Working Group on TB Drugs

1. Working Groupon TB Drugs Developing A Faster Cure Maria C. Freire, Ph.D. Chair

2. Working Group Coordination Treatment Today Treatment Tomorrow DOTS-Plus MDR-TB New TB Vaccines HIV/TB DOTS Expansion New TB Drugs New TB Diagnostics

3. Mission To deliver faster and affordable TB medicines that will be the cornerstone of tomorrow’s TB control.

4. WG Membership ABPI • ALA •Alkem • Astrazeneca • ATS •Aventis •Bayer • Case Western • CDC• Denver Health & Hospitals • DFID-UK • Faculte de Medicine Pitie-Salpetriere • FDA • Gates Foundation • GATB • GlaxoSmithKline • Global Forum for Health Research • Hikal Ltd. • EU Research Directorate • IUATLD • JATA • Johns Hopkins • KNCV • Kyoto Pharmaceutical Univ. • Lupin Ltd. • MSF • MRC • NIH • NIPER • Novartis • Partners in Health • Pfizer • Rockefeller Foundation • RTI • TDR • Sequella • St. George’s Hospital Medical School • Stop TB • Tuberculosis Research Center-Chennai • University of Natal • University of Rio de Janeiro • USAID • Wanchai Chest Clinic • WHO • The World Bank

5. New Drug Profile • Simplify or shorten TB treatment to 2 months or less • Be effective against MDR-TB • Shorten/improve latent TB treatment • Easily adopted in the field

6. Drug Development Pipeline Gap Phase III Basic Research Discovery Pre- Clinical Phase II Registration & Post Clinical Phase I

7. Technology Mapping • Goal: • Assess TB drug development landscape within WG • Process: • Formed Subcommittee of Core Group • Surveyed 60 WG Members, 25 responded • Results: • Discussion of preliminary data • Evaluation of information

8. Mapping Exercise ?

9. Mapping Results to Date By Project

10. Mapping Results to Date By Project

11. Mapping Results to Date (by project)

12. Lead Identification Lead Optimization Pre-Clinical Clinical WG Portfolio Data PA-824 Analogs PA824 Moxifloxacin Pyridones and Quinolizines Thiolactomycin LL-3858 (Pyrroles) Rifapentine Ascididemin Compounds KRQ 10018 Rifabutin Third Generation Macrolides PA 20013 Compounds Capreomycin Ethambutol Analogs Gatifloxacin MJH 98-I-81 & Analogs Levofloxacin Rifalazil Analogs Linezolid Anti-Persisters Ofloxacin Combination Project Non-profit Project Industry Project TB Alliance Project

13. Late Discovery Pre- clinical Phase I Phase II Phase III Portfolio Management ----------------------------Clinical Trials-------------- Lead identification and optimization Pre-clinical Development Contracts and IP Management for Equitable Access Streamline Development Ensure Prompt Registration & Field Transfer Accelerate Discovery

14. Scaling Up R&D Activities

15. Case Studies

16. PA-824 “[This] deal tells me … that biotech leaders, international health officials and philanthropic groups are trying to create mechanisms to address needs that would otherwise fall through the cracks. I’m keeping my fingers crossed, both for the TB drug and the larger experiment in non-profit drug development.” Tom Abate, Biotech columnist, San Francisco Chronicle.

17. PA-824 Development Schedule

18. Brazil Drug Development Outsourcing Network Under Evaluation: Peru Russia India South Africa Existing Sites

19. Moxifloxacin

20. 1st Results from MXF Studies Moxifloxacin MurineModel Results of log10 CFU counts from lung homogenates. (Jacques Grosset & William Bishai - JHU)

21. Clinical Trials Moxifloxacin Phase II • Johns Hopkins U & Brazil (FDA Orphan Drug Office) • CDC TBTC Study 27 • TRC Chennai

22. AAA strategy: Affordability, adoption, access. Strategic IPR Provisions Ensure endemic country participation early on Build-in provisions for technology transfer and support for production in developing countries. + + Special Considerations

23. Conclusions • First TB pipeline in 40 years • World-wide participation in WG activities • New TB Drugs will revolutionize DOTS • Must ensure sustainability • The time to act is NOW!