SPR-206

Spero’s SPR729 is a prodrug that converts into an active form that targets ATPase site of DNA gyrase B in mycobacteria. Image credit: Lemonsoup14 / Shutterstock. 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. Antibiotic development has seen mixed results in recent months. Last week, the US FDA approved Iterum Therapeutics’s Orlynvah (sulopenem etzadroxil and probenecid) for treating uncomplicated UTIs (uUTIs) caused by E. coli, Klebsiella pneumoniae or Proteus mirabilis in adult women who have limited or no alternative antibacterial treatment options. Whilst AN2 Therapeutics suspended development for its lead antibiotic, epetraborole, after it failed to show efficacy in Phase II/III trial (NCT05327803). AN2 was evaluating epetraborole as a treatment for refractory mycobacterium avium complex (MAC) lung disease. 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.

iStock, simplehappyart Following disappointing results for an antibiotic candidate whose development program is now being suspended, Spero Therapeutics is looking to extend its cash runway while it focuses on other assets in its pipeline. As part of a restructuring following the suspension of its development program for an antibiotic candidate, Spero Therapeutics will lay off about 39% of its workforce, the company announced Oct. 29. The clinical-stage biopharma expects to mostly complete the cuts by end of the year, according to an Oct. 29 SEC filing . As of Dec. 31, Spero had 46 employees, 30 of whom were mostly handling R&D activities, as noted in a March 13 SEC filing . If the Cambridge, Massachusetts, business has the same number of employees now, the cuts could affect about 18 people. Regarding its antibiotic candidate, Spero shared that an interim analysis of the Phase IIa study of SPR720, a treatment being investigated for nontuberculous mycobacterial pulmonary disease, did not meet the primary endpoint. The company noted that while there was antimicrobial activity associated with SPR720, the analysis did not show sufficient separation from placebo. In addition, the data highlighted potential dose-limiting safety issues in subjects dosed at 1,000 milligrams orally once daily, including three cases of reversible grade 3 hepatotoxicity. Spero’s restructuring is expected to extend the company’s cash runway and support operations into mid-2026, according to the announcement. During this time, the biopharma will focus on advancing tebipenem HBr in an ongoing global Phase III trial and preparing for a Phase II trial for SPR206, contingent on continued nondilutive funding. Tebipenem HBr is an oral carbapenem antibiotic meant to treat complicated urinary tract infections. SPR206 is an intravenously administered next-generation polymyxin that has shown antibiotic activity against multidrug-resistant Gram-negative pathogens, according to the company. Tebipenem HBr is tied to a previous layoff at Spero. In 2022, the company cut about 75% of its workforce as part of a restructuring ahead of an expected FDA rejection of the antibiotic. According to a May 3, 2022, SEC filing , those layoffs reduced Spero’s full-time staff from 146 to 35 employees. The FDA did reject the drug , and in September 2022, GlaxoSmithKline announced it would license tebipenem HBr as part of a $66 million licensing deal .