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

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

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

The Need for New TB Drugs 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

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

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 50 FTE in-house

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)

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

Our Vision FDCs 10 Days 2 Months 6 Months

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

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

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

TB Alliance Portfolio TB ALLIANCE PROGRAMS DISCOVERY CLINICAL DEVELOPMENT 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

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

Academic Partners 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

May 3, 2010 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.

The Collaboration 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

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

AstraZeneca Commitment 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

Global Alliance for TB Drug Development www.tballiance.org