Lead identification of oral ftsz inhibitors for the treatment of clostridioides difficile infections(CDI)

The National Institute of Allergy and Infectious Diseases awarded Taxis Pharmaceuticals Inc. $294,729 on August 12, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to identify lead oral FtsZ inhibitors for treating Clostridioides difficile infections.

Taxis will evaluate a proprietary benzamide chemical class targeting FtsZ, an essential bacterial protein, to develop a narrow-spectrum oral therapeutic for CDI where existing first-line therapies fail. The work will assess solubility and stability profiles at gut pH, cecum exposure at 24 hours, efficacy in clearing infections and preventing CDI recurrence in mouse models, and therapeutic index. The recipient drew on experience developing TXA709, an FtsZ clinical candidate for MRSA and vancomycin-resistant enterococci, to inform this Phase I Small Business Innovation Research effort.

Performance occurs at Monmouth Junction, New Brunswick Township, New Jersey, with an ultimate completion date of July 31, 2028. The award is structured as a Project Grant, the assistance type for SBIR Phase I awards from NIAID.

Abstract

Clostridioides difficile (C. Difficile) is the leading cause of healthcare-associated infection in the US and considered an urgent threat by the centers for disease control and prevention (CDC). Only three antibiotics, metronidazole, vancomycin and fidaxomicin, are FDA-approved for the treatment of C. Difficile infection (CDI), but these therapies still suffer from high treatment failure and recurrence. Therefore, new chemical entities to treat CDI are critically needed. This sbir phase I proposal presents a significant opportunity to develop a narrow- spectrum oral therapeutic for CDI, where existing first-line therapies fail. Our proprietary chemical class targets ftsz, an essential bacterial protein, and shows excellent in vitro potency against multiple toxigenic and hypervirulent C. Difficile clinical isolates. This class is composed of benzamide sub-series that boast outstanding characteristics appropriate for C. Difficile targeting antibiotics such as non-toxicity towards mammalian colon cells, low caco-2 permeability indicating high GUT localization, and lack of any deleterious effect on important representative members of the normal GUT microbiota. This sbir phase I application aims to identify the best sub-series as well as a backup sub-series by evaluating four key parameters: (I) their solubility and stability profile specially at the GUT PH; (II) their cecum exposure at 24 H; (III) their ability to clear the infections and protection of mice from CDI recurrence; and finally (IV) their therapeutic index (efficacious dose/daily dose). Drawing on insights and experience from developing our ftsz clinical candidate, TXA709, for treating methicillin-resistant staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE), we believe this sbir grant will bolster our efforts to deliver first-line oral treatment for untreatable CDI. 1