AIDS Vaccines Advancing Development through Innovation

1. AIDS Vaccines Advancing Development through Innovation Frans van den Boom Vice President IAVI European Programmes 24 October 2007 Helsinki, Finland

2. Understanding global inequalities Private health spending Malaria cases 2 Dorling D (2007) Worldmapper: The Human Anatomy of a Small Planet. PLoS Medicine 4(1)13-18

3. Global, neglected and most neglected diseases (WHO & MSF) 3 Most neglected diseases(e.g. dengue, Chagas) World pharmaceutical market(>$600 bn in 2005) Neglected diseases(e.g. AIDS, malaria, tuberculosis) Global diseases(e.g. measles, diabetes)

4. Consequently in the last 30 years <1% of the developed drugs were for LDC specific diseases

5. R&D for neglected diseases: PPPs are changing the field • PPPs currently manage ¾ of neglected disease drug development projects • The private sector is making more independent investments in neglected disease R&D • A quarter of neglected-disease R&D is now being undertaken independently by large companies • Four large pharma companies have founded formal neglected- disease divisions since 2000 Source: Moran (2005) A breakthrough in R&D for Neglected Diseases: New Ways to Get the Drugs We Need. PLoS Medicine 2(9):e302.

6. Why do we need New Prevention Technologies?Our tools today are not enough to stop AIDS • Over 39,5 million people infected with HIV and • 11,000 new infections daily • A comprehensive response is needed: • Deliver for today – better use of tools • Prevent further spread of the virus • Treat and care for those already infected • Mitigate social impacts • Develop better tools for the future • Invest in innovation for new technologies(drugs, diagnostics, microbicides, vaccines) Better prevention tools – particularly AIDS vaccines - are critical for the affordability and sustainability of our commitments to universal access Source: UNAIDS 2006 Photos: WHO/UNAIDS

7. 30% efficacy, 20% coverage 5.5 million 50% efficacy, 30% coverage 17 million 70% efficacy, 40% coverage 28 million New adult HIV infections in low- and middle-income countries A vaccine could save millions of lives Total new infections averted by an AIDS vaccine between 2015-2030 IAVI impact forecasting; Policy Brief #10, November 2006

8. Who needs an AIDS vaccine? • All those who are at risk of HIV infection • Especially people in the countries that are hit hardest by the AIDS epidemic • Especially women, who need tools that they can control to protect themselves • Especially teenagers and young adults, before they are sexually active or initiate the use of intravenous drugs Global demand for an AIDS vaccine could reach 80 million doses per year* IAVI demand forecasting; Policy Research Working Paper # 15, 2007

9. What is happening across the AIDS vaccine field?

10. Around the world, 23 countries are conducting AIDS vaccine trials (around 30 vaccine candidates in development)

11. AIDS Vaccines in Clinical Trials - 2007 Viral Vectors- Adenovirus Ad-5 (Clade B) Merck Ad-5 (Clades A,B,C), [DNA] NIH-VRC Ad-6 (Clade B) Merck Viral Vectors- Pox Canarypox (Clade B/E), gp120* Aventis MVA (Clade C) IAVI-Therion MVA* (Clade C) IAVI-ADARC; MVA (Clade B),[fowlpox] Therion MVA (Clade B),[DNA] GeoVax MVA (Clade A/E), [DNA] WRAIR MVA (Clade B’/C Changchun Baike Fowlpox (Clade B)[MVA] Therion NYVAC (Clade C)[DNA] EuroVac Vaccinia (Cocktail) St. Jude’s Viral Vectors- Other VEE (Clade C) AlphaVax [formerly IAVI] AAV-2 (Clade C) IAVI-TGEN DNA vectors Clade C, IAVI-ADARC Clade B-minigenes Epimmune Clade B-nuclear anchor FIT Biotech Clade B, MVA* GeoVax Multiclade-A,B,C, Ad5* NIH-VRC Clade B- Micro particle, gp140* Chiron Multiclade, gp120* U. Mass Multiclade-ABC, MVA* Karolinska Clade C Johns Hopkins Clade B’?C Changchun Baike Clade B/C, NYVAC* EuroVac Clade B- IL12, IL-15, peptide* Wyeth [ ] = prime * = boost

12. AIDS Vaccines in Preclinical Pipeline - 2007 In trials 2007-2009 Ad 35 prototype NIH-VRC Ad 35 IAVI-Crucell Chimeric Adeno Harvard-Crucell VSV Wyeth Measles GSK MVA SAAVI; WRAIR • NIAID/CHAVI • Chimeric Adeno Vectors • BCG • VSV • CAVD BMGF • Adeno: Chimeric and Ad-11 • Pox: NYVAC, MVA • Low sero-prevalent AAV • Reovirus • Newcastle Disease • HIV/VEE Chimeras • HIV/VSV Chimeras • BCG • IAVI Vector Program • Sendai • CMV • Simian Adeno (GSK) Blue = IAVI program

13. The current pipeline is inadequate Only hypothesis currently tested in pipeline is cell-mediated immunity

14. Political commitment is improved "Whether it takes us 15 years, 20 years, 25 years to get an AIDS vaccine, it is what will break the back of the disease." - Melinda Gates

15. More resources are being invested …but more still are needed, especially from Europe Annual average by country relative to national wealth (2003-2005) Investment in AIDS vaccine R&D % of GDP (x10-3) Total over 2005 = US$759 mn Country United States 4.0 – 5.0 (none) 3.0 – 4.0 Ireland 2.0 – 3.0 Canada South Africa Netherlands 1.0 – 2.0 Norway United Kingdom Denmark Sweden 0.5 – 1.0 Australia Brazil China Finland France Germany India Italy Japan Russia Thailand < 0.5 Based on a 2006 study by the HIV Vaccines and Microbicides Resource Tracking Working Group; full report available at: www.hivresourcetracking.org. The study reviewed national, not sub-national or provincial, public sector data. Cuba is not captured as no GDP data is available. Estimates of 2005 investment include NIH CHAVI funds.

16. Registration Clinical Data Analysis Full Development Studies in 100-300 Patients (Phase II) Candidate Medicine Tested in 3-10,000 Patients (Phase III) Large Amounts of Candidate Medicine Synthesized Extensive Safety Studies Candidate Studies in Healthy Volunteers Phase I Formulations Developed Exploratory Development Synthesis of Compounds Early Safety Studies Project Team and Plans Screening Discovery Developing a high-quality medicine is a complex and expensive road $ $ $ $ $ $ $ $ $ $

17. What is IAVI’s role?

18. IAVI’s mission is to ensure the development of safe, effective, accesible, preventive HIV vaccines for use throughout the world

19. IAVI, public–private product development partnership since 1996 • Research and development • Fill the gap between between public sector basic research and commercial product development • Develop vaccine candidates, prioritize the most promising ones and move them into clinical trials • Policy and advocacy • Ensure political and financial commitment • Create a supportive environment for research • Prepare for global access • Engage developing countries • Building capacity for R&D • Contribute to sustainable development of health infrastructure • Involve communities, policy makers, politicians, media Access & uptake R&D Clinical trials Production Health & other systems Political will & finance

20. IAVI’s niche in AIDS vaccine R&D Filling the gap between public sector basic research and commercial product development Public Sector Biotech Venture Capital Biotech Pharma Preclinical and Clinical Trials Basic Research Applied Research Vaccine Design Early Product Devel. Advanced Devel. Large Scale Efficacy Phase IIa Small Animal NHP Phase I Phase IIb Phase III

21. IAVI R&D Resources • New Technology Assessment • Product Development Infrastructure • Network of Partner-Sites in Developing World • IAVI Human IAVI Immunology Lab • Vaccine Development Lab Neutralizing Antibody Consortium (NAC) Vector Design Consortium (VEC) Control of HIV/ SIV-Live Attenuated Consortium (LAC)

22. A global R&D network, with a particular focus on developing countries

23. Partnership with developing countriesIAVI’s clinical trial network IAVI India Pune-NARI, India Kangemi and KNH-KAVI, Kenya Chennai-TRC, India Entebbe-MRC, Uganda IAVI East Africa Masaka-MRC, Uganda Kilifi-CGMRC, Kenya Kigali-PSF, Rwanda Lusaka-ZERHP, Zambia Medunsa, South Africa Cape Town-DTHC, South Africa IAVI Southern Africa Soweto, South Africa

24. Product Development: Prioritization of Candidates Percent Positive Responders Geometric Mean: SFC/milion and Range of Responses IAVI has 13 clinical trials completed; 4 clinical trials ongoing Total of 907 volunteers enrolled in PI and PII trials in 11 countries Vaccine response rate in vaccinees at peak post vaccination timepoint per trial; Core Laboratory generated data; GMT SFC and min max SFC for responders; background subtracted per 106 PBMCs.

25. IAVI Clinical Research Studies:Prepare for Efficacy Trials & Inform Vaccine Design P Fast, M Price, N Ketter, J Gilmour, etal

26. The IAVI model: working with developing countries • Use a “development” approach to R&D • Ensure that vaccines will be available, accessible and used • Ensure sustainable research capacity and knowledge building • Ensure the participation of national stakeholders • Address social and political context related to research in different cultural settings • Promote national ownership and in-country commitment • Bring their voices to the global call for an AIDS vaccine • Mobilize countries as integral to the process • Supporting strong and well-informed developing country voices Industrial-style R&D within the context of sustainable development and social responsibility

27. An example:(1) Site development Uganda Virus Research Institute [BEFORE] Site of Proposed UVRI-IAVI Lab & Clinic

28. UVRI-IAVI Lab & Clinic in Entebbe, Uganda [AFTER] • Lab/Clinic built • Laboratory:Validated CMI assays, GLP training • Accredited and now BMGF/CAVD reference lab • Clinic: Multiple Phase 1 HIV vaccine trials: Accelerated approval and accelerated enrolment vs. historical controls • Expansion: Field sites doing incidence and other clinical studies in preparation for future efficacy trials

29. An example:(2) Training and education • Vaccine Literacy • Education programmes for: • Healthcare workers • Counselors • Community Advisory Board • Community Workers

30. HPV vaccines can facilitate future introduction of AIDS vaccines – infrastructure and lessons Targeting adolescents/pre-adolescents before they are sexually active Challenging the paradigm of delayed introduction in the developing world IAVI and PATH agreed in early 2007 to a collaboration around PATH’s “HPV Vaccine: Evidence for Impact” project An Example:(3) Preparing for vaccine delivery – lessons from HPV vaccine introduction

31. PATH and IAVI strategic partnershipIntroducing HPV vaccines in the developing world:bridging reproductive health with the global response to aids • Objectives Country Introduction • Implementing Research • Testing Key aspects • Strengthening Decision-making Policy Analysis • Market, supply and demand analysis • Develop decision-making tools Global Advocacy • Coalition building • Incorporating HPV vaccine in development agenda • South-South cooperation • Shared challenges for • HPV and AIDS vaccines • Targeting Adolescents • Sexuality and Stigma • Delivery Strategies • Complex Messages • Stakeholder Support • Demand and Financing • Rapid Introduction • Women and Reproductive Health

32. While important progress is being made, equally important challenges remain Issue What it means • HIV hyper-variability • Immune correlates of protection are still unknown • Relevant animal models lacking • Clinical trials long and costly • We are tackling a moving target • Need to test in people • Success will take time Scientific • Long term effort requires long term, high level global commitment - leading to action • Market incentives for industry activity lacking • Ethical, regulatory, IP issues • Health systems challenges • Until recently not a priority; we need sustained political support • Build private sector engagement • Optimize environment for safe, ethical trials Policy & Political

33. IAVI’s Innovation Fund Your ideas Breakthrough technologies • Novel immunogens e.g. bNAb, host targets • Target novel immune mechanisms e.g. innate immunity • New delivery modalities e.g. replicating vectors, mucosal delivery • New ways to address key challenges – e.g. from systems or computational biology • Technologies that optimize existing candidates • Adjuvants and formulation • Antigen optimization • Delivery technologies • Prime-boost combinations • “Enabling technologies” • High throughput screening methodologies • High throughput immunogen design • Our offer • Seed funding • Non dilutive, targeted grants specifically designated for high-risk/high-reward technologies not funded through traditional HIV funding sources; fast approval process • Platform validation • Feasibility of use in HIV vaccine R&D • Accelerated regulatory pathways • Lower risk of investment in early phase technologies • Opportunity for longer-term collaboration • Funding & partnership over the long haul • IAVI experience (and infrastructure) with regulatory approval and clinical trials including in developing countries

34. IAVI’s public policy research activities • Activity The ”business case” • Modeling the impact of AIDS vaccines • Analyzing the potential demand for AIDS vaccines Supporting R&D • Regulatory and ethical approval for AIDS vaccine trials • An advance market commitment (AMC) for AIDS vaccines • Collateral benefits of vaccine trials The wider context • AIDS and the Millennium Development Goals (MDG) • Policy research and advocacy on gender issues • Why are these important? Accelerate R&D and future access • Ensure adequate funding and human resource capacity • Enhance global political and financial support • Increase private sector and PPP engagement • Build national commitment to AIDS vaccine research • Build support for trials and future demand

35. The road to a vaccine is long … but there are many achievements on the way, in the South • Medical Ethical committees • Standards of Care for volunteers • Education for communities and journalists • Voices from the south in the global arena • And many others … Healthcare workers who received training National policies for HIV vaccine research 11 clinical labs & sites in Africa and India 27000 people who received VCT Community and gender advisory boards

36. And in the North 3 scientific consortia with scientists from across the world Global HIV Vaccine Enterprise Innovation Fund Resource tracking Political commitment Financial commitment

37. We need your support … • To ensure that political commitment to AIDS vaccine R&D is sustained … for as long as needed • To build an supportive environment with the right policies • To raise sufficient financial support for AIDS vaccine R&D for IAVI and for the field • To address the remaining key scientific challenges • To continue engaging developing countries and build sustainable capacity for research • With as ultimate aim to accelerate the development of an AIDS vaccine that is accessible to all who need it

38. IAVI’s partners in Europe Industry - Berna, Switserland - Crucell, Netherlands - Cobra, UK - GSK Biologicals, Belgium - Bioption, Sweden - FIT Biotech, Finland - IDT, Germany - Transgene, France AIDS organisations - AIDES, France - AIDS Fondet, Denmark - Aidsfonds, Netherlands - Deutsche AIDS Stiftung, Germany - El Grupo De Trabajo Sobre Tratamientos Del VIH (gTt), Spain - Finnish AIDS Council, Finland - HivNorge, Norway - National AIDS Trust, UK - Noah’s Ark, Sweden - SENSOA, Belgium Vaccine development • Academia • - Centre d’Immunologie de Marseille-Luminy, France • Imperial College, London, UK • Karolinska Institute, Sweden • Medical Research Council, Oxford, UK • St. Georges University of London, UK • University of Amsterdam, The Netherlands • University of Oxford, London, UK Advocacy & mobilization 20

39. IAVI gratefully acknowledges the support of our donors