1. Interim analysis of a double- blind, placebo-controlled study with TMC207 in patients with Multi-Drug Resistant (MDR) Tuberculosis Karel de Beule, CDTL TMC 207

2. TMC207-C208 Trial Design Phase II, placebo-controlled, double-blind Patients with newly diagnosed smear positive MDR-TB Stratified by trial site and degree of lung cavitation 2 stage trial design Stage 1 - Safety and dose determination –8 weeks dosage TMC207/placebo and BR, then BR and 24 months follow-up –Dose regimen: 400 mg qd for 2 weeks followed by 200 mg three times weekly for 6 weeks Stage 2 - Recruiting - full 6 month dosage This presentation is a pre-planned analysis of the stage 1 results after 8 weeks of treatment

3. Stage 1 Objectives Primary Evaluate PK (adequacy of the model predicted exposure) Evaluate safety and tolerability of TMC207 compared to placebo Secondary Evaluate anti-bacterial activity of TMC207 at 8 wks vs placebo

4. Inclusion/Exclusion Criteria Male and female 18-65 years Positive sputum smear > 1+ Confirmed resistance to H and R HIV negative or HIV+ with CD4+ > 300 and no ART No previous 2nd line anti-tuberculosis agents No significant extrapulmonary TB or concomitant illness

5. Demographics Placebo N=24 TMC207 N=23 Gender - male (%)7178 Age - median (yrs)33 HIV negative (%)8887 Body weight - median (kg)51.450.0

6. Background Regimen

7. PK of TMC207 vs model predictions CONFIDENTIAL RESULTS ONLY FOR UK-CAB MEETING

8. Most frequent Adverse Events CONFIDENTIAL RESULTS ONLY FOR UK-CAB MEETING

9. Safety CONFIDENTIAL RESULTS ONLY FOR UK-CAB MEETING

10. Microbiology parameters Weekly sputum collection - culture conversion in liquid media Defined as 2 consecutive negative cultures at least 1 week apart Drug carry-over effects were prevented Analysis set = 44 patients (3 withdrawals) Serial sputum colony counting (SSCC) performed in 22 patients in overnight sputum collections

11. Culture conversion in liquid media CONFIDENTIAL RESULTS ONLY FOR UK-CAB MEETING

12. Mean log 10 CFU count over time CONFIDENTIAL RESULTS ONLY FOR UK-CAB MEETING

13. Conclusions CONFIDENTIAL RESULTS ONLY FOR UK-CAB MEETING

14. Acknowledgements - The patients who participated in our study - Dr. Andreas Diacon and team, Stellenbosch University, Cape Town - Dr. Alexander Pym and team Medical Research Council, Durban - Dr. Martin Grobusch and team, University of the Witwatersrand - Dr. Martin Bogoshi and team, Aurum Health, South Africa - Dr. Renée Krause, C. Pistorius and team, QdotPharma, South Africa -Members of the TMC207 compound development and clinical teams, Tibotec, Yardley, PA (USA) and Mechelen, Belgium.