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

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

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

TB-HIV Pandemic

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

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

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

2000

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

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

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

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

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

Building the Pipeline

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

2002

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

2003

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

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

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 98-1-81 & 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

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

2004

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)

2005

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 www.tballiance.org October 2005

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

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

Where We Are Today

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

Strategic Evolution

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

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

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

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

External Landscape

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.”

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

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

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

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