC (VaBiotech, Vietnam) Vietnam, 2009 - Typhoid Vivotif (Crucell) Switzerland, 1981 - No, shortlisted for future support In travelers and select endemic regions Typhim Vi (Sanofi- Pasteur) U.S., 1994-

14. Key needs for future neglected disease vaccine development include: A focus on parasitic disease vaccine development to understand the technical feasibility and potential health impact Increased investment in the integration of scientific research questions with efficacy studies for vaccines to maximize return on public investment More operational and clinical research on existing vaccines to support the development of clear policy statements, accelerate WHO prequalification, and inform decisions on new product needs Early Innovation Clinical Proof of Concept Approval and Access