PDPs and Alternative IP Management/Tech Transfer Strategies for Improved Global Health

1. PDPs and Alternative IP Management/Tech Transfer Strategies for Improved Global Health Gerald J. Siuta, Ph.D. Consultant, Business Development Biotechnology Industry Organization Annual Meeting Atlanta, GA May 20, 2009

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. Complex 6-9 months treatment with a 4 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 The Need for New TB Drugs

4. 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

5. 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 The TB Alliance

6. 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

7. 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

8. FDCs Our Vision 10 Days 2 Months 6 Months

9. 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

10. 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

11. Bayer HealthCare Chiron/Novartis GlaxoSmithKline Novartis Institute for Tropical Diseases sanofi-aventis Industrial Partners

12. Infectious Disease Research Institute Institute of Materia Medica (China) Johns Hopkins University Korea Research Institute of Chemical Technology and Yonsei University (South Korea) Rutgers, The State University of New Jersey Texas A&M University University of Auckland (New Zealand) University of Illinois at Chicago University of Pennsylvania New York Medical College Academic Partners

13. TB Alliance Portfolio TB ALLIANCE PROGRAMS DISCOVERY CLINICALDEVELOPMENT Lead Identification Lead Optimization Preclinical Phase I Phase II Phase III Moxifloxacin PA-824 Quinolone TBK-613 Nitroimidazoles Mycobacterial Gyrase Inhibitors Multifunctional Molecules InhA Inhibitors March, 2009 Riminophenazines Tryptanthrines Phenotypic Screening GSK Focused Screening Malate Synthase Inhibitors Protease Inhibitors Energy Metabolism Inhibitors RNA Polymerase Inhibitors Topoisomerase I Inhibitors NITD Portfolio April 2009

14. PA-824 – 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 Chiron/Novartis

15. Worldwide exclusive license in 2002 for the treatment of tuberculosis Defined scientific milestones Grant-back option Manufacturing rights No royalties in endemic countries Presently in Phase II clinical trials PA-824

16. Moxifloxacin - fluoroquinolone antibiotic Orally active Once-a-day dosage Marketed in 141 countries for the treatment of several acute respiratory and uncomplicated skin and soft tissue infections Bayer HealthCare

17. Novel mechanism of action: kills M.tb. by inhibition of DNA gyrase In vivo mouse studies showed that 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 Moxifloxacin for TB

18. 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 The Partnership

19. 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 Moxifloxacin Clinical Trials

20. 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 Bayer Commitments

21. 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) TB Alliance Commitments

22. Joint drug discovery program at GSK’s Diseases of the Developing World facility in Tres Cantos, Spain Four individual projects: Mycobacterial gyrase inhibitors InhA inhibitors Malate synthase inhibitors Focused screening GlaxoSmithKline

23. 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 GlaxoSmithKline

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