Table 1.
Antibiotics in clinical development; adapted from WHO analysis (current to November 2021; World Health Organization, 2022).
| INN (company code) | Phase | Antibiotic class | Route of administra‐tion | Developer | Expected activity against priority pathogens | Innovation | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| CRAB | CRPA | CRE | OPP a | NCR | CC | T | MoA | |||||
| Solithromycin (T‐4288) | NDA b | Macrolide | i.v. and oral | Fujfilm Toyama Chemical | / | / | / | ● | ‐ | ‐ | ‐ | ‐ |
| Sulopenem; sulopenem etzadroxil / probenecid | 3 c | β‐Lactam (penem) | i.v. and oral | Iterum Therapeutics | ○ | ○ | ○ d | / | ‐ | ‐ | ‐ | ‐ |
| Durlobactam (ETX‐ 2514) + sulbactam | 3 | DBO‐BLI/PBP2 binder + β‐lactam‐BLI/ PBP1,3 binder | i.v. | Entasis Therapeutics | ● | ○ | ○ | / | ‐ | ‐ | ‐ | ‐ |
| Taniborbactam (VNRX‐5133) + cefepime | 3 | Boronate BLI + β‐lactam (cephalosporin) | i.v. | VenatoRx Pharmaceuticals / GARDP | ○ | ● | ● | / | ? | ✓ | ‐ | ‐ |
| Enmetazobactam (AAI‐101) + cefepime | 3 | BLI + β‐lactam (cephalosporin) | i.v. | Allecra Therapeutics | ○ | ○ | ○ e | / | ‐ | ‐ | ‐ | ‐ |
| Zoliflodacin | 3 | Spiropyrimidenetrione (topoisomerase inhibitor) | oral | Entasis Therapeutics / GARDP | / | / | / | ● | ✓ | ✓ | ‐ | ✓ |
| Gepotidacin | 3 | Triazaacenaphthylene (topoisomerase inhibitor) | i.v. and oral | GSK | / | / | / | ● | ? | ✓ | ‐ | ✓ |
| Nafithromycin (WCK‐4873) | 3 | Macrolide | Oral | Wockhardt | / | / | / | ● | ‐ | ‐ | ‐ | ‐ |
| Benapenem | 2/3 | β‐Lactam (carbapenem) | i.v. | Xuanzhu Biopharm f | ○ | ○ | ○ | / | ‐ | ‐ | ‐ | ‐ |
| Afabicin (Debio‐1450) | 2 | Pyrido‐enamide (FabI inhibitor) | i.v. and oral | Debiopharm | / | / | / | ● | ✓ | ✓ | ✓ | ✓ |
| Zidebactam + cefepime | 1 g | DBO‐BLI/ PBP2 binder h + cephalosporin | i.v. | Wockhardt | ● | ● | ● | / | ‐ | ‐ | ‐ | ‐ |
| OP0595 (nacubactam) + meropenem | 1 | DBO‐BLI/PBP2 binder h + β‐lactam (carbapenem) | i.v. | Meiji Seika | ○ | ○ i | ● | / | ‐ | ‐ | ‐ | ‐ |
| ETX0282 + cefpodoxime proxetil | 1 | DBO‐BLI/PBP2 binder h + β‐lactam (cephalosporin) | Oral | Entasis Therapeutics | ○ | ○ | ● | / | ‐ | ‐ | ‐ | ‐ |
| ARX‐1796 (oral avibactam prodrug) | 1 | DBO‐BLI + β‐lactam (undisclosed) | oral | Arixa Pharmaceuticals / Pfizer j | ○ | ○ | ● k | / | ‐ | ‐ | ‐ | ‐ |
| XNW4107 + imipenem + cilastatin | 1 | BLI + β‐lactam (carbapenem) / degradation inhibitor | i.v. | Sinovent | ? | ? | ? | ? | ? | ? | ? | ? |
| VNRX‐7145 + ceftibuten | 1 | Boronate‐BLI + β‐lactam (cephalo‐sporin) | Oral | VenatoRx Pharmaceuticals | ○ | ○ | ● | / | ? | ✓ | ‐ | ‐ |
| QPX7728 + QPX2014 | 1 | Boronate‐BLI + undisclosed | i.v. | Qpex Biopharma | ● | ● | ● | / | ? | ‐ | ‐ | ‐ |
| QPX7728 + QPX2015 | 1 | Boronate‐BLI + undisclosed oral β‐lactam | Oral and i.v. | Qpex Biopharma | ○ | ○ | ● | / | ? | ‐ | ‐ | ‐ |
| SPR‐206 | 1 | Polymyxin | i.v. | Spero Therapeutics | ● | ● | ● | / | ‐ | ‐ | ‐ | ‐ |
| MRX‐8 | 1 | Polymyxin | i.v. | MicuRx | ● | ● | ● | / | ‐ | ‐ | ‐ | ‐ |
| QPX9003 | 1 | Polymyxin | i.v. | Qpex Biopharma | ? | ? | ? | ? | ? | ? | ? | ? |
| KBP‐7072 | 1 | Tetracyclin | Oral | KBP BioSciences | ● | ○ | ○ | ● | ‐ | ‐ | ‐ | ‐ |
| EBL‐1003 (apramycin) | 1 l | Aminoglycoside | i.v. | Juvabis | ● | ? | ● | / | ‐ | ‐ | ‐ | ‐ |
| TXA709 | 1 | Difluorobenz‐amide (FtsZ inhibitor) | Oral and i.v. | TAXIS Pharmaceuticals | ○ | ○ | ○ | ● | ✓ | ✓ | ✓ | ✓ |
| RG6006 (Abx MCP) | 1 | Macrocyclic peptide | i.v. | Roche | ? m | ? | ? | ? | ? | ? | ? | ? |
| BWC0977 | 1 | Topo‐isomerase | i.v. | Bugworks Research | ? | ? | ? | ? | ? | ? | ? | ? |
Pathogen activity: ● active;? possibly active; ○ not or insufficiently active; / activity not assessed, as the antibiotic is focused and developed for only either Gram‐positive cocci or Gram‐negative rods. Agents not active against critical priority pathogens were assessed for activity against OPP, which includes the WHO high and medium priority pathogens.
Innovation assessment: ✓ criterion fulfilled;? inconclusive data; − criterion not fulfilled.
BLI, β‐lactamase inhibitor; CC, chemical class; CRAB, carbapenem‐resistant A. baumannii; CRE, carbapenem‐resistant Enterobacterales; CRPA, carbapenem‐resistant P. aeruginosa; ESBL, extended‐spectrum β‐lactamase; FabI, enoyl‐acyl carrier protein reductase; DBO, diazabicyclooctane; FtsZ, cell division protein named after corresponding mutant phenotype, filamenting temperature‐sensitive mutant Z; GARDP, Global Antibiotic Research and Development Partnership; i.v., intravenous; KPC, K. pneumoniae carbapenemase; MoA, new mode of action; NCR, no cross‐resistance; NDA, new drug application; OPP, other priority pathogen; PBP2, penicillin‐binding protein 2; T, new target; uUTI, uncomplicated urinary tract infection; WHO, World Health Organisation.
OPP target pathogens – solithromycin: S. pneumoniae; nafithromycin: S. aureus and S. pneumoniae; zoliflodacin: N. gonorrhoeae; gepotidacin: N. gonorrhoeae and E. coli; TNP‐2198: H. pylori; afabicin, TNP‐2092, KBP‐7072 and TXA‐109: S. aureus.
Solithromycin NDA for otorhinolaryngological infections was submitted in Japan in April 2019.
Iterum will undertake an additional Phase 3 uUTI study of sulopenem etzadroxil before any NDA resubmission.
Active against ESBL‐producing cephalosporin‐resistant Enterobacterales but not carbapenem‐resistant Enterobacterales.
Active against ESBL‐producing cephalosporin‐resistant Enterobacterales and some KPC‐producing CRE.
Xuanzhu Biopharm is a subsidiary of Sichuan Pharmaceutical Holdings but possesses fully independent intellectual property rights.
A Phase 3 trial for zidebactam + cefepime was registered in July 2021 for cUTI or acute pyelonephritis (NCT04979806).
The DBO‐BLIs zidebactam, OP0595 (nacubactam) and ETX0282 also have some antibacterial activity and have been classified as β‐lactam enhancers.
Activity against AmpC‐β‐lactamase producing and KPC‐producing CRPA.
The original developer, Arixa Pharmaceuticals, was acquired by Pfizer in October 2020.
Active against KPC but not MBL‐producing Enterobacterales.
Previously used as an antibacterial treatment in animals.
RG6006 is being developed to treat A. baumannii infections.