1. Collaborating with Public-Private Partnerships: The Global Alliance for TB Drug Development
Gerald J. Siuta, Ph.D.
Consultant, Business Development
5th Anti-Infectives Partnering & Deal-Making Summit
Philadelphia, PA
March 7, 2008

2. What is a Public-Private Partnership?
An organization that pursues a social mission by employing the best practices of the private sector and drawing upon resources from the public and private realms

4. Types of PPPs Basic Knowledge/Research
SNP Consortium
Improvement of Access to Health Products
International Trachoma Initiate
Global Coordinating/Funding Mechanisms
Global Fund to Fight AIDS, Tuberculosis and Malaria
Health Services Strengthening
Global Campaign for Microbicides
Public Education and Advocacy
Corporate Council on Africa
Regulation, Quality and Standards
Anti-Counterfeit Drug Initiative
Product Development Partnership (PDP)
Global Alliance for TB Drug Development

5. PDP Operations Provide specific disease expertise
Fill development gaps
Have purchasing power – US$1B for TB alone
Unique deals, not charity projects
Undertake clinical development
Build extensive networks for market access in developing countries
Provide credibility with advocates, NGOs and activists

6. How PDPs Work

7. Who are PDPs?

8. Case Study:
TUBERCULOSIS

9. 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

10. 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

11. 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

12. 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

13. 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 35 FTE in-house

14. 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)

15. 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

16. Our Vision
FDCs
10 Days
2 Months
6 Months

17. 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

18. 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

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

20. TB Alliance Portfolio TB ALLIANCE PROGRAMS DISCOVERY
CLINICAL DEVELOPMENT
Lead Identification
Lead Optimization
Preclinical
Phase I
Phase II
Phase III
Moxifloxacin
PA-824
Quinolones
Nitroimidazoles
Pleuromutilins
Mycobacterial Gyrase Inhibitors
InhA Inhibitors
Multifunctional Molecules
Riminophenazines
GSK Focused Screening
Phenotypic Screening
Malate Synthase Inhibitors
STRATEGIC INITIATIVES
Evaluation of New Drug Combinations
Fast-tracking the testing of new regimens
Mouse Model of Tuberculosis
Optimizing a preclinical research model
Product Profile Analysis
Defining the value proposition of new regimens
Identification of Biomarkers
Identifying new determinants of successful treatment
Market Analysis
Identifying market dynamics that affect availability
Regulatory Mapping
Understanding pathways in high-burden countries
Clinical Trial Site Assessments
Identifying clinical research sites and targeting improvements
Regulatory Preparation Forums
Learning what is needed for registration

21. 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

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

23. Development of PA-824 Phase I clinical trials began June 3, 2005
Preclinical development completed in 3 years
Drug was well tolerated with no definitive dose-limiting adverse events
Phase II extended Early Bactericidal Activity (EBA) study has begun in Cape Town, South Africa

24. 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

25. 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
Pleuromutilins
Focused screening
Malate synthase inhibitors

26. GlaxoSmithKline Project oversight by Joint Steering Committee
TB Alliance helps to support 25 full-time scientists at GSK working exclusively on the TB drug program
GSK absorbs all remaining overhead costs
GSK contributes a matching number of staff
Any resulting medicines will be made affordable and accessible to those most in need

27. 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
Four lead compounds have been selected for further preclinical evaluation

28. Cumbre Pharmaceuticals
Joint program on the design, synthesis and optimization of multi-functional antibiotics
The TB Alliance has exclusive rights to these compounds for the treatment of tuberculosis and other neglected diseases
Cumbre retains rights to pursue the compounds for use in other infectious disease areas

29. 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

30. The TB Alliance-Bayer
Moxifloxacin Deal

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

32. 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

33. October 18, 2005
TB Alliance and Bayer HealthCare announced a partnership to coordinate a global clinical trial program to study the potential of moxifloxacin to shorten the standard six-month treatment of TB

34. 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

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

36. 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

37. 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)

38. Global Alliance for TB
Drug Development