Financing and R&D for neglected diseases Role of Product Development Partnerships

1. Financing and R&D for neglected diseases Role of Product Development Partnerships First meeting of Consultative Expert Working Group on Research and Development: Financing and Coordination – Open Forum 6 April 2011

2. Contents Product developmentpartnership (PDP) model Example of a PDP: Medicines for Malaria Venture (MMV)

3. PDP model Leverages public and philanthropic funds Engages the pharmaceutical industry and academic research institutions Undertaking R&D for diseases of the developing world that they would normally be unable or unwilling to pursue independently, without additional incentives.

4. PDPs leverage the strengths of global partners to develop new tools for neglected diseases Public sector (early research, funding…) Private sector (compound libraries, facilities, expertise …) PDPs (portfolio mngt, scientific due diligence, create links across academia /industry; incentivize …) Philanthropy (funding, fund raising ….)

5. The PDP model is vital to the R&D process for neglected diseases Access to best science, high tech facilities, skills compound libraries from Academia, Pharma and Biotech e.g. 6 million compounds screened for malaria and 25,000 new starting points identified Innovative and cost-effective Portfolio management allows flexibility to reallocate resources Apply rigorous industry style practices to progress projects through pipeline Shares the risk of R&D investment Uses funding to leverage further private sector assets, creating a virtuous circle Champions role in approaching unaddressed public health problems Trusted “broker” working across sectors and within countries

6. PDPs received less than 17% of global funding for neglected diseases in 2009 Funding to PDPs in 2009 was $530.0m This represented 16.6% of global funding, 22.5% of global grant funding for neglected diseases 2010 G-FINDER report

7. 8 Treatments: Activities of PDPs104 biopharmaceutical candidates in development 59 57% Pre Clinical 15 14% Phase I 12 12% Phase II 10% 10 Phase III 2 2% Drugs Registration Vaccines 6 6% Microbicides Launched # candidates Notes: Includes products not funded by Gates Foundation. Biopharmaceutical candidates in development Include: IAVI, IPM, IVI, GATB, Aeras, MMV, MVI, MVP, PVS, DNDi, iOWH, PDVI, HHVI. Source: PDPs Slides source from:

8. 8 Diagnostics and vector control: Activities of PDPs39 candidates Diagnostics Vector control Early Stage Feasibility 7 26% IVCC Test Development In Development 7 26% Evaluation 6 22% CD4 Demonstration 1 4% # candidates FIND Country Adoption 22% IDRI 6 Notes: Includes products not funded by Gates Foundation. Biopharmaceutical candidates in development Include: IAVI, IPM, IVI, GATB, Aeras, MMV, MVI, MVP, PVS, DNDi, iOWH, PDVI, HHVI. Source: PDPs & Slides source from:

9. Medicines for Malaria Venture: PDP to discover, develop and deliver effective & affordable drugs • Established in 1999 by WHO, World Bank, Governments, the Pharma Industry; subsequent funding from the Gates Foundation • SwissFoundationbased in Geneva • Largest ever antimalarial drug portfolio • Launched 1 product (with Novartis); two under regulatory review by European Medicines Agency (with sigma-tau and Shin Poong) • Supported prequalification of IV Artesunate for severe malaria (Guilin) • Partners in ca. 130 countries

10. Medicines for Malaria Venture – Our Mission MMV’s mission is to reduce the burden of malaria in disease-endemic countries by discovering, developing and facilitating delivery of new, effective and affordable anti-malaria drugs.

11. Managing the MMV portfolio R&D priorities and Target Product Profiles evaluated and agreed by Expert Scientific Advisory Committee (ESAC) and published on MMV website Call for proposals published annually Assessment of proposals by MMV Science Team and ESAC Grants awarded Projects managed on a daily basis in collaboration with MMV scientific expert and assessed annually by ESAC

12. MMV Governance structures MMV Board of Directors The highest policy and decision-making body of MMV which ensures that MMV’s objectives are efficiently executed by the management MMV North America Inc. Board Supports MMV’s Corporate Development activities in the USA Expert Scientific Advisory Committee (ESAC) Helps identify the best projects worthy of inclusion in the MMV portfolio and continues to monitor progress through an annual review of all projects Access and Delivery Advisory Committee (ADAC) Advises MMV on its global access activities to ensure timely and effective delivery of new antimalarial drugs in malaria endemic countries Global Safety Board (GSB) The Global Safety Board ensures adherence to scientific and ethical principles

13. MMV global priorities Malaria Increase the range of affordable quality ACTs to reduce morbidity and mortality Approval of quality treatment for severe malaria Children Development of age-appropriate formulations to safely and effectively dose the youngest patients Women and pregnancy Intermittent Preventative Treatment during Pregnancy Drug-drug interaction studies to support safe use with oral contraceptives Resistance New drugs with better pharmacokinetic and safety profiles and activity against artemisinin-resistant parasites Eradication: Transmission, relapse, long term protection

14. Composition of the MMV portfolio 2011 Research Translational Development Lead Gen Lead Opt Preclinical Phase I Phase IIa Phase IIb/III Registration Phase IV NITD609 Novartis Novartis miniportfolio Novartis 2 Project MK 4815 (Merck) OZ 439 (Monash/UNMC/ STI) AZCQ Pfizer DHA-Piperaquine sigma-tau Coartem®-D Novartis Tafenoquine GSK GSK miniportfolio GSK 2 Project GNF156 Novartis Pyramax® Shin Poong/University of Iowa ASAQ Winthrop sanofi aventis/DNDi IV artesunate Guilin Broad/Genzyme miniportfolio Aminoindole Broad/Genzyme AN3661 Anacor Pfizer Screening Aminopyridine UCT sanofi aventis Orthologue screen Pyrazoles Drexel AstraZeneca Screening Quinolones USF/ VAMC DHODH UTSW/UW/Monash Kinases Monash Antimalarials St Jude/Rutgers Other Projects 12 Projects

15. MMV Access and delivery R&D Scale-up Acceptance Outcome Pricing (contractual) Distribution Pharmacovigilance SRA1 Registration Country of origin WHO prequalification National registration Policy Essential Medicines List WHO treatment guidelines(scientific) Local guidelines / national policy 1. Stringent Regulatory Authority

16. Results from MMV partnerships • 55 million courses of paediatric Coartem distributed in Africa (MMV/Novartis) • IV Artesunate WHO pre-qualified and registered in 23 countries through (MMV/Guilin) • 2 new ACTs under regulatory review; paediatric formulations in advanced development (MMV/sigma-tau; MMV/Shin Poong) • Studies ongoing to reduce burden of malaria in pregnant women (MMV/Pfizer) • Programmes underway to improve understanding of malaria market dynamics (MMV/IMS/Vodaphone and Vodacom/Novartis) • Portfolio of fifty projects including potential single-dose cure, drugs with activity against artemisinin-resistant parasites, transmission blocking, relapse and long-acting drugs Partners include R&D-based Pharma, Generic manufacturers, academia, non-pharmaceuticals corporations, government …..