Working Group on TB Drugs Developing A Faster Cure Maria C. Freire, Ph.D. Chair

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

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

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

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

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

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

? Mapping Exercise Basic Research Discovery Lead Identification & Optimization Preclinical Clinical Trials Regulatory Compounds Technology Platforms Capacity Building ?

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

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

Mapping Results to Date (by project)

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

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

Scaling Up R&D Activities

Case Studies

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.

PA-824 Development Schedule

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

Moxifloxacin

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

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

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. +

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!