Spero Therapeutics Discontinues Antibiotic Program in Latest Pipeline Reprioritization

Spero Therapeutics, a Cambridge, Massachusetts-based antibiotics biotech, has announced the discontinuation of its SPR206 program, a next-generation polymyxin antibiotic, as part of its ongoing pipeline review and reprioritization efforts. This decision marks another setback for the company, which has been streamlining its operations and pipeline in recent months.

SPR206 Program Halted

SPR206, which had shown promise in preclinical studies against multidrug-resistant (MDR) Gram-negative pathogens, was being prepared for a phase 2 trial in hospital- and ventilator-acquired bacterial pneumonia. The development of this drug candidate had received support from several U.S. government agencies, including the Department of Defense, the National Institute of Allergy and Infectious Diseases, the National Institutes of Health, and the Department of Health and Human Services.

Esther Rajavelu, Spero's interim President and CEO, expressed gratitude to the partners and government agencies that had supported the program, as well as to the Spero team members who had advanced SPR206 to a phase 2-ready asset. However, the company determined that discontinuing the program was necessary based on its first-quarter 2025 pipeline review.

Recent Pipeline Setbacks and Restructuring

This latest development follows a series of challenges for Spero Therapeutics. In October 2024, the company halted work on SPR720, an oral antibiotic for non-tuberculous mycobacterial pulmonary disease, after it failed to outperform placebo and showed signs of liver toxicity in a phase 2 trial. This disappointment led to another round of layoffs at the company.

Spero's tebipenem HBr program, an oral carbapenem antibiotic, has also faced difficulties. The FDA rejected an approval filing for tebipenem HBr in 2022, which would have made it the first oral carbapenem-class antibiotic for complicated urinary tract infections. However, GSK later partnered with Spero, providing $66 million to design and initiate a new phase 3 trial for the drug. An interim analysis of this trial is expected in the second quarter of 2025.

Financial Outlook and Future Plans

Despite these setbacks, Spero Therapeutics entered 2025 with $52.9 million in cash. The company expects this funding, along with milestone payments from its partnership with GSK, to support operations into the second quarter of 2026.

Spero is currently reviewing data from the failed SPR720 program, acknowledging the high unmet need for new therapies in non-tuberculous mycobacterial pulmonary disease. The company aims to make an informed decision on the program's future based on a complete data analysis.

As Spero Therapeutics continues to navigate challenges in antibiotic development, its experience reflects broader industry trends. Many large pharmaceutical companies have abandoned antibiotic and antifungal research due to low returns on investment. However, some players, such as GSK, remain committed to addressing critical infectious disease challenges through strategic partnerships and ongoing clinical development efforts.