Spero Therapeutics is facing a significant setback after its oral antibiotic candidate, SPR720, failed to show effectiveness in a recent phase 2a trial and raised safety concerns. The disappointing results prompted the company to lay off 39% of its workforce to extend its cash reserves through mid-2026.
SPR720, which Spero acquired from Vertex in 2016 for an initial payment of $500,000, was designed as an oral treatment option for nontuberculous mycobacterial (NTM) pulmonary disease, a condition typically requiring lengthy and complex combination therapies. Spero’s candidate aimed to simplify this process with an oral alternative; however, the recent interim analysis showed that SPR720 not only failed to outperform a placebo but also presented dose-limiting safety issues, including three cases of reversible grade 3 liver toxicity at a 1,000 mg dose. This double blow led Spero to pause development of the drug while they assess further options.
SPR720 operates with a different mechanism than existing treatments like Insmed’s Arikayce, which is used in combination therapies for NTM infections. Spero had hoped this new approach would limit drug resistance, but the poor trial results and safety concerns have cast doubt on SPR720’s viability. This setback follows similar issues in the field, including a recent failure by AN2 Therapeutics.
The setback has led Spero to implement significant restructuring, marking the second major layoff for the company in recent years. In 2022, after the FDA rejected Spero’s application for its oral antibiotic tebipenem HBr—a candidate with potential to treat complicated urinary tract infections—the company cut 75% of its workforce, reducing its staff from 146 to just 41. Tebipenem’s failure caught the attention of GSK, which stepped in with a $66 million investment to support a new phase 3 trial, expected to complete enrollment by late 2025.
For now, Spero’s remaining team will focus on advancing tebipenem HBr and exploring options for SPR206, another antibiotic candidate targeting multidrug-resistant Gram-negative pathogens, contingent upon securing additional funding.
