1. Stakeholders meeting for priority medicines for Europe and the world Role of Public Private Partnerships 4 October 2004 Brussels Dr. Frans Van den Boom, MBA Executive Director Europe

2.  High incidence and prevalence of infectious diseases in developing countries  Enormous impact (life expectancy; economic growth; security threat)  Market mechanism works: no private sector investments in absence of a market  Insufficient product development efforts for poverty related diseases  15 – 20 year delay before products are made available for poorest countries Global Problem

3. >70 million HIV infections >28 million AIDS deaths 0 cured 14,000 new infections/day, >95% in developing world The world needs an AIDS vaccine Photos by WHO/UNAIDS

4. World Impact By the year 2050 the world will have 480 million less people as a result of the AIDS epidemic…

5. Opportunities and challenges in global health

6. New Interest in Global Health  Window of opportunity u United Nations: Security council, Commission on Macro Economics and Health, UNGASS, Priority Medicines u Global Fund u G8 u EC Plan of Action on Poverty Related Diseases u President’s Bush 18 b initiative u Increase in # PPP’s u Increased industrial interest and involvement u Increased resources (public and private, notably BMGF) u Increased involvement of developing countries (e.g. EDCTP)  Health not defined only in technical terms, but also in terms of: u Economics u Moral / Humanitarian imperative u Security issue u Development issue  Global Health as well as global health interventions defined as global public goods u Repositioning of private and public sector

7. Challenges in global health  Too little effort to tackle developing countries problems (90-10 gap, market mismatch)  Lack of infrastructure in developing countries  Too little involvement of developing countries  Emphasis very much on treatment  Insufficient resources  Competing priorities (bio-terrorism, SARS)  Sustainability of effort (GAVI, GF, CVF, PPP’s)  Unease between public and private sector  Humanitarian imperative vs business imperative  No global health R&D funding mechanism  Uncoordinated effort and counterproductive competition (national/regional vs global)  Lack of political will

8. AIDS vaccines account for less than 1% of total global spending on health R&D AIDS vaccine R&D US$540-570 million Total health-related R&D US$70 billion+

9. Estimated Worldwide HIV Expenditures* (2002 in Millions of Dollars) Research & Development 20-25% Prevention & Care 75-80% Vaccines $540-570 M (LDC effort <$40–50M) Prevention Care Basic research, therapeutic & other * Source: IAVI estimates & AIW II Global Total = $20+ Billion

10. Global Expenditures on HIV Vaccines ( Success or Failure ?) 19942002 Product Development $ 20 M(?$ 70-90 M) Developing Country Specific $ 1-2 M(?$ 40-50 M) Total$ 125 M$ 540-570 M Source: IAVI Estimates

11. Challenges (continued)  PD is expensive (~ US$ 800 million)  Science is complex: high risk investments  Numerous IP challenges (e.g. Numerous broad ‘umbrella’ patents and vaccine component patents; Stacking of patent royalties)  Access issues ( Pricing, Financing, Manufacturing, Delivery, Acceleration of regulatory consideration, Provision of non negligent liability protection )  Decreased attention for vaccines (global market for drugs: $ 450 billion for vaccines:$ 6 billion)

12. Source: MVI, Patricia Atkinson Roberts

13. Delivery device A modern vaccine is protected by multiple levels of IP licensed from multiple partners Antigen Adjuvant Excipient ExpressionDNA seq Vehicle Immunostim vaccine Platform/ process Source: Martin Friede, WHO

14. PPP as mechanism to address problems:

15. Necessity of new mechanisms  Market Issue: Private Industry doesn’t have the incentives; but needs to be included as they have all of the skills  Public sector is best at funding “R” rather than ”D” and is often national in its outlook  UN agencies do not have the flexibility/agility to rapidly move with different corporate partners  Response has to be global: engaging the world’s best scientists, companies, testing sites

16. Global Product Development Public Private Partnerships in Health  Partnerships seen as the way to overcome market and government failure  Interest in experimenting with partnership strategies and mechanisms that might overcome these failures to produce global public goods  Global advocacy has resulted in more € from public sector and legislative proposals to promote R&D (tax incentives)

17. i a v i Efficacy Trials Licensed vaccine Basic Research Applied Vaccine Research Vaccine Design Project management Regulatory affairs, QA, QC Phase I/II Pilot manufacturing Process development International clinical trials infrastructure Scale-up manufacturing The Road to an AIDS Vaccine

18. Product Development PPP’s  Multi-candidate/portfolio approach  Focus on translational research: translate basic research discoveries into products that can be tested in humans  Bring industrial expertise into the public sector and small biotech (QA/QC; regulatory expertise; process development and manufacturing; project management; GLCP; GMP; data management; IP management; business rigor to cancel struggling projects early)  Primary objective: public health rather than commercial goal  Want to get there as fast as possible, without compromising safety  Not tied to any one company: interface with other organisations in the R-D-A continuum  Have a global perspective  Work with developing countries and build sustainable capacity  Focus on product development, manufacturing and access

19. Industrial involvement in IAVI programme  Targeted Genetics (rAAV)  Bioption (SFV)  Therion (MVA)  IDT (MVA)  Berna (salmonella)  Cobra (DNA)  Crucell (Adeno)

20. IAVI R&D Team Project Management Business Develop. & Strategic Planning Research & Design Development & Mfg. Medical Affairs Regulatory Affairs GSK, CSL, Aventis, Hale & Dorr, Holland & Knight, Merck, NIH, Scripps, Penn, Cornell, Oxford, Harvard Wyeth, Connaught, GSK, Merck Aviron, Aventis, Chiron,VaxGen, Merck FDA, EMEA, WHO, Biologics Consulting, GSK, Wyeth, Genetics Institute

21. Create incentives for Industrial Investment  Active dialogue with vaccine industry  Political support for tiered pricing  Create credible LDC market through vaccine purchase funds  Reduce R & D costs by directly financing research & clinical testing  Target other areas of industry concern such as regulatory simplicity & liability  Active collaborations working with World Bank, EC & individual OECD governments as well as other Public- Private Partnerships

22. Shared investments – shared ROI?  Public sector u research + clinical trial infrastructure + purchase commitment + delivery system  Private sector u Technology + skills + IPR  Developing countries u 10.000’s of volunteers u Political pressure u Potential market

23. Everybody could be left better off  The people / end users  The developing countries: u Better health (infrastructure) u Better science u Better technologies  Private sector u Recoup investments u Create new markets (health – wealth paradigm) u Acceptance of business model  International community u Security and stability

24. Ten years ago @ Bellagio (circa 1994)  Vaccine pipeline limited  Little investment in products by public or private sectors (market failure or market effectiveness?)  Little public interest in HIV vaccines  No vaccine ever tested for efficacy  Limited attention to vaccine issues specific to high incidence countries: no designed African/Asian vaccines  Few vaccine advocates  No political leadership for vaccines

25. To help with some of these challenges, IAVI established as public- private partnership in 1996  Focus on developing country needs—as partners  Appreciate importance of industry; work closely with them but take R&D risks they cannot take  Focus on applied product development  Maintain flexibility; constant course adjustments  Include access & global political mobilization in agenda  Work with anyone who can help

26. The AIDS vaccine situation today  Pipeline is more robust but clearly less than adequate (some increase in both depth & breadth)  Some industrial players coming back in with shareholder’s resources (Merck)  First vaccine efficacy testing completed (VaxGen)  Enhanced efforts by public sector institutions (NIH, EC, WRAIR)  New Players & models (VRC, IAVI, EDCTP, PAVE, CANVAC, AAVP, etc.)  Political leadership is clearly stronger (PM Vajpayee, President Kalam, President Kibaki, etc.) but not yet adequate in developed or developing countries

27. Mechanism Proven  7 Vaccine Development Partnerships  5 vaccines into the clinic in five years (5x5)  Clinical trials in 9 countries  Quality across all sites: network of accredited labs  Development of sustained capacity in the South  Prioritise and stop programmes on basis of data  Full participation of affected communities and DC’s  Developing countries can deliver excellent work  Strong support for AIDS vaccines from 8 OECD governments  Increased political leadership in North and South  All was done with small amounts of money 

28. Optimising strategies  Long-term commitment to a systematic problem-solving agenda u Redundancy of similar candidates needs to give way to cooperative selection of better candidates u Attack basic issues in vaccine research through cooperative approaches u Creative mechanisms linking basic research scientists with vaccine designers - Multidisciplinary involvement u Increase resource intensity to quickly get generally useful clinical data  Frame of reference in order to make resource allocation decisions (e.g. public health impact, absence of market, scientific complexity, availability of other effective preventive interventions): Priority Medicines report, Copenhagen Summit  Full involvement of developing countries

29. Implications  Effort has to be programmatic (e.g. Malaria Vaccine Initiative, International AIDS Vaccine Initiative)  Create mechanisms that facilitate global health R&D  If the rules don’t allow for it, change the rules  Willingness to pool resources and knowledge and stimulate global co-ordination (NIH, ANRS, MRC, DG Research, Global Vaccine Enterprise etc.)  IP should not be a barrier for vaccine R&D and delivery to developing countries  Industry willing to share technologies if roadmap for effective vaccine is designed  A vaccine that is not used is meaningless: think through access issues now!

30. Implications for Europe  Accept differentiation between solving a global health problem and strengthen European competitiveness  Accept the fact that PD PPP’s are adding value  Act accordingly - Create mechanism for translational research that also would be accessible to global PD PPP’s as well  Take responsibility in closing US $ 1,2 – 2.2 billion gap by 2007  The time is right now: Technology Platforms for Innovative Medicines and Chemistry; 7 th framework, EDCTP, 3% target  Create a better European infrastructure through structural funds (and not through funds for development cooperation)  Consortia and consensus  quality, evidence, effectiveness and efficiency  Make more money available: long term programmes

31. Preliminary Estimates 2002: Funding by Sector Estimated Total Spending: $540 – $570 million

32. The best time to plant a tree was twenty years ago. The next best time is today African saying

33. Clinical trials  Europe: UK, Switzerland, Belgium, Germany  SSA: Uganda, Kenya, South Africa, Zambia, Rwanda  India: Pune, Chennai  US: New York

34. Lab infrastructure  Human Core Lab: London (Imperial College)  Network of accredited labs (Kenya, Uganda, South Africa)  In construction: Zambia, Rwanda  In constructing: India (Pune, Chennai)

35. Benefits for private sector  Slides Mary

36. Innovative medicines and priority medicines  Pharma not interested in priority medicines areas such as u TB u Anti microberials u HIV/AIDS  Clearly relevant for Europe  Open plaformupto PD PPP’s