Compound

SPR720

Spero Therapeutics, LLC
Names
SPR720, VXc-100, VXc-486
Chemical Class:
Ethyl urea benzimidazole
Name of Target:
GyrB ATPase
Description

News Release January 2019:

CAMBRIDGE, Mass., Jan. 29, 2019 (GLOBE NEWSWIRE) -- Spero Therapeutics, Inc. (Nasdaq:SPRO), a multi-asset clinical-stage biopharmaceutical company focused on identifying, developing and commercializing novel treatments for multidrug-resistant (MDR) bacterial infections, announced today that it has initiated a Phase 1 clinical trial of SPR720, an orally administered antimicrobial agent being developed for the treatment of non-tuberculous mycobacterial (NTM) infections.

 

Microbe 2017 Poster:

 DNA gyrase is a highly conserved topoisomerase composed of two subunits, GyrA and GyrB, and is critical for bacterial DNA replication. Quinolones target the GyrA subunit and GyrB inhibitors, some with anti-mycobacteria activity, have been reported, but none have yet reached the market. Data show efficacy for two GyrB inhibitors, SPR720 (formerly pVXc-486) and SPR750, in a murine chronic Mtb infection model.  Treatment with SPR720 at 100 mg/kg administered twice daily was effective in this chronic infection model with a 2.5-log CFU decrease compared with early controls. This CFU decrease was similar to that of moxifloxacin and isoniazid in this study. SPR750 exhibited more modest activity with a 1.0-log decrease of CFUs. PK analyses showed good dose-proportional exposures after oral administration. Conclusions: Treatment with GyrB inhibitors, SPR720 and SPR750, showed efficacy in a murine chronic Mtb infection model. These data suggest that future studies are warranted to determine if they could replace quinolones in MDR/XDR drug therapy regimens.