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

Contents Product development partnership (PDP) model Example of a PDP: Medicines for Malaria Venture (MMV)

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. 3

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

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

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 G-FINDER report

Treatments: Activities of PDPs 104 biopharmaceutical candidates in development 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 59 Pre Clinical 15 Phase I 12 Phase II 10 Phase III 2 Registration 6 Launched Drugs Vaccines Microbicides # candidates 10% 12% 14% 57% 6% 2% Slides source from:

Diagnostics and vector control: Activities of PDPs 39 candidates 7Feasibility 7 Test DevelopmentTest DevelopmentTest DevelopmentTest Development 6Evaluation 1 Demonstration 6 Country AdoptionCountry AdoptionCountry AdoptionCountry Adoption CD4 FIND IDRI 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 4% 22% 26% 22% Early Stage In DevelopmentIn DevelopmentIn DevelopmentIn Development IVCC # candidates DiagnosticsVector control 26% Slides source from: &

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 Swiss Foundation based 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

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. 10

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 11

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 12

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 13

Composition of the MMV portfolio 2011 RegistrationPreclinical ResearchTranslationalDevelopment Lead OptPhase IIaPhase ILead GenPhase IVPhase IIb/III Novartis miniportfolio Novartis 2 Project MK 4815 (Merck) IV artesunate Guilin DHA-Piperaquine s igma-tau Coartem®-D Novartis GSK miniportfolio Broad/Genzyme miniportfolio Antimalarials St Jude/Rutgers Other Projects 12 Projects sanofi aventis Orthologue screen Kinases Monash Pfizer Screening GSK 2 Project NITD609 Novartis OZ 439 (Monash/UNMC/ STI) AZCQ Pfizer Pyramax® Shin Poong/University of Iowa ASAQ Winthrop sanofi aventis/DNDi Aminoindole Broad/Genzyme Aminopyridine UCT Quinolones USF/ VAMC Pyrazoles Drexel AstraZeneca Screening GNF156 Novartis DHODH UTSW/UW/Monash AN3661 Anacor Tafenoquine GSK

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

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 …..