1. Public/Private Partnerships in Global Health Initiatives
Gerald J. Siuta, Ph.D., CLP
Consultant, Business Development
New York University Global Health Alliance
New York City, NY
March 27, 2009

2. Global Tuberculosis Epidemic
One-third of the world’s population is infected with Mycobacterium tuberculosis (M.tb.)
2 billion people
8-9 million develop active disease annually
2 million deaths occur each year
1 person dies every 15 seconds
400,000 cases of MDR-TB each year
Leading cause of death in HIV-positive people
12 Million people are TB/HIV co-infected
TB’s economic toll: $16 billion a year

3. Current TB Drug Therapy
Active TB
Standard therapy – 4 drugs (isoniazid, rifampin, pyrazinamide & ethambutol) for 2 months, followed by isoniazid and rifampin for 4 months
Latent TB
Standard therapy – isoniazid for 9 months
Multi-Drug Resistant TB (MDR-TB)
Individualized, prolonged therapy, few available drugs, poorly tolerated and difficult to administer
TB/HIV Co-Infection
Treatment as in active TB, but drug interactions with antiretroviral agents make simultaneous therapy difficult
Extensively Drug Resistant TB (XDR-TB)
No treatment available

4. The Need for New TB Drugs
Complex 6-9 months treatment with a drug combination regimen
No new anti-TB drug in over 40 years
TB/HIV co-infections fueling each other
MDR-TB is on the rise
Unattractive market for private sector
No capitalization of public sector research

5. History of the TB Alliance
Cape Town Declaration – February 2000
Hosts: Rockefeller Foundation and the Medical Research Council of South Africa
Over 120 organizations (health, science, philanthropy and private industry)
Results
Support goals of Stop TB Initiative
Create Scientific Blueprint
Develop Pharmacoeconomic Analysis
Build a Global Alliance for
TB Drug Development

6. The TB Alliance
Independent, international Product Development Partnership founded in October 2000
Non-profit organization
Headquarters in New York City
Offices in Brussels and Cape Town
Entrepreneurial, virtual R&D approach
Out-source R&D to public and private partners
Pro-active fundraising
Over US $200 million raised
Support ~ 200 FTE worldwide and 38 FTE in-house

7. Our Mission
Develop an entirely new therapeutic regimen that will shorten or simplify the treatment of tuberculosis
Coordinate and act as catalyst for global TB drug development activities
Ensure Affordability, Adoption and Access (AAA Strategy)

8. AAA Strategy Affordability Adoption Access
Appropriate pricing in developing countries
Adoption
Ensure that new drugs are incorporated into existing treatment programs
Access
Procurement and distribution to those patients who need them most

9. Our Vision
FDCs
10 Days
2 Months
6 Months

10. Profile of a New TB Drug Shorten treatment to less than 2 months
Novel mechanism of action (MDR/XDR-TB)
Orally active
Once daily or intermittent therapy
Compatible with HIV treatment
Low cost of goods

11. Financial Support Bill and Melinda Gates Foundation
Rockefeller Foundation
Netherlands Ministry for Development Cooperation
United States Agency for International Development (USAID)
Governments of Great Britain and Ireland

12. Types of Deals In-Licensing IP Assignment Sponsored R&D
Collaborative R&D
Freedom to Operate
Clinical Trials

13. Industrial Partners Bayer HealthCare Chiron/Novartis GlaxoSmithKline
Novartis Institute for Tropical Diseases
sanofi-aventis

14. Academic Partners Infectious Disease Research Institute
Institute of Materia Medica (China)
Johns Hopkins University
Korea Research Institute of Chemical Technology/Yonsei University (South Korea)
Rutgers, The State University of New Jersey
Texas A&M University
University of Auckland (New Zealand)
University of Illinois at Chicago
University of Pennsylvania

15. TB Alliance Portfolio TB ALLIANCE PROGRAMS DISCOVERY
CLINICAL DEVELOPMENT
Lead Identification
Lead Optimization
Preclinical
Phase I
Phase II
Phase III
Moxifloxacin
PA-824
Quinolone TBK-613
Nitroimidazoles
Pleuromutilins
Mycobacterial Gyrase Inhibitors
Multifunctional Molecules
InhA Inhibitors
Riminophenazines
Phenotypic Screening
Focused Screening
Malate Synthase Inhibitors
Protease Inhibitors
Energy Metabolism Inhibitors
RNA Polymerase Inhibitors
NITD Portfolio 15

16. Bayer HealthCare Moxifloxacin Fluoroquinolone antibiotic Orally active
Once-a-day dosage
Approved in 104 countries for the treatment of bacterial respiratory and skin infections

17. Bayer HealthCare Moxifloxacin Fluoroquinolone antibiotic Orally active
Once-a-day dosage
Approved in 104 countries for the treatment of bacterial respiratory and skin infections

18. Moxifloxacin for TB
Novel mechanism of action: kills M.tb. by inhibition of DNA gyrase
In vivo studies showed moxifloxacin reduced treatment time by two months when substituted for isoniazid
Safe to use with antiretroviral agents since it is not metabolized by the cytochrome P-450 enzyme system

19. The Partnership
Clinically assess the efficacy and safety of moxifloxacin as a front-line agent for the treatment of TB
If clinical trials are successful, register moxifloxacin for a TB indication
Committed to making the product affordable and accessible to patients in the developing world

20. Moxifloxacin Clinical Trials
Evaluate whether substitution of moxifloxacin for one of the standard TB drugs (isoniazid or ethambutol) eliminates TB infection faster than current therapy
Trials to be run in Brazil, Canada, South Africa, Spain, Tanzania, Uganda, the United States and Zambia
More than 3,000 TB patients to be enrolled

21. Bayer Commitments Donate moxifloxacin for each clinical trial site
Cover costs of regulatory filings
Provide moxifloxacin at an affordable price for patients with TB in the developing world

22. TB Alliance Commitments
Coordinate and help cover the costs of the clinical trials
Ensure coordination of information and results towards the goal of registration
Leverage substantial support from:
U.S. Centers for Disease Control and Prevention (CDC)
Orphan Products Development Center of the U.S. Food & Drug Administration
European and Developing Countries Clinical Trials Partnership (EDCTP)

23. Chiron/Novartis PA-824 – A novel nitroimidazole
Discovered by Pathogenesis, Inc.
Distinct mechanism of action
Potent activity against both active and slow growing M.tb.
Possesses both bactericidal and sterilizing activity

24. Chiron/Novartis
Worldwide exclusive license for the treatment of tuberculosis
Defined scientific milestones
Grant-back option
Manufacturing rights
No royalties in developing world

25. Korea Research Institute of Chemical Technology (KRICT)
Located in Daejeon, South Korea
Synthesized more than 600 quinolones, pyridones & quinolizines
In vitro and in vivo biological testing at the Yonsei University College of Medicine in Seoul, South Korea
One lead compound has been selected for further preclinical evaluation

26. University of Auckland
Synthesis of PA-824 analogs
Identified many new pharmacophores, several of which have demonstrated potent activity against TB
Optimization has led to nitroimidazole analogs that have in vitro activity greater than PA-824

27. GlaxoSmithKline
Joint drug discovery program at GSK’s Diseases of the Developing World facility in Tres Cantos, Spain
Five individual projects:
Mycobacterial gyrase inhibitors
InhA inhibitors
Malate synthase inhibitors
Pleuromutilins
Focused screening

28. Institute of Materia Medica
Joint research partnership for the design, synthesis and evaluation of a class of compounds known as riminophenazines
Class was discovered in the 1950s
The collaboration will utilize IMM's expertise and integrated capabilities in chemistry, pharmacology and manufacture

29. Global Alliance for TB
Drug Development