1. © IFPMA 2009 IFPMA to WHO EWG 12 Jan 09 1 Alicia D. Greenidge, Director General, IFPMA WHO Expert Working Group, Geneva, 12 Jan 2009 IFPMA Presentation to WHO Expert Working Group on Funding R&D for Diseases of the Developing World (DDW)

2. © IFPMA 2009 IFPMA to WHO EWG 12 Jan 09 2 R&D Industry Generic Industry Manufacture R&D Industry Product Development Partnerships (PDPs) Research & Development GovernmentsFoundations Access (incl. Delivery) Tackling DDWs: a Combined Effort… Academia Government Agencies R&D Industry Basic Research … to benefit patients in developing countries

3. © IFPMA 2009 IFPMA to WHO EWG 12 Jan 09 3 Industry is Committing Resources to DDW R&D through multiple mechanisms… Industry Dedicated DDW R&D Centers Independent Efforts Partnerships (Current industry involvement & partnerships - illustrative only - not comprehensive)

4. © IFPMA 2009 IFPMA to WHO EWG 12 Jan 09 4 R&D for a New Medicine: 10+ years, $1 bn+ Sources: Drug Discovery and Development: Understanding the R&D Process, www.innovation.org; CBO, Research and Development in the Pharmaceutical Industry, 2006 (1) incl. cost of capital – from The price of innovation: new estimates of drug development costs, DiMasi et al, Tufts Center for the Study of Drug Development, 2002 Indefinite Discovery Preclinical Clinical Trials Regulatory Review Scale-Up to Manufacture Post-Marketing Surveillance 1 Approved New Medicine 0.5 – 2 Years 6 – 7 Years 3 – 6 Years Number Of Patients / Subjects Phase I PhaseII Phase III 5 250 ~ 5,000 – 10,000 Compounds Pre-Discovery 20 – 100100 – 5001,000 – 5,000 IND Submitted NDA Submitted … a big challenge for addressing both developed and developing world diseases $335 million (1) $467 million (1)

5. © IFPMA 2009 IFPMA to WHO EWG 12 Jan 09 5 Industry R&D for DDW is Growing Number of Active R&D Projects Sources: 2005 - Moran et Al New Landscape… 2006, 2007, 2008 – IFPMA Status Reports # R&D Projects by IFPMA Companies, with Product Development Partnerships or alone 1 project = 1 compound in development OR 1 screening program for 1 disease TDR 10 Priority Diseases - Chagas - Dengue - Human African Trypanosomiasis - Leishmaniasis - Leprosy - Lymphatic Filariasis - Malaria - Onchocerciasis - Schistosomiasis - Tuberculosis Medicine R&D projects Vaccine R&D projects

6. © IFPMA 2009 IFPMA to WHO EWG 12 Jan 09 6 Industry DDW R&D is Increasingly Collaborative Sources: 2005 - Moran et Al New Landscape… 2006, 2007, 2008 – IFPMA Status Reports Companies working alone Companies working with PDPs # Medicine & Vaccine R&D Projects by IFPMA Companies, with PDPs or alone 32 49 58 67

7. © IFPMA 2009 IFPMA to WHO EWG 12 Jan 09 7 Current Industry DDW R&D is Mostly Early Stage Preclinical 39 projects Clinical 23 projects Registration 5 projects TOTAL (2008) 67 projects Non-industry R&D for DDW is also predominantly preclinical (or earlier)

8. © IFPMA 2009 IFPMA to WHO EWG 12 Jan 09 8 Factors for Increased DDW R&D Large Scale Donor Funding for Access Product Development Partnerships Increased Not-for-Profit R&D Work

9. © IFPMA 2009 IFPMA to WHO EWG 12 Jan 09 9 Central Role of PDPs in DDW R&D Independent PDP-driven R&D Bringing partners together over the last decade… World Bank Rockefeller Bill & Melinda Gates Wellcome Trust USAID DFID PEPFAR PMI Grand Challenges CIDA Global Fund GAVI Doris Duke Clinton Foundation Carter Center Basic Research Organizations TB medicines2000 TB treatments1998 Hookworm vaccines2000 Rotavirus vaccines2003 Pneumonia vaccines2003 Malaria, rotavirus, JE, pneumococcal & meningitis vaccines 1977 Malaria vaccines1999 Malaria medicines2000 Dengue vaccines2003 VL, malaria, diarrhoea & STH medicines 2000 HAT, VL, Chagas & malaria medicines 2003 TB vaccines2003 FocusSincePDP Funders Product Development Partnerships R&D Execution (Funders, PDPs, Basic Research Organizations & Industry Players - illustrative only - not comprehensive) Industry players

10. © IFPMA 2009 IFPMA to WHO EWG 12 Jan 09 10 Some DDWs are More Neglected than Others (HAT = Human African Trypanosomiasis or Sleeping Sickness) Some More Neglected Diseases need R&D more urgently than others and should be prioritized 4 Approved Meds: ALL intravenous or intramuscular, 3 are v. old 0 Approved Meds 2 Approved Meds: 1) intravenous & side effects 2) v. expensive 2 Approved Meds: BOTH less effective against fatal late stage 1 Approved Med: Effective, large donation program. Resistance? 3 Approved Meds: Effective, large donation program 1 Approved Med: Effective, large donation program Source: 2008 IFPMA Status Report

11. © IFPMA 2009 IFPMA to WHO EWG 12 Jan 09 11 Current DDW R&D Funding will be Insufficient as Pipelines Advance Dalberg Study for IFPMA (2007) Total Funding for PDPs to 2007 = USD 0.5 billion Total Funding for PDPs to 2007 = USD 0.5 billion Est. funding to take current PDP pipelines to approval AND to augment inadequate pipelines for Most Neglected Diseases = USD 8.3 billion Est. funding to take current PDP pipelines to approval AND to augment inadequate pipelines for Most Neglected Diseases = USD 8.3 billion Dalberg Study for IFPMA (2007) Total Funding for PDPs to 2007 = USD 0.5 billion Total Funding for PDPs to 2007 = USD 0.5 billion Est. funding to take current PDP pipelines to approval AND to augment inadequate pipelines for Most Neglected Diseases = USD 8.3 billion Est. funding to take current PDP pipelines to approval AND to augment inadequate pipelines for Most Neglected Diseases = USD 8.3 billion Source: Dalberg for IFPMA

12. © IFPMA 2009 IFPMA to WHO EWG 12 Jan 09 12 DiseasesTreatments Stages of the R&D value chain Portfolio management Intermediaries & recipients Malaria & TB TDR list (1) - excluding those w/o PDPs TDR list - excluding Malaria and TB TDR list TDR list + 7 diseases from NTD list (2) Medicines Medicines + Diagnostics Medicines + diagnostics + vaccines Clinical trials focus – Malaria and TB (3) Discovery only – smaller diseases (3) All stages of the value chain – VL, Chagas, HAT (3 ) Full Portfolio management with Fund Partial Portfolio management with Fund Pre-selection of intermediaries / recipients All intermediaries - All recipients Firm Recommendation Initial recommendation Options Sustainable Funding Push financing – spot commitments Push financing – long term commitments Push financing – IFF mechanism Funding Prioritization Spreading Picking winners Impact based sequence Success based sequence Notes: (1) TDR: WHO Special Programme for Research and Training in Tropical Diseases (2) NTD: WHO Control of Neglected Tropical Disease programme (3) Clinical trials only for Malaria and TB, discovery only for other diseases without existing PDPs, all stages of the value chain for other diseases with existing PDPs Study Also Looked at Sustainable Funding Structure Source: Dalberg for IFPMA

13. © IFPMA 2009 IFPMA to WHO EWG 12 Jan 09 13 DDW R&D Trends that will Impact Financing Maturing Pipeline Maturing Pipeline More projects entering expensive later stages (clinical trials)More projects entering expensive later stages (clinical trials) Need to invest in trials infrastructure & regulatory frameworksNeed to invest in trials infrastructure & regulatory frameworks Regulatory delays can be significant (e.g. ~4 years in S. Africa)Regulatory delays can be significant (e.g. ~4 years in S. Africa) Some Avenues of Research Prove Fruitless Some Avenues of Research Prove Fruitless From Development, return to Basic Research (e.g. Dengue)From Development, return to Basic Research (e.g. Dengue) Implications for total funding and for overall timeframeImplications for total funding and for overall timeframe New Funding Sources / Incentives New Funding Sources / Incentives Advanced Market Commitment (AMC)Advanced Market Commitment (AMC) Priority Review Voucher (PRV)Priority Review Voucher (PRV) Recognition of Importance of DDW R&DRecognition of Importance of DDW R&D

14. © IFPMA 2009 IFPMA to WHO EWG 12 Jan 09 14 Enhanced Industry Contribution: Potential Next Steps Consult with WHO & other partners to prioritize DDW R&D needs Consult with WHO & other partners to prioritize DDW R&D needs Explore working with African Network for Drugs Discovery & Innovation (ANDI) Explore working with African Network for Drugs Discovery & Innovation (ANDI) IFPMA working on a Developing Country Young Researcher Award IFPMA working on a Developing Country Young Researcher Award IFPMA exploring ways to facilitate increased availability of industry resources IFPMA exploring ways to facilitate increased availability of industry resources IFPMA Members looking at additional activities in partnership with DNDi et al IFPMA Members looking at additional activities in partnership with DNDi et al Consulting on other possible collaborations Consulting on other possible collaborations Consult with WHO & other partners to prioritize DDW R&D needs Consult with WHO & other partners to prioritize DDW R&D needs Explore working with African Network for Drugs Discovery & Innovation (ANDI) Explore working with African Network for Drugs Discovery & Innovation (ANDI) IFPMA working on a Developing Country Young Researcher Award IFPMA working on a Developing Country Young Researcher Award IFPMA exploring ways to facilitate increased availability of industry resources IFPMA exploring ways to facilitate increased availability of industry resources IFPMA Members looking at additional activities in partnership with DNDi et al IFPMA Members looking at additional activities in partnership with DNDi et al Consulting on other possible collaborations Consulting on other possible collaborations

15. © IFPMA 2009 IFPMA to WHO EWG 12 Jan 09 15 ConclusionsConclusions DDW R&D has increased substantially DDW R&D has increased substantially Increased activity by Product Development PartnershipsIncreased activity by Product Development Partnerships Increased in-kind & not-for-profit contribution by industryIncreased in-kind & not-for-profit contribution by industry Current DDW R&D is mainly in less expensive earlier stages Current DDW R&D is mainly in less expensive earlier stages Funding requirements will increase as more projects move into clinical trialsFunding requirements will increase as more projects move into clinical trials Industry is working to help expand and improve current DDW effort Industry is working to help expand and improve current DDW effort Current volume of DDW R&D inadequate to deliver enough new medicines for all the most needy diseases Current volume of DDW R&D inadequate to deliver enough new medicines for all the most needy diseases Shortfall is significant – funding to date perhaps 10 % of what is neededShortfall is significant – funding to date perhaps 10 % of what is needed Additional funding critical to achieve adequate range of new medicines & vaccines for Most Neglected Diseases Additional funding critical to achieve adequate range of new medicines & vaccines for Most Neglected Diseases DDW R&D has increased substantially DDW R&D has increased substantially Increased activity by Product Development PartnershipsIncreased activity by Product Development Partnerships Increased in-kind & not-for-profit contribution by industryIncreased in-kind & not-for-profit contribution by industry Current DDW R&D is mainly in less expensive earlier stages Current DDW R&D is mainly in less expensive earlier stages Funding requirements will increase as more projects move into clinical trialsFunding requirements will increase as more projects move into clinical trials Industry is working to help expand and improve current DDW effort Industry is working to help expand and improve current DDW effort Current volume of DDW R&D inadequate to deliver enough new medicines for all the most needy diseases Current volume of DDW R&D inadequate to deliver enough new medicines for all the most needy diseases Shortfall is significant – funding to date perhaps 10 % of what is neededShortfall is significant – funding to date perhaps 10 % of what is needed Additional funding critical to achieve adequate range of new medicines & vaccines for Most Neglected Diseases Additional funding critical to achieve adequate range of new medicines & vaccines for Most Neglected Diseases

16. © IFPMA 2009 IFPMA to WHO EWG 12 Jan 09 16 R&D Industry Generic Industry Manufacture R&D Industry Product Development Partnerships (PDPs) Research & Development GovernmentsFoundations Access (incl. Delivery) Combined Effort Needed to Advance Existing & Future Pipeline for DDWs Academia Government Agencies R&D Industry Basic Research … to benefit patients in developing countries

17. © IFPMA 2009 IFPMA to WHO EWG 12 Jan 09 17 Thank You!