R&D Update Carl M. Mendel, M.D. SHA Meeting October 28, 2013 Paris, France

2013 Q3 Discovery Early Development Late Development Lead identification Lead Optimization PRECLINICAL DEVELOPMENT Phase 1 Phase 2A Phase 2B Phase 3 Phase 4 TBA-354 Preclinical TB Regimen Development JHU TBI-166 IMM ATP Synthesis Inhibitors Calibr Energy Metabolism Inhibitors AZ/University of Penn Whole-Cell Hit-to-Lead Program AZ Whole-Cell Hit-to-Lead Program Sanofi Whole-Cell Hit-to-Lead Program NITD GSK RNA Polymerase Inhibitors Rutgers University Mycobacterial Gyrase Inhibitors GSK Pyrazinamide Analogs Yonsei University Diarylquinolines Janssen/University of Auckland/UIC Indazoles GSK DprE Inhibitors Calibr Cyclopeptides Sanofi Macrolides Sanofi Novel Structural Series NITD Ureas Sanofi NC-003 Bedaquiline/ Clofazimine/ Pyrazinamide PA-824/ Bedaquiline/ Clofazimine/ Pyrazinamide PA-824/ Bedaquiline/ Clofazimine PA-824/ Bedaquiline/ Pyrazinamide NC-002 REMox-TB Optimized Pediatric Formulations PA-824/ Moxifloxacin/ Pyrazinamide (PaMZ) Moxifloxacin/ Isoniazid/ Rifampin/ Pyrazinamide Bayer, MRC, UCL Moxifloxacin/ Rifampin/ Pyrazinamide/ Ethambutol Isoniazid/ Rifampin/ Pyrazinamide/ Ethambutol TB Alliance R&D Partners: AstraZeneca (AZ) New York Medical College Bayer Healthcare AG (Bayer) Rutgers University Beijing Tuberculosis and Thoracic Tumor Research Institute Sanofi Stellenbosch University Calibr University College London (UCL) GlaxoSmithKline (GSK) University of Auckland Institute of Materia Medica (IMM) University of Illinois at Chicago (UIC) Janssen (Johnson & Johnson) University of Pennsylvania School of Medicine Johns Hopkins University (JHU) Medical Research Council (MRC) Yonsei University Novartis Institute for Tropical Diseases (NITD)

TB Alliance Strategic Focus R&D portfolio progression Novel regimen development Unified DS/DR development pathway (even for MDR market) Driven by target product profile Discovery, preclinical, early clinical, Phase 3, market Connect the dots Maximize impact Delivering products to markets Understanding of/focus on market needs Full approval at launch Know how (and how long) to use regimen at launch—can still be accelerated Time to impact, time to achieve, cost Pediatric drug development Partnering/sustainable funding models

2013 Progress--Discovery IND filing of next generation nitroimidazole (TBA-354) Enter Ph 1 clinical trials next quarter Multiple lead optimization programs continue to advance Identification of novel, non-cytotoxic, potent chemical matter sensitive to known drug-resistant Mtb clinical isolates Continuing identification of promising drug combinations in mouse models Continuing improvement of understanding of preclinical models

2013 Progress--Clinical Clinical trials in 2013 REMox NC-002 NC-003 TMC207/rifabutin DDI (with NIH) PA-824/efavirenz DDI (with NIH) PA-824 TQT study (with NIH)

Phase 3 REMoxTB Trial Design Randomized, Double-blind; Non-inferiority Treatment Duration (months) 1 2 3 4 5 6 Intensive Continuation 630 participants Standard Regimen HRZE HR Placebos 630 participants Moxifloxacin for Ethambutol HRZM HRM Placebos 630 participants Moxifloxacin for Isoniazid MRZE MR Placebos All participants followed for 12 months post-treatment H = isoniazid; M = moxifloxacin; R = rifampin; Z = pyrazinamide; E = ethambutol 6

REMox Study Status Update Number of Patients Randomized: 1931 First Patient In: 1Q08 Last Patient In: 21Jan12 Last Patient Last Visit (M18): 29July13 Laboratory Data Entry: 15Nov13 Database Lock: 25Nov13 Topline Results: Jan14 Clinical Study Report: March14 New Drug Application: July14 7

Z = pyrazinamide Pa = PA-824 M = moxifloxacin First Novel Combo SSCC: NC-002 In patients with TB sensitive to Pa, M, and Z Participants with newly diagnosed smear positive DS TB Pa(200mg)-M-Z N=60 Pa(100mg)-M-Z Rifafour N=50 DS 2 months of treatment Randomize DR Serial 16 hour pooled sputum samples for CFU Count Z = pyrazinamide Pa = PA-824 M = moxifloxacin

Third Novel Combo BA Study: NC-003 Z=pyrazinamide, C=clofazimine, Pa=PA-824, J=bedaquiline Participants with newly diagnosed smear positive DS TB C J-C-Z J-Pa-C J-Pa-C-Z Rifafour Z 14 daily doses Randomize 15 per group Serial 16 hour pooled sputum samples for CFU count J-Pa-Z

2013 Progress – Capacity Building Biomarker repository Multi-site quantitative culture capabilities in Ph 2 Ph 3 site and laboratory selection Capabilities, regulatory environment, geographic diversity Bactericidal activity analytics (manual plus program) “Universal” mycolaboratory manual

Major Accomplishments 2013 2013 witnessed a huge amount of progress Completion of REMox TB: significant undertaking (48 sites in 9 countries); potential to be 1st new (new class) DS-TB treatment in 50 years Completion of NC-002: 1st regimen trial to move beyond today’s treatment paradigm; potential to shorten treatment for DS & some MDR-TB, promising for HIV/TB co-infection Completion of NC-003: Second-generation regimen trial; potential to dramatically expand the number of people that can benefit from bedaquiline Initiation of Pediatric Program: Work underway to deliver a FDC of the first-line treatment by 2016 2014 will be an exciting year!

TB Alliance Supporters Thanks to all those who support our mission for better, faster-acting TB regimens United States Agency for International Development Bill & Melinda Gates Foundation UNITAID UK aid United States Food and Drug Administration National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group European Commission Global Health Innovative Technology Fund Australian AID Irish Aid