Spero Therapeutics has suspended the development of its antibiotic SPR720, after the therapy failed to meet the primary endpoint in a Phase IIa trial in patients with non-tuberculous mycobacterial pulmonary disease (NTM-PD).

The company was quick to note that whilst SPR720 showed antimicrobial activity, “the interim analysis did not show sufficient separation from placebo.” Spero also noted that it plans to lay off 39% of its staff.

Following the announcement, the company’s stock was down by over 17% in premarket trading today. Spero reported that it has enough cash reserves to fund operations into mid-2026.

The Phase IIa trial (NCT05496374) enrolled 25 non-refractory patients with SPR720. The interim analysis of 16 patients showed no differentiation in antimicrobial effect from placebo evaluated using the rate of change in log10 colony forming units per millilitre (CFU/mL), the study’s primary endpoint. Potential dose-limiting “safety issues”, including three cases of Grade 3 hepatotoxicity, were seen in patients receiving 1,000mg orally once daily dose.

Spero plans to complete the data analysis of all 25 enrolled patients and “determine the next steps for the SPR720 program over the next several months.”

The company plans to funnel its resources into two of its antibiotic programmes – an oral carbapenem antibiotic, tebipenem HBr, and SPR206, a next-generation polymyxin. Spero has out licenced tebipenem HBr to GSK, with the latter having global marketing rights to the therapy, except in certain Asian countries. Spero has received $143.5m from GSK as part of the partnership to date and is eligible to receive up to $400m in additional milestone-based payments along with tiered royalties on sales.

The Phase III PIVOT-PO trial (NCT06059846) will compare oral tebipenem HBr with the two carbapenem antibiotics combination, intravenous imipenem and cilastatin, in hospitalised adult patients with complicated urinary tract infections (cUTI). The study is expected to recruit about 2,648 patients with cUTI, with enrolment planned for completion in the second half of 2025.

Spero plans to evaluate SPR206 as a treatment for multidrug-resistant (MDR) gram-negative pathogens in patients with hospital-acquired or ventilator-associated bacterial pneumonia (HABP/VABP). The company has received clearance from the US Food and Drug Administration (FDA) to start a Phase II trial. However, Spero noted that trial initiation is “contingent on availability of non-dilutive funding.”

Following the recent round of lay-offs, Spero joins the list of pharmaceutical companies such as Aerovate Therapeutics, Sage Therapeutics and Shattuck Labs that have fired workers in the l to funnelmoney into their clinical development pipelines.