New Drugs for Neglected Diseases: The PDP / DNDi Model & Chagas Disease

1. New Drugs for Neglected Diseases:The PDP / DNDi Model & Chagas Disease IDEA-UAEM Workshop, April 2009 Jana Armstrong, Director DNDi North America

2. Neglected Disease Control Challenges Environmental factors: Populations live in poor, remote, sometimes politically unstable areas Health system capacity Inappropriate or nonexistent tools: Vector control & resistance No effective vaccines Invasive or no diagnostics Existing drugs toxic, difficult to administer, long course, expensive

3. Product Development Partnerships to Address R&D Gaps

4. The DNDi Example: founded in 2003 Primary Objective: To deliver 6 - 8 new treatments by 2014 for sleeping sickness, Chagas, leishmaniasis, & malaria & a robust pipeline for future needs Secondary Objectives: Use and strengthen existing capacity in endemic countries Raise awareness about the need to develop new drugs for neglected diseases and advocate for increased public responsibility

5. DNDi’s Disease Focus

6. Access – Capacity Strengthening - Advocacy Scope of Activities for DNDi 3 Core Diseases Sleeping sickness (HAT) Chagas disease Visceral leishmaniasis (VL) 3 Core Diseases + malaria: completed the 2 FDC + cutaneous leishmaniasis

7. Long- term projects Medium- term projects Short- term projects DNDi Portfolio-Building Model • New lead compounds • Existing compounds • New formulations (fixed dose combinations) • New indications of existing drugs • Completing registration dossier • Geographical extension

8. a robust pipeline DNDi R&D Projects – 2009 Outlook NECT Nifurtimox - Eflornithine Co-Administration (HAT) Fexinidazole (HAT) GSK (All) • 2 HAT LO Consort: • Scynexis • Pace Univ Buparvaquone (VL) Combination Therapy (VL in Asia) Kitasato Natural Substances(HAT) Amphotericin B Polymer (VL) Combination Therapy(VL in Africa) New formulation AmphoB (VL) - in preparation DUNDEE (VL) Paromomycin VL Consort: Advinus, CDRI ASMQ (Malaria) Fixed-Dose Artesunate/Mefloquine Eskitis Natural Products (HAT) 8 aminoquinolines (VL) - in preparation AmBisome Miltefosine – in preparation Exploratory IPK (VL) Chagas Consort: CDCO, Epichem, Murdoch Univ Combination Therapy (VL in Latin America) – in preparation ASAQ (Malaria) Fixed-Dose Artesunate/ Amodiaquine Exploratory Paediatric Benznidazole (Chagas) Screening: LSTMH, Swiss Tropical Institute, Antwerp University, Murdoch, UFOP, Fiocruz 6 to 8 new treatments Azoles (Chagas) Exploratory

9. 2004-2014 Estimated Expense: ~$400M Important role for private and public funding partners

10. Three Treatments Delivered in Five Years Strategic Partners 2007 sanofi-aventis (France) ASAQ (Malaria) Fixed-Dose Artesunate/ Amodiaquine • Easy to Use • Affordable • Field-Adapted • Non-Patented Farmanguinhos (Brazil) Cipla (India) 2008 ASMQ (Malaria) Fixed-Dose Artesunate/Mefloquine National Control Programs Doctors Without Borders (MSF) WHO 2009 NECT Nifurtimox - Eflornithine Co-Administration (HAT)

11. LEAP and HAT Platforms: Partnering Locally to Strengthen Capacity & Regional Disease Control Collaboration • Recruitment of patients for Clinical Trials • Training: GCP, GLP, ethics committees, DSMB • Health Facility Upgrades SUDAN: 2 sites Univ. of Khartoum Federal Ministry of Health MSF ETHIOPIA: 2 sites Addis Ababa Univ. Gondar Univ. DACA Ministry of Health TMRI, Sudan PNLTHA, DRC MoH-GoSS PNLTHA, RoC KENYA: 1 site KEMRI Ministry of Health MSF COCTU, Uganda + • UGANDA: 1 future site • Makarere Univ. • Ministry of Health DNDi ICCT, Angola + Partners

12. Public sector needed to promote innovation & sustainability for ND R&D -R&D Priority Setting -Enabling regulatory environment promoting rapid approval and delivery of new drugs -Access to knowledge - IP policies encouraging needs-driven R&D -Research capacity strengthening in disease endemic countries -Sustainable funding mechanisms

13. Chagas Disease: a silent killer • Endemic in 21 countries - Central and South America, & Mexico • Highest disease burden in Mexico, Brazil, Argentina & Bolivia • Parasitic disease transmitted by the triatoma / vichuca / “kissing bug” • 8 - 15 million infected individuals / 60 - 100 million at risk for infection • 41,000 new cases “reported” / year due to vector transmission • Estimated up to 70% cases go unreported • 3rd largest disease burden in Latin America (after malaria & schistosomiasis) • 3 to 5 million with chronic cardiac and/or digestive complications • At least 14,000 deaths per year • Estimated 667,000 DALYs / year

14. Chagas Migratory Flows PAHO/WHO, 2007

15. Chagas’ Disease Progression Acute Phase – Indeterminate - Chronic • Acute: if treated, cure rate 90%, but often not diagnosed • Indeterminate: 10-20 years, no symptoms, >40% progress to chronic, clinically evident disease • Chronic: Most commonly leads to progressive heart enlargement and failure, no treatment

16. Barriers to Chagas Disease control • Affects poor rural populations with no voice and varying access to diagnosis, care or treatment • Emphasis has been on vector control, not patient treatment • Chagas disease well known in rural areas of endemic countries but stigma attached to infection status and perception that nothing can be done leading to underreporting • Though drugs are donated, drugs not readily available • Asymptomatic and diagnosis difficult after acute stage • Difficulty in test of cure complicates clinical research • No political will so almost no financing for R&D – not even Gates funds Chagas R&D

17. DNDi R&D Chagas Projects – 2009 Outlook 2014 Objectives: 1 New Drug 1 Pediatric Formulation A Robust Pipeline GSK (All) Chagas Consort: CDCO, Epichem, Murdoch Univ Back up Azoles (Chagas) Paediatric Benznidazole (Chagas) Exploratory Exploratory Azoles (Chagas) Exploratory

18. Long Term: Access to Chemical Diversity and Lead Optimization Chemroutes NITD SIMM CDRI Eskitis Univ Washington GSK IRD Epichem Scynexis Basilea Otsuka WEHI UCSF Institut Pasteur Korea Nycomed Altana Anacor Ranbaxy Boston Univ Evolva WRAIR Chagas Lead Optimisation Consortium CDCO, Epichem, Murdoch University

19. How Universities & UAEM Can Help • Identify Chagas & other NTD research programs – revive dormant projects or at least raise awareness to them • Adopt global access licensing/tech transfer principles • Economic evaluation of funding mechanisms • Develop strong links with disease endemic universities • Join / Promote 2009 Chagas Campaign to advocate for improved disease control and new tools