1. “State of the Alliance” The First 5 Years
CEO Presentation to
the Stakeholders’ Association
Paris
October 17, 2005

2. Overview
Our Mission in TB
5-year Review
Agenda for Today

3. Tuberculosis – a Global Epidemic
2 billion people infected with M. tb
12 million persons are TB/HIV co-infected
8 - 9 million new active TB cases/year
2 million people die/year
~ 400,000 cases of MDR-TB/year
Biggest killer of women of childbearing age

4. TB-HIV Pandemic

5. Current TB Drug Therapy
Latent TB
Standard therapy – INH for 9 months
Active TB
Standard therapy – 4 drugs for 2 months, 2 drugs for 4 months
MDR-TB
Prolonged therapy, few available drugs, poorly tolerated and difficult to administer
TB/HIV co-infection
Drug interactions with ARVs - simultaneous therapy difficult

6. Impact of Shorter TB Therapy
Expand TB control
Improve compliance and cure rates
Control MDR-TB
Stop major cause of death for HIV/AIDS
Improve efficiency of healthcare systems
Reduce burdens on patients and providers

7. Reversing R&D Gap for TB
Limited market overlooked by industry
Difficult
Science
Scientific
Advances
New incentives
New market data
Recognized Global Emergency
Underestimated Health Need

8. 2000

9. The TB Alliance International Public-Private Partnership
Independent, Not-for-Profit
Entrepreneurial, virtual R&D approach
Strong Board, Stakeholders Association and Scientific Advisory Committee

10. To provide new medicines for the improved treatment of TB
Vision
To provide new medicines
with equitable access
for the improved treatment of TB
New compound(s) registered by 2010

11. Mission
To accelerate discovery and/or development of new, cost-effective TB drugs that:
Shorten the duration of TB treatment
Improve the treatment of latent TB infection
Be effective against multi-drug resistant TB

12. The Global Alliance
Unwavering commitment to global public good with the modus operandi of an aggressive “biotech”
Guarantor of public investment to ensure equitable access
Transparency and accountability with best business practices
Enabling ventures with TB-endemic countries

13. Monitor and evaluate select projects
Assets
Extensive Scientific Expertise
Laser-sharp focus & follow-through
Active portfolio management along R&D chain
Stakeholders Association
Survey TB environment
Monitor and evaluate select projects
Actively manage
a portfolio of
projects

14. Building the
Pipeline

15. Approved Projects Status, September 15, 2001 Chiron Hearn KRICT
Due Diligence
Term Sheets/ Strategy
DEAL
Negotiations
Chiron
Hearn
KRICT
N. Zealand
JHU
IUATLD
TDR
Callahan
EBA
Re-structuring

16. 2002

17. Approved Projects * Status, October 6, 2002 Chiron Hearn KRICT
Due Diligence
Term Sheets/ Strategy
DEAL
Negotiations
Chiron *
Hearn
KRICT
N. Zealand
JHU
IUATLD
TDR
Callahan
EBA
Re-structuring

18. 2003

19. Compounds, Analogs and Derivatives
TB Alliance Portfolio 2003
Compounds, Analogs and Derivatives
Discovery
Preclinical
Clinical Testing
Nitroimidazole Analog
Nitroimidazole PA-824
(Chiron)
Moxifloxacin
(Bayer)
KRQ 10018
(KRICT/Yonsei University)
Nitroimidazole Analog
Pyrrole
(Lupin))
Carboxylates
(Wellesley College)
Quinolones
(KRICT/Yonsei University)
Macrolides
(University of Illinois at Chicago)
Screening and Target Identification
(AstraZeneca)
Contracted Program
Rifalazil Derivatives
(Activbiotics))
Program in discussion
Support to 3rd Parties

20. TB Alliance Platform Technologies 2003
Discovery
Preclinical
Clinical Testing
Mouse Model of TB
(Johns Hopkins University)
Regulatory Harmonization
Biomedical Info Resources / Database
(IntellectuAll Limited)
Clinical Trials Infrastructure
(IUATLD)**
Predictive Models for
Efficacy/ADME/Toxicity*
In portfolio
In discussion
KEY
* - Project in RFP stage
** - Project Complete

21. TB Alliance Portfolio Compounds Lead Identification Optimization
Pre-Clinical
Clinical
Platform
Investments
Compounds
Pyridones
and Quinolizines
KRQ 10018
(Quinolone)
PA 824
(Nitroimidazopyran)
Moxifloxacin
Ascididemin
Compounds
MJH & Analogs
(Isoniazid analogs)
Pyrroles
Third Generation
Macrolides
PA 647
(Nitroimidazopyran)
PA 822
(Nitroimidazopyran)
Rifalazil
Derivatives
Database of TB Compounds
and Related Technologies
Clinical Trials
Capacity Development
Murine Models
Regulatory Harmonization
Project in Portfolio
Under Contract Negotiations
Support to Third Parties

22. Outsourcing of PA 824 Preclinical Development
Canada
Baltimore, MD, USA
Bethesda, MD, USA
Columbia, MI, USA
Dottikon, Switzerland
Germantown, WI, USA
Palo Alto, CA, USA
Punjab, India
Rockville, MD, USA
Singapore, Singapore
Toronto, Canada,
USA
Switzerland
India
Singapore

23. 2004

24. Compounds, Analogs and Derivatives
TB Drug Portfolio 2004
Discovery
Preclinical
Clinical Testing
Compounds, Analogs and Derivatives
Nitroimidazole Analogs
(Novartis Institute for Tropical Diseases, NIAID)
Nitroimidazole PA-824
(Chiron)
Moxifloxacin
(Bayer Pharmaceutical, EDCTP)
Carboxylates
(Wellesley College)
Pyrrole LL-3858
(Lupin Limited)
Diarylquinoline R207910
(Johnson & Johnson)
Quinolones
(KRICT/Yonsei University)
Non-Fluorinated Quinolone
(Procter & Gamble)
Proprietary Compound
(Private Sector Company))
Macrolides
(University of Illinois at Chicago)
Enoyl ACP reductase inhibitors
(GlaxoSmithKline)
Isocitrate Lyase inhibitors
(GlaxoSmithKline)
Oxazolidinones
(GlaxoSmithKline)
Pleuromutilins
(GlaxoSmithKline)
TB Alliance portfolio
Methyltransferase inhibitors
(Anacor Pharmaceuticals)
TB Alliance in discussion/finalization stages
Screening and Target Identification
(AstraZeneca)

25. 2005

26. Compounds, Analogs and Derivatives
TB Alliance Portfolio 2005
Compounds, Analogs and Derivatives
Discovery
Preclinical
Clinical Testing
Nitroimidazole Analogs
(University of Auckland, Novartis Institute for Tropical Diseases,
National Institute of Allergy & Infectious Diseases)
Nitroimidazo-oxazole Backup Compound
(Otsuka Pharmaceutical)
Nitroimidazole PA-824
(Chiron)
Moxifloxacin
(Bayer)
Carboxylates & Pyrroles
(Wellesley College)
Nitroimidazo-oxazole OPC-67683
(Otsuka Pharmaceutical)
Quinolones
(KRICT/Yonsei University)
Macrolides
(University of Illinois at Chicago)
InhA inhibitors
(GlaxoSmithKline)
Isocitrate Lyase inhibitors
(GlaxoSmithKline)
Focused Screening
(GlaxoSmithKline)
Contracted Program
Program in discussion
Pleuromutilins
(GlaxoSmithKline)
Screening and Target Identification
(AstraZeneca)
Global Alliance for TB Drug Development October 2005

27. TB Alliance Platform Technologies 2005
Discovery
Preclinical
Clinical Testing
Mouse Model of TB
(Johns Hopkins University)
Biomedical Info Resources / Database
(IntellectuAll Limited)
Clinical Trials Infrastructure
(IUATLD)**
Platform Technologies
Regulatory Support
In portfolio
In discussion
KEY
Predictive Models for
Efficacy/ADME/Toxicity*
* - Project in RFP stage
** - Project Complete

28. Types of Deals & Agreements
Appropriate for Technology & Partner
Licensing
Sponsored Projects
Outsourcing/Contracts
Co-Development
Co-Investments
Partnerships

29. Where We Are Today

30. Then and Now Strategic Evolution 1 new drug Combinations
TB-only TB/HIV key priority
Affordability + Access, Adoption
External Landscape
Untested model Track Record
Seed funding Diverse Sources
Skepticism Support

31. Strategic Evolution

32. Shorten: 6 months to 2-3 months
Near-term Vision
Shorten: 6 months to 2-3 months
then
Simplify: daily to weekly
130 doses
10 doses

33. Strategic Shift
Advancing novel COMBINATIONS rather than single drugs through the drug development pipeline.

34. Long term Goal – Active Disease
<10 days of treatment
(Recognition of difficulties without advances in understanding the biology of “persistence”)

35. Affordability + Adoption + Access
Lowering cots while ensuring quality
Leverage/access IP rights
Adoption
Orally available, easy to use, compatible with ARVs
Leveraging WHO treatment protocol for TB
Access
Procurement & distribution – Stop TB, WHO, GDF
Funding via new mechanisms, and Global Fund to Fight AIDS, TB, Malaria

36. External Landscape

37. Public Endorsement: G8 on PPPs
“Building on the valuable G8 Global HIV/AIDS vaccine enterprise, increasing direct investment and taking forward work on market incentives, as a complement to basic research, through such mechanisms as Public Private Partnerships to encourage the development of vaccines, microbicides and drugs for AIDS, malaria, tuberculosis and other neglected diseases.”

38. Partners & Collaborators
Johns Hopkins U
US CDC
Research Triangle Institute
FDA Orphan Drug
EDCTP
FioCruz, Brazil
ICMR, India
MOH, Peru
Abbott
Bayer AG
Chiron
GlaxoSmithKline
Novartis
NIH/NIAID
KRICT
U. Illinois-Chicago

39. New Stakeholders Philippines Coalition Against Tuberculosis
National Institute of Pharmaceutical Education & Research, India
Japanese Research Institute of Tuberculosis
RESULTS
TB Alert
Global Fund to Fight AIDS, TB, Malaria

40. What’s Ahead Portfolio Growth and Sustainability
Aligning Resources to Need
Preparing for Adoption – Re-tooling

41. Agenda for Today Policy Context & Strategy R&D Presentations
TB Alliance Program
PPP Track Record
R&D Presentations
Substitution to Revolution
Programs with GSK
Clinical Program with Moxifloxacin
Discussion for 2006