# A new class of antibiotic to address Antimicrobial Resistance

> **NIH NIH R44** · CURZA INC · 2024 · $999,998

## Abstract

Project Summary
Cūrza is developing a new class of broad-spectrum antibiotics, focused on multidrug-resistant (MDR) Gram-
negative pathogens. The CZ-02 program is directed towards compounds that bind to a unique site on the
bacterial ribosome that is not targeted by approved antibiotics and have not encountered cross-resistance to
other antibiotics used clinically. Inspired by a natural product identified as a lead for Mycobacterium tuberculosis
(Mtb), analogs have been developed that selectively inhibit bacterial protein synthesis, with little effect on
mammalian protein synthesis, through a binding interaction with the ribosome at a heretofore un-drugged site.
The natural product that inspired CZ-02s has multiple metabolic liabilities and lacks activity against Gram-
negative pathogens. However, after re-engineering the natural product’s minimum pharmacophore responsible
for activity into new chemical matter the resulting compounds are metabolically stable, exhibit exquisite selectivity
and potency for bacterial protein synthesis and are efficacious against MDR pathogens in vitro and in vivo; all
while displaying a lack of cytotoxicity toward mammalian cells and sparing mitochondrial function. The proposed
SBIR project will ultimately deliver a new antibiotic candidate that is potent with broad spectrum activity and
efficacy, focusing on Gram-negative pathogens that will be at the GLP toxicology stage.
This Direct Phase II project will advance the CZ-02 program by the following aims. Aim 1 will optimize the lead
series to improve activity against Pseudomonas aeruginosa and Acinetobacter baumannii while maintaining
coverage of Enterobacterales and Gram-positive pathogens. Rigorous microbiological and biochemical
evaluation along with profiling of absorption, distribution, metabolism, excretion and toxicity (ADME-Tox) will
guide optimization efforts. Aim 2 will use in vivo pharmacokinetic (PK) evaluation to guide optimization along with
maximum tolerated dose (MTD) determination to guide in vivo efficacy initially in mouse septicemia models to
select lead compounds for evaluation in pneumonia models of P. aeruginosa and/or A. baumannii for down-
selection to a single lead candidate. Aim 3 will provide scale-up chemistry to support in vivo studies. Aim 4 has
sophisticated PK/pharmacodynamic (PD) profiling to establish the PD driver of efficacy and definition of the
optimal dosing regimen in pneumonia models.
At the culmination of the project, a lead compound will be ready for non-GLP toxicology and subsequent IND-
enabling studies to ultimately deliver a new antibiotic from a novel class targeting Gram-negative pathogens.

## Key facts

- **NIH application ID:** 10920863
- **Project number:** 1R44AI184155-01
- **Recipient organization:** CURZA INC
- **Principal Investigator:** Charles Testa
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $999,998
- **Award type:** 1
- **Project period:** 2024-05-01 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10920863

## Citation

> US National Institutes of Health, RePORTER application 10920863, A new class of antibiotic to address Antimicrobial Resistance (1R44AI184155-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10920863. Licensed CC0.

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