1. Working Group on 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
Basic
Research
Discovery
Pre-
Clinical
Phase
III
Phase I
Phase II
Registration
& Post
Clinical

7. Technology Mapping Goal: Process: Results:
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 Basic Research Discovery Lead Identification &
Optimization
Preclinical
Clinical
Trials
Regulatory
Compounds
Technology
Platforms
Capacity
Building ?

9. Mapping Results to Date
By Project
Basic
Research
Discovery
Lead Identification &
Optimization
Preclinical
Clinical
Trials
Regulatory
Compounds
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Technology
Platforms ●● ●
Capacity
Building

10. Mapping Results to Date
By Project
Basic
Research
Discovery
Lead Identification &
Optimization
Preclinical
Clinical
Trials
Regulatory
Compounds
●●●●
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●●●●●●
●●●●●
Technology
Platforms ●● ●
Capacity
Building

11. Mapping Results to Date (by project)

12. WG Portfolio Data Compounds Lead Identification Optimization
Pre-Clinical
Clinical
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
Non-profit Project
TB Alliance Project
Industry Project
Combination Project

13. Portfolio Management Contracts and IP Management for Equitable Access
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. Tom Abate, Biotech columnist,
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. Drug Development Outsourcing Network
Under Evaluation:
Peru
Russia
India
South Africa
Existing Sites
Brazil

19. Moxifloxacin

20. 1st Results from MXF Studies
Moxifloxacin Murine Model 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. Special Considerations
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. +

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!