Global New TB Drug Pipeline * Discovery Preclinical Development Clinical Development JL A Diarvlauinotines pst inhibitors InhA Inhibitor uthenium(tnComplexes arvisulfonamides Translocase-1 inhibitors, dp, mpi Gxazolidinones, yrimidines Dpre1,PKS33 Sauaramides “New chemical class. Known chemical classes are color coded: fluor CPZEN-45* —-BT2-043* OPC Delpazolid saTB0s2* @sk-070"~—«*187882* (801-0371) Spectinamice - TBA-7371* PETZ169" sQ-109* 1810* TBAI-587 208" SPR-720 a Sutezolid (pvxeaaey* (PNU-100480) TBI-166* T8223, TB.47* uinolone,rfarnycin, oxzzoidinone, ritroimidazole, iarylquinaline, benzothiazinone, imidazopyridine amide. New Molecular Entities not yet approved, being developed for TB or only conditionally approved for “TB. Showing most advanced stage reported for cach. Details for projects lsted can be found at ntp:/wwn.newtbdrugs. Ongoing projects without a lead compound series identified can be viewed at nttn-//wuw.newtbdrues.orz/pineline/discovery @ Delamanid (OPC-67683) Pretomanid (PA-824) WORKING GROUP fo ON NEW TB DRUGS www.newtbdrugs.org Updoted: 1une 2017Global New TB Drug Pipeline* Preclinical Development Clinical Development r A ti Ve i ED Daa. cums weteorite prz.oa3" OPC-167832* —Delpazolid Bedaquiline (TMC-207) LcB01-0371) Cyclopeptide TBA-7371* PBTZ169* f 1 Delamanid (OPC-67683) SATBOS2* . $Q-109" 5 . GSK-070* 9203" Pretomanid (PA-824) pectinamide 1810' > Sutezolid inophenazine TBAI-587 (PNU-100480) TBr-166 Ona TBr-223, Gyrase inhibitor SPR-720 (pVXe-486)" Oxazole TB-47" New chemical class™ Known chemical classes are color coded: fluoroquinolone, rifamyci ‘oxazolidinone, nitroimidazole, diarylquinoline, benzothiazinone , midazopyridine amide. + New Molecular Entities not yet ay ved, being developed for TB or only conditionall approve rT showing ost advnced soge repre or eash Sea tor pjess ated @ NS) WORKING GROUP Ongoing projects without a lead compound series identified can be viewed at www.newtbdrugs.org [ae nwboge ratte dnc eeeGlobal TB Drug and Regimen Clinical Research , Ongoing Clinical Development Research: Strategy/Optimization/Regimen Development > errr peer Bedaquiline-Delamanid (ACT 5242) Bedaquiline - Pretomanid - Pyrazinamide (BPaZ) Bedaquiline - Pretomanid — Moxifloxacin - Pyrazinamide (BPaMZ) Levofloxacin with OBR for MDR-TB {oPTI-Q) Linezolid Dose-Ranging Nitazoxanide High Dose Rifampicin (PANACEA) ‘TB PRACTECAL - regimens with Bedaquiline-Pretomanid-Linezolid Bedaquiline-STREAM MDR-TB Trial Stage 2 with oral OBR (9 mo) or OBR with injectables (6 mo) Bedaquiline-Pretomanid-Linezolid (Nix-TB Regimen) Delamanial (OPC-67683) with OBR for MDR-TB High Dose Rifampicin for DS-TB (RIFASHORT) Rifapentine - Moxifloxacin for DS-TB Pretomanid-Moxifloxacin- Pyrazinamide Regimen (STAND) Known chemical classes are color coded: fluoroquinolone, rifamyein, oxazolidinone, nitroimidazole, diarylquinoline, benzothiazinone , imidazopyridine amide. ‘Strategy trials, regi yen development, open label, repurposed drug studies. Details for projects listed can be found at httpi//www.newtbdrugs.org/pipeline/clinical 2 OBR = Optimized Background Regimen Bedaquiline-Linezolid with OBR for MDR-TB (NEXT Trial) endTB 5-Regimen Trial for MOR TB @ WORKING GROUP @ ON NEW TB DRUGS www.newtbdrugs.org Updated: June 2017Global TB Drug Discovery Pipeline + =n Astinomycete Metabolites (U ILL Chicago, Myongii U) Novel Hit-to-Lead Programs (Lilly DDi) GATB ‘Adamantanids (U ILL Chicego) ‘Whole-cell Hit-to-Lead (GSK, GATE) Menaquinone Synthase Inhibitors (CSU) M.th Energy Metabolism inhibitors (GATE, T6DA) Isoprenoid Biosynthesis Inhibitors (Lilly DDi)_ ‘Whole-Cell Hit-to-Lead (GATE, Sanofi RNA Polymerase Inhibitors (GATE) Gloc/Pe2 (care) POA Prodrugs (GATB, Yonsei) PEPCK (GATB, Roche, TAMU) * beta for project ete can be found at hp wuna.neurruge ong/sipaline discovery. and clinical development projects ean be viewed at hipi/wi.newiberugs oa/oipline phy ‘Abbreviations of Developers: A*Star- Agency for Science Technology and Research CSU. Colorado State University; FAPESP So Paulo Research Foundation; GATB Global Alliance for Drug Development (78 aliancel; 6SK-Glxosmithkline; Lily DDHLly 78 Orug Discovery Initiatives RL-Research Insttte; SPRINT TB-Sngapore Programme of Research Investigating New Approaches to Treatment of TB; St. Jude St. ude Children’s Research Hospital TAMU Texas A&M University; TBDA-TB Orug Accelerator U-Universitys UML University of lini; UPenn- Univesity of Pennsyvania; U Ten University of Tennessee: ULUnwversity ofzurch Diarylquinolines (GATB, U Auckland, Janssen) Diarythazoles (TEA) InhA Inhibitors (65K) Doré Inhibitors Azaindoles(Calibr) RutheniumiI}phosphine/picolinate Complexes (FAPESP/C,22) Spectinamides (st. Jude, U Tenn, CSU, Uz, Microbictx) Macrolides(GATB, Sarof) Drpé Inhibitors (GATB) lp [SPRINT TB /A* Star) ‘Mmpl3 (GATE, TBDA} xazolidinones (GATE, IMM, TEOA) Pyrimidines DprE3 (GATE, GSK, TBDA) Aryl Sulfonamides (GATB, GSK, TEDA) S13 (GATE, DDU, TAMU, GSK, TBDA) Squaramides (GATB, TADA, Sanofi) @\) WORKING GROUP @ ON NEW TB DRUGS www.newtbdrugs.org Updated: June 2017