Ceftibuten/VNRX-7145

Ceftibuten/VNRX-7145 is designed for the treatment of patients with infections caused by multi-drug resistant (MDR) gram-negative pathogens that are resistant to current standard-of-care oral and intravenous antibiotics, including fluoroquinolones, cephalosporins and carbapenems. VNRX-7145 is the orally bioavailable etzadroxil prodrug of VNRX-5236, a broad-spectrum boronic acid beta-lactamase inhibitor (BLI). VNRX-7145 is being developed in combination with ceftibuten, a third-generation, orally-bioavailable cephalosporin antibiotic. In vitro and in vivo studies demonstrated that VNRX-5236 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 VNRX-7145, a novel component of the investigational oral antibiotic combination product. The Phase 1 study was a 2-part, first-in-human dose-ranging study to evaluate the safety and pharmacokinetics (PK) of escalating oral doses of VNRX-7145. In part 1, subjects received single ascending doses of VNRX-7145; in part 2, subjects received multiple escalating doses of VNRX-7145 for 10 days. There were no serious adverse events, and VNRX-7145 was well-tolerated up to the highest single or multiple doses administered. VNRX-7145 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 is continuing the development of VNRX-7145 with a Phase 1 drug-drug interaction (DDI) study (ClinicalTrials.gov – NCT04877379), which will provide an initial assessment of the safety and PK of single and multiple doses of VNRX-7145 and ceftibuten, the selected beta-lactam partner, when co-administered. Top line results are expected in the fourth quarter 2021.

VNRX-7145 alone and in combination with ceftibuten is an investigational drug and is not approved in any country for clinical use. For more information about VNRX-7145, 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.