The Global Alliance for TB Drug Development Gerald J. Siuta, Ph.D., CLP

1. The Global Alliance for TB Drug Development Gerald J. Siuta, Ph.D., CLP Consultant, Business Development Global Alliance for TB Drug Development Biotechnology Industry Organization International Convention Chicago, IL May 4, 2010

2. 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 Global Tuberculosis Epidemic TB’s economic toll: $16 billion a year

3. 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 Current TB Drug Therapy

4. Complex 6-9 months treatment with a 4 drug combination regimen No new anti-TB drug in over 50 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 The Need for New TB Drugs

5. 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 History of the TB Alliance Build a Global Alliance for TB Drug Development

6. 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 50 FTE in-house The TB Alliance

7. 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) Our Mission

8. Affordability 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 AAA Strategy

9. FDCs Our Vision 10 Days 2 Months 6 Months

10. 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 Profile of a New TB Drug

11. 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 Financial Support

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

13. TB Alliance Portfolio TB ALLIANCE PROGRAMS DISCOVERY CLINICALDEVELOPMENT Lead Identification Lead Optimization Preclinical Phase I Phase II Phase III Moxifloxacin TMC-207 PA-824 Nitroimidazoles Mycobact. Gyrase Inhibitors Riminophenazines InhA Inhibitors Diarylquinoline Phenotypic Screening Tryptanthrins LeuRS Inhibitors GyrB Inhibitors Whole-Cell Screening Malate Synthase Inhibitors Menaquinone Syn Inhibitors Natural Products RNA Polymerase Inhibitors Energy Metabolism Inhibitors Protease Inhibitors Topoisomerase I Inhibitors NITD Portfolio

14. Chiron Corporation/Novartis Bayer Healthcare AG Tibotec (Subsidiary of Johnson & Johnson) GlaxoSmithKline Anacor Pharmaceuticals Novartis Institute for Tropical Diseases AstraZeneca Industrial Partners

15. New York Medical College Rutgers University Colorado State University Institute of Microbiology (China) Institute of Materia Medica (China) Korea Research Institute of Chemical Technology (Korea) University of Auckland (New Zealand) University of Pennsylvania Johns Hopkins University Infectious Disease Research Institute University of Illinois at Chicago Texas A&M University Academic Partners

16. TB Alliance and AstraZeneca announced that they have entered into a research collaboration agreement to accelerate the discovery, development and clinical use of drugs against tuberculosis, especially drug resistant strains. May 3, 2010

17. The TB Alliance and AstraZeneca will: contribute promising TB drug discovery projects into a joint portfolio that will be co-developed focus on novel compound classes create a seamless path to clinical-stage development share resources The Collaboration

18. The TB Alliance will contribute its ongoing collaborations with several world-leading researchers at: University of Pennsylvania Rutgers University New York Medical College TB Alliance Commitment

19. Projects will come from its TB research center in Bangalore, India The joint portfolio will be resourced by a core group of scientists based at AstraZeneca’s TB research center in Bangalore, India AstraZeneca Commitment

20. Global Alliance for TB Drug Development www.tballiance.org