1. Eight Week Randomized Trial of Treatment with Pa-824, Moxifloxacin, and Pyrazinamide in Drug Sensitive and Multi-Drug Resistant Tuberculosis July 21, 2014 20 th International AIDS Conference Daniel Everitt, MD For the NC-002 Collaborators 1 2014 International AIDS Conference

2. Participants with newly diagnosed smear positive DS and MDR Pulmonary TB NC-002 Pa-M-Z Trial: First Novel Combination Study In patients with TB sensitive to Pa, M, and Z Pa(200mg)-M-Z N=60 Pa(100mg)-M-Z N=60 H-R-Z-E N=60 Pa(200mg)-M-Z N= up to 50 Pa = PA-824 M = moxifloxacin 400 mg Z = pyrazinamide at 1500mg 2 months of treatment Randomize Serial 16 hour pooled sputum samples for CFU Count DS DR 2 2014 International AIDS Conference

3. 3 South Africa TASK Applied Science, Cape TownLab University of Cape Town Lung Institute Helen Joseph Hospital Tembisa Hospital, Tembisa Klerksdorp Tshepong Hospital KwaZulu-Natal Research Institute for Tuberculosis and HIV (K-RITH), DurbanLab Tanzania Ifakara Health Institute, BagamoyoLab NIMR- Mbeya Medical Research ProgrammeLab Investigational Sites and Laboratories 2014 International AIDS Conference

4. 4 Treatment group Total (N=207) Age (years)31 Males (%)65 Weight (kg)56 HIV-infected (%)20 Ethnicity Black (%)71 Mixed ethnicity (%)29 Enrolment Demographic Characteristics 2014 International AIDS Conference

5. Estimates of Mean Serial Log(CFU) Count Over Time Joint Bayesian NLME Regression 5 2014 International AIDS Conference

6. 6 Study Arm Log CFU Reduction per Day Over 56 Days PA200-M-Z* (N=56) 0.155 CI [0.133; 0.178] PA100-M-Z (N=54) 0.133 CI [0.109; 0.155] PA200-M-Z-MDR (N=9) 0.117 CI [0.070; 0.174] H-R-Z-E (N=54) 0.112 CI [0.093; 0.131] Daily Log CFU Reduction – 1 o Endpoint *p < 0.05 vs H-R-Z-E No differences from above when adjusted for site, HIV status or baseline CFU as baseline covariates 2014 International AIDS Conference

7. Estimates of Mean Serial log(TTP) Over Time Joint Bayesian NLME Regression 7

8. 8 Study Arm Median Time to Culture Conversion (Days) Solid Liquid PA200-M-Z 28* 49* PA100-M-Z2842 PA200-M-Z MDR 3556 H-R-Z-E3556 Time to Culture Conversion – 2 o Endpoint *Statistically significant differences compared to HRZE for both solid and liquid culture 2014 International AIDS Conference Culture Conversion is the Time when Culture is First Negative

9. 9 Study Arm Conversion to Negative Day 56 (%) Solid Liquid PA200-M-Z94.371.4* PA100-M-Z82.965.7* PA200-M-Z- MDR 62.550.0 Rifafour87.537.8 Eight Week Culture Conversion – 2 o Endpoint *Statistically significant difference from HRZE for liquid culture only 2014 International AIDS Conference

10. Log CFU Daily Decreases and Pearson Correlation Coefficients Study / ArmLog CFU Daily (Days 7-14) Log CFU Daily (Days 7-56) Correlation Coefficient H-R-Z-E (N=15) Pa100-M-Z (N=16) Pa200-M-Z (N= 13) 0.13 0.16 0.14 0.12 0.13 0.14 0.98 0.90 0.96 2014 International AIDS Conference 10 Data from Participants Enrolled in the EBA Substudy

11. Summary of Safety Findings 11 Grade 1 to 4 Treatment-Emergent Adverse Events SeverityStatistic*PA100- M-Z (N=60) PA200- M-Z (N=62) H-R-Z-E (N=59) PA200- M-Z MDR (N=26) Total (N=207) Grade I%7277786975 Grade II%4250465046 Grade III%3032252329 Grade IV%515108 * % = Percentage of patients with at least one AE in each category

12. 12 Pa-M-Z Regimen was statistically significantly better than the H-R-Z-E control for the primary and 3/5 key secondary endpoints – Greater reduction in colony counts over 56 days – More rapid time to culture conversion – Higher conversion to negative at 8 weeks – Nearly twice the number converted in liquid culture No significant difference in response for HIV infected patients Similar effects for patients with MDR-TB, albeit with small numbers Safety comparable to control Next Step: The STAND Phase 3 Trial NC-002 Summary of Key Results and Next Steps 2014 International AIDS Conference

13. Participants with newly diagnosed smear positive DS- and MDR-TB The STAND Trial - Phase 3 Trial of Pa-M-Z “Shortening Treatment by Advancing Novel Drugs” Pa(100mg)-M-Z N=300 Pa(200mg)-M-Z N=300 H-R-Z-E N=300 Pa(200mg)-M-Z N= up to 300 Z = pyrazinamide at 1500mg Pa = PA-824 M = moxifloxacin 400 mg 4 months of treatment Randomize DS DR 13 Pa(200mg)-M-Z N= 300 6 months of treatment 12 & 24 mos f/u after randomization 2014 International AIDS Conference

14. 14 Robert Schall – University of the Free State, and Quintiles Biostatistics, Bloemfontein, SA Christo Van Niekerk – TB Alliance, Pretoria, SA Almari Conradie – TB Alliance, Pretoria, SA Carl Mendel – TB Alliance, New York, USA Rodney Dawson – University of Cape Town Lung Institute, Cape Town, SA Andreas Diacon – Stellenbosch University, Tygerberg, and TASK Applied Science, Bellville SA Divan Burger – University of the Free State, and Quintiles Biostatistics, Bloemfontein, SA To the Patients with Tuberculosis who Participated, volunteer Community Advisory Boards, and Lead Investigators and Colleagues: Sincere Acknowledgments: 2014 International AIDS Conference

15. 15 2014 International AIDS Conference TB Alliance Supporters Bill & Melinda Gates Foundation European Commission United States Food and Drug Administration Irish Aid National Institute of Allergy and Infectious Diseases UK aid United States Agency for International Development AIDS Clinical Trial Group Global Health Innovative Technology Fund UNITAID Australian AID Thanks to all those who support our mission for better, fast TB drugs