HIV Vaccine Research & Development

1. HIV Vaccine Research & Development Understanding the landscape – A Funders’ Briefing Mitchell Warren Executive Director, AVAC 29 March 2012 Funders Concerned About AIDS

2. About AVAC • Founded in 1995 • Use education, policy analysis, advocacy and a network of global collaborations to accelerate the ethical development and global delivery of new HIV prevention options as part of a comprehensive response to the pandemic

4. Soundtrack for the Search for an AIDS Vaccine • We’re on a road to nowhere • If you don’t know where you’re going, any road will take you there • It is a long and winding road Source: AVAC Report 2007: Resetting the Clock

5. Research is… • “Research is four things: brains with which to think, eyes with which to see, machines with which to measure and, fourth,money.” Albert Szent-Györgyi, 1937 Nobel Laureate in Medicine

6. A Three-Part Agenda for Ending AIDS • Deliverproven tools for immediate impact • Modelsuccessful programs • Mobilizedemand for new tools • Reprogramresources for impact • Fundevidence-based scale-up • Testing • Male Circumcision • Treatment GOAL: A sustained decline in HIV infections (now at 2.7 million/year) • Demonstrateproven tools for immediate impact • Planfor rollout in different settings • Prioritizeuse of tools for greatest impact • Pilotto guide real-world implementation COMBINE • PrEP • Microbicides • Developlong-term solutions to end the epidemic • Sustainresearch funding to capitalizeon new scientific insights • Vaccines • Functional Cure End Years to Impact Zero to 5 5 to 10 10 to

7. Highlights from 2011 in HIV Vaccines R&D In May 2011, the Pox-Protein Public Private Partnership or “P5” (formed by Sanofi Pasteur, Novartis, US NIH, Gates Foundation, the US MHRP and the HVTN) debuts, designed to move from the RV144 Thai prime-boost vaccine trial results to a potentially licensable product for Thailand and elsewhere. In 2009, the RV144 Thai vaccine was the first ever to demonstrate a modest effect of 31.2% in preventing HIV infection. In September 2011, immune responses predictive of risk in RV144 trial identified. In August 2011, the HVTN 505 Phase II trial of a DNA-Ad5 combination expands its scope to include an investigation of whether the experimental vaccine regimen prevents HIV infection. More than two dozen phase I & II trials are ongoing in 20+ countries worldwide. Promising antibody and animal studies are continuing. Follow-on studies from RV144 in South Africa and Thailand in devlelopmemt. 2011 Series of ongoing discoveries of new neutralizing antibodies, that provide potential new targets for AIDS vaccine development JanuaryFebruary March April May June JulyAugust September October November December

8. Ongoing Phase I/II and II Preventive AIDS Vaccine Clinical Trials HVTN 205US, Peru Phase II trial to assess safety of DNA and MVA vaccines and immune responses of participants to see if these vaccines are helpful in fighting HIV infection. Q3 2014 HVTN 505 US Expected 2013 Phase IIb trial to assess ifDNA prime/rAd5 boost vaccine regimensignificantly reduce viral load in individuals who become infected with HIV. HVTN 078Switzerland Phase I/II trial to assess the safety and immune response in the mucosa of the vector vaccines NYVAC-B and the rAd5. TaMoVac1Tanzania, Mozambique Ongoing Phase I/II trial to assess the safety and immune response of DNA priming and MVA boosting and to develop further HIV vaccine trial capacity building in Tanzania. HVTN 083US Ongoing No effective HIV vaccine is available today; however, more than two dozen phase I & II trials are ongoing in 20+ countries around the world, including follow-on studies from recent large-scale trials. Phase I/II trial to assess the safety and immune response of an adenovirus-based HIV-1 vaccine regimen. HVTN 084 Ongoing Brazil, Peru, Switzerland, US Phase I/II trial to assesses the safety and immune response of two Ad5 adenoviral vector vaccines.

9. Investing in HIV Vaccine Research & Development Annual investments in HIV vaccine R&D 2000 – 2010 (US$ millions) 961 933 868 868 859 759 682 548 547 366 327 * Commercial sector estimates not available for years 2000 to 2004. For years available commercial funding figures are estimates based upon a review of HIV vaccine programs at each company. ** Other includes all national public sector funding apart from funding from the US and Europe.

10. HIV Vaccine Expenditures 2010 US$ 859 million was spent on HIV Vaccine R&D in 2010: what was it spent on? US$ 8,590,000 spent on advocacy & policy development in 2010 (1% of total) US$ 51,540,000 spent on cohort & site development in 2010 (6% of total) US$ 231,930,000 spent on basic research in 2010 (27% of total) US$ 214,750,000 spent on clinical trials in 2010 (25% of total) US$ 352,190,000 spent on pre-clinical research in 2010 (41% of total) Basic research Pre-clinical research Clinical trials Advocacy & policy development Cohort & site development

11. Bottom line • There remains an urgent need for new HIV prevention options, including an AIDS vaccine • An AIDS vaccine is possible • Now is the most exciting and promising – and increasingly complex – time in AIDS vaccine research • Investments in AIDS vaccine R&D today is an investment in the future and in ending the epidemic • It’s not just about the “product”