oral GyrB inhibitor
Ph. II for NTM-PD
phosphate prodrug of SPR719
bioRxiv, December 9, 2022
Spero Therapeutics, Cambridge, MA
What is it? SPR720 (pVXc-486) is an oral prodrug of a dual inhibitor of the bacterial DNA gyrase and topoisomerase IV ATPase catalytic domains, GyrB and ParE. The molecule was in-licensed by Spero Therapeutics, a 2014 “Fierce 15” startup, from Vertex (WO2014014845A1, US20140031318), and is now Spero’s lead development program after Spero was issued a CRL for tebipenem and out-licensed tebipenem to GSK. Last year, the FDA lifted its clinical hold on SPR720, which was originally placed due to mortality findings in non-human primates (NHPs), despite demonstration of safety in a Ph. I trial (NCT03796910, 500-1,500 mg QD). The molecule now continues its Ph. II study in nontuberculous mycobacterial pulmonary disease (NTM-PD) due to Mycobacterium avium complex (MAC) (NCT05496374). Why…