Ceftibuten-Ledaborbactam Etzadroxil

Ceftibuten-Ledaborbactam Etzadroxil is designed for the treatment of patients with infections caused by drug-resistant Enterobacterales that are resistant to current standard-of-care oral and intravenous antibiotics, including fluoroquinolones, cephalosporins and carbapenems. Ledaborbactam etzadroxil (also known as VNRX-7145) is the orally bioavailable etzadroxil prodrug of ledaborbactam (also known as VNRX-5236), a broad-spectrum boronic acid beta-lactamase inhibitor (BLI). Ledaborbactam etzadroxil is being developed in combination with ceftibuten, a third-generation, orally-bioavailable cephalosporin antibiotic. In vitro and in vivo studies demonstrated that ledaborbactam restored the activity of ceftibuten against strains of Enterobacterales expressing extended spectrum beta-lactamases (ESBLs) and serine carbapenemases. The spectrum of inhibition includes Ambler class A ESBLs, class C cephalosporinases, and class A and D carbapenemases (KPC and OXA-48, respectively).

In July 2021, Venatorx announced positive top line results for its Phase 1 single ascending dose (SAD) and multiple ascending dose (MAD) clinical trial (ClinicalTrials.gov – NCT04243863) of ledaborbactam etzadroxil, the novel component of the investigational oral antibiotic combination product. In part 1, subjects received single ascending doses of ledaborbactam etzadroxil; in part 2, subjects received multiple escalating doses of ledaborbactam etzadroxil for 10 days. There were no serious adverse events, and ledaborbactam etzadroxil was well-tolerated up to the highest single or multiple doses administered. Ledaborbactam etzadroxil had excellent oral bioavailability, dose-proportional PK across the doses studied, and readily achieved efficacy exposure targets identified in non-clinical studies. Complete results from this study will be presented at an upcoming scientific meeting.

With these positive topline results in hand, Venatorx has continued the development of ceftibuten-ledaborbactam etzadroxil with a Phase 1 study to assess PK when ledaborbactam etzadroxil is dosed alone and in combination with ceftibuten. Additional ongoing Phase 1 studies include a renal impairment study and a food effect study to further evaluate the PK and inform dosing for upcoming Phase 3 clinical studies.

Cetibuten-ledaborbactam etzadroxil is an investigational drug and is not approved in any country for clinical use. For more information about ceftibuten-ledaborbactam etzadroxil, including open access to published posters and manuscripts, please visit: www.venatorx.com/publications.

This project has been funded in whole or in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN272201600029C.