Development of oxepanoprolinamide antibiotics for the treatment of complicated urinary tract infections

The National Institute of Allergy and Infectious Diseases awarded Kinvard Bio, Inc. $314,363 on August 3, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to develop oxepanoprolinamide antibiotics for the treatment of complicated urinary tract infections.

Kinvard Bio is conducting microbiological profiling of oxepanoprolinamide (OPP) candidates, a new class of ribosome-binding antibiotics designed to treat gram-negative infections resistant to standard-of-care therapies. The OPPs are derived from the lincosamide class but optimized to extend spectrum to gram-negative pathogens responsible for complicated urinary tract infections, with binding affinity approximately 300-fold greater than clindamycin. Preliminary data indicate high likelihood of oral bioavailability, supporting potential for intravenous with oral step-down treatment options and outpatient use.

Work is performed in Flourtown, Pennsylvania. The period of performance extends from August 3, 2026 through July 31, 2027. This is a Phase I Small Business Innovation Research award, an assistance type reflecting Kinvard Bio's status as a domestic small business.

Abstract

Complicated urinary tract infections (cuti) are highly prevalent, principally gram-negative, infections worldwide that can manifest in life-threatening complications if left untreated. In an ever-increasing proportion of these infections, the failure of standard-of-care (SOC) therapy centered on beta-lactams/beta-lactam inhibitors (BL/BLI), fluoroquinolones, and trimethoprim-sulfamethoxazole has left healthcare providers with limited options for outpatient treatment or step-down from parenteral agents. To reduce reliance on last-line carbapenem antibiotics, as well as to enable outpatient treatment and earlier hospital discharges, there is a significant need for a non-carbapenem, non-BL/BLI, intravenous with oral step-down therapeutic option for the treatment of cutis. To address this critical yet unmet need, kinvard BIO is advancing a new class of highly potent ribosome-binding antibiotics termed the oxepanoprolinamides (opps). The opps are inspired by the lincosamide class of antibiotics, of which clindamycin (CLI) is the most recently approved (1970, FDA) and most widely known. While the lincosamides are primarily useful as gram-positive facing agents (and therefore less applicable to cuti), the opps have been optimized to dramatically improve engagement of the bacterial ribosome (≥300-fold improved binding compared to CLI). This enhancement for the first time extends the spectrum of activity of the class to include the gram-negative pathogens responsible for cuti, with potent activity against cross-resistant strains. Furthermore, preliminary caco-2 studies and canine pharmacokinetic analyses suggest that the opps have a high likelihood of oral bioavailability, following precedent from their progenitor CLI, which has 88% oral bioavailability in humans. In this project, a thorough microbiological profiling of ten OPP antibiotics against resistant cuti isolates will be conducted, from which three finalist opps will be selected for further profiling in preliminary in vitro adme and in vivo pharmacokinetic studies. The three finalist opps will then be compared in proof-of-concept murine models of infection (neutropenic thigh infection model and ascending UTI model) using a uropathogenic escherichia coli isolate, from which one lead OPP compound will be selected for further studies to establish a full dose response profile. Through this project, we plan to progress at least one lead OPP compound toward candidate selection and preclinical development work.