Discovery

Cūrza backed by NIAID award for novel ribosomal inhibitor to combat multidrug-resistant infections

Cūrza backed by NIAID award for novel ribosomal inhibitor to combat multidrug-resistant infections

Curza Inc, a Salt Lake City-based antibiotic developer, has received a USD 1 million NIAID SBIR award to advance CZ-02, a novel class of oral antibiotics targeting multidrug-resistant Gram-negative pathogens — a bacterial threat for which no new oral antibiotic class has reached patients in over four decades.

The R44 Direct Phase II grant, administered through the National Institute of Allergy and Infectious Diseases, funds late preclinical development of CZ-02 compounds designed to inhibit bacterial protein synthesis at a ribosomal binding site not targeted by any approved antibiotic. The natural product-inspired scaffold has been re-engineered to overcome the metabolic liabilities of its parent compound and to achieve activity against Gram-negative organisms, a class historically difficult to penetrate due to their outer membrane barrier. Preclinical data reported by the company indicate potency against MDR strains of Klebsiella pneumoniae and Escherichia coli in vitro and in vivo, with selectivity for bacterial over mammalian ribosomes and no observed mitochondrial toxicity.

The funded work, led by principal investigator Charles A. Testa, pursues two parallel strategies to achieve oral bioavailability: formulation optimization and medicinal chemistry modification of physicochemical properties. In vivo pharmacokinetic studies and mouse models of septicemia, complicated urinary tract infection, and acute pyelonephritis will guide lead selection, with pharmacokinetic/pharmacodynamic profiling to define dosing parameters. The project is designed to deliver a single lead candidate ready for non-GLP toxicology and subsequent IND-enabling studies by grant completion in June 2027.

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The antimicrobial resistance space has attracted sustained NIH investment, but orally bioavailable agents active against MDR Gram-negatives remain a significant unmet need. Most recently approved Gram-negative antibiotics — including cefiderocol and imipenem-cilastatin-relebactam — are intravenous agents, limiting their utility in outpatient settings. Curza's focus on oral delivery for cUTI and pyelonephritis indications addresses a clinically relevant gap, as these infections are among the most common drivers of MDR Gram-negative morbidity in community and hospital settings.


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