1. TB Alliance-Bayer Partnership Background Information

2. Tuberculosis – a Global Epidemic 2 billion people are 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 Multi-Drug Resistant-TB/ year Biggest killer of women of childbearing age

3. The TB Alliance To develop world-class, affordable medicines for the poor and cure a disease that kills someone every 15 seconds. Mission

4. 1.Active Disease 2.MDR-TB 3.TB/HIV Co-Infection 4.Latent TB Infection TB Alliance Priorities Based on impact and feasibility

5. Reaching Patients: AAA Strategy Affordability –Appropriate pricing for developing countries –Leverage/access IP rights Adoption –Orally available, easy to use, compatible with ARVs –Leveraging WHO treatment protocol for TB Access –Procurement & distribution –Funding via Global Fund to Fight AIDS, TB, Malaria or IFFFm

6. Historic Opportunity to Develop New Therapeutic Options for TB 19502010 1952 1 st regimen: Streptomycin PAS Isoniazid 1963 Rifampin (RIF) discovered 1970 BMRC Trials add RIF 1974 BMRC Trials add RIF & PZA 2005 Trials substitute Moxifloxacin into regimen 1970 1960 1954 Pyrazainimide (PZA) discovered – but liver toxicity Rx lasts from 12-24 months Rx shortened to 9 months Rx shortened to 6 months Rx target: 3-4 months Standard Therapy 2 months: rifampin, isoniazid, pyrazinamide, ethambutol + 4 months: rifampin, isoniazid Standard Regimen by 1960s based on 1952 drugs 1980

7. Bayer: A Strong Tradition in Anti-Infectives PRONTOSIL 1935: Sulphonamide therapy that drastically reduced death caused by infectious diseases; research led by Nobel Prize winner and Bayer scientist, Professor Dr. Gehard Domagk ZEPHIROL 1935: External disinfectant that treat wound infections CONTOBEN (Thiacetazone) 1950: Treatment of tuberculosis NEOTEBEN (Isoniazid) 1952: Long-term therapy of tuberculosis (based on Dr. Domagk’s work) CIPROFLOXACIN 1987: Fluoroquinolone for treatment of urinary tract infections – 14 FDA-approved indications MOXIFLOXACIN 1999: Fluoroquinolone for treatment of respiratory tract infections – 7 FDA- approved indications

8. Moxifloxacin Timeline (US) Complicated skin and skin structure infections Community acquired pneumonia due to multi-drug resistant Streptococcus pneumoniae Uncomplicated skin and skin structure infections Acute bacterial sinusitis (ABS), acute bacterial exacerbations of chronic bronchitis (ABECB), community-acquired pneumonia (CAP) Community acquired pneumonia due to Penicillin- Resistant Streptococcus pneumoniae 2001 2005 2004 2003 1999

9. Moxifloxacin Basics  Description  Discovered and manufactured by Bayer  Antibiotic in the fluoroquinolone class  Approved in 1999 in Germany and by U.S. FDA  Currently approved in 104 countries (oral and/or IV formulation)  Safety  More than 42 million patient uses worldwide for all indications  Generally well-tolerated  Most common, mild side effects include nausea, diarrhea, and dizziness  Current Indications  Acute bacterial sinusitis (ABS)  Acute bacterial exacerbations of chronic bronchitis (ABECB)  Community acquired pneumonia (CAP)  Uncomplicated and complicated skin and skin structure infections (uSSSI, cSSSI)

10. Investigators at Johns Hopkins University found that substitution of moxifloxacin for isoniazid in a mouse model decreased treatment time by two months Moxifloxacin has demonstrated activity against mycobacterium tuberculosis in both in vitro and in vivo published studies Moxifloxacin has an excellent oral bioavailability & long biological half-life (T1/2) Moxifloxacin has a low potential for drug-drug interaction because it is not metabolized by the cytochrome P-450 enzyme system Moxifloxacin has a demonstrated safety record: 42 million patient uses for all indications worldwide Moxifloxacin for TB Scientific Rationale

11. In an animal study*, moxifloxacin regimen shortened treatment duration by 2 months 0 1 2 3 4 5 6 7 8 9 10 0123456 Duration of treatment (months) Log CFU in entire lung Untreated 2 months rifampin, isoniazid and pyrazinimide followed by 4 months rifampin and isoniazid 2 months rifampin, moxifloxacin and pyrazinimide followed by 4 months rifampin and moxifloxacin *In vivo data does not predict clinical response. Legend

12. Overview of Clinical Development Program TrialStudy DesignLocationsPatient Size Status CDC #27 Moxifloxacin replaces Ethambutol USA, Canada, Uganda, South Africa 336Complete 6/05 CDC #28 Moxifloxacin replaces IsoniazidUSA, Canada, Uganda, South Africa as well as Brazil, Spain 410Recruiting to commence in 2005 JHU Moxifloxacin replaces Ethambutol Brazil170Trial initiated 2/05 UCL- BMRC Moxifloxacin replaces Ethambutol Moxifloxacin replaces Isoniazid Tanzania, SA, Zambia 1500Recruiting to commence in early 2006

14. TB Alliance-Bayer Relationship Goals –Coordinate clinical trials to support registration of moxi- based regimen for TB at affordable price –Common GCP/GMP-based clinical trial standards –Unified safety data base –Clinical data-sharing Affordability –For patients most “in need” By-products for drug development –Chart regulatory path –Evaluate/validate potential surrogate markers –Build clinical trial capacity

15. Partnership Roles TB AllianceBayer Partial fundingSupply of Drug Strategy & coordinationConsultancy Facilitate compliance with regulatory standards Regulatory sponsor Assurance of AAA* *Affordability, Accessibility, Adoption Commitment to AAA

16. TB Alliance-Bayer Partnership Background Information