Not much went right for Spero Therapeutics’ SPR720 in its phase 2a trial. An interim analysis revealed a double blow to the oral antibiotic candidate, which both failed to beat placebo and showed signs of liver toxicity. Spero responded by laying off 39% of its employees to extend its cash runway to mid-2026.
Spero identified SPR720, which it picked up from Vertex for $500,000 upfront in 2016, as a potential oral treatment for nontuberculous mycobacterial pulmonary disease. The biotech advanced the candidate in the belief existing treatments are often ineffective and always inconvenient, with patients needing to receive lengthy and complex combination regimens that include injected and inhaled antibiotics.
Hopes for Spero’s program crumbled in the harsh light of phase 2a data. An interim analysis showed insufficient separation from placebo—casting significant doubts on efficacy—and adverse events that raise concerns about the safety of SPR720.
Spero saw potential dose-limiting safety issues in people who received 1,000 mg of SPR720 orally once daily. The safety issues included three cases of reversible grade 3 hepatotoxicity. The mix of lackluster efficacy and worrying safety led Spero to suspend its current development program. Spero will evaluate other potential paths forward as the remaining data are collected and analyzed.
SPR720 has a different mechanism than rival molecules such as Insmed’s approved Arikayce. The mechanism suggests the asset might largely avoid drug resistance and could play a role in combinations, which are widely used in the setting. But the lack of efficacy and safety signals raise doubts about the future of SPR720, dealing a further blow to a space still reeling from AN2 Therapeutics’ flop.
Spero’s employees are paying the price for the setback. The biotech is restructuring and laying off 39% of its staff to extend its cash runway into the middle of 2026. Spero laid off 75% of its staff in 2022, reducing its head count from 146 to 41 full-time employees.
The remaining staffers will focus on running an ongoing phase 3 trial of tebipenem HBr and preparing for a phase 2 trial of SPR206 that is dependent on non-dilutive funding. Tebipenem is the candidate that triggered the earlier round of layoffs. The FDA rejected a filing for approval of tebipenem, which could become the first oral carbapenem-class antibiotic used in complicated urinary tract infections, in 2022.
GSK swooped in to rescue the program, paying $66 million that enabled Spero to design and start a new phase 3 trial. The biotech expects to complete enrollment in the trial in the second half of 2025. SPR206 is a polymyxin that has shown activity against multidrug-resistant Gram-negative pathogens.