# A new class of broad-spectrum antibacterials for treating MDR infections

> **NIH NIH R44** · CURZA INC · 2021 · $1,000,000

## Abstract

Project Summary
Cūrza is developing a new class of broad-spectrum antibiotic, with a focus on multidrug-resistant (MDR)
Enterobacteriaceae. The CZ-02 program is directed towards compounds that bind to a unique site on the
bacterial ribosome that is not targeted by existing antibiotics and is therefore not expected to encounter 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 genesis and progression of the CZ-02 program reflect a compelling argument in support of
natural products as a source of new therapeutic leads. The natural product identified as a lead has multiple
metabolic liabilities and minimal activity against Gram-positive and Gram-negative pathogens in vitro, and likely
in vivo. 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. The proposed Direct-to-Phase II project will ultimately develop a
new antibacterial drug candidate that is potent with broad spectrum activity, focusing on Gram-negative
pathogens that will be at the IND preparation stage.
Advancement of this antibacterial lead series for an initial UTI clinical indication will be accomplished by the
following aims. Aim 1 will optimize advanced leads for enhanced efficacy in infection models with MDR Gram-
negative pathogens. Curza’s proprietary model for producing potent and selective inhibitors of bacterial P-site
protein synthesis, in combination with numerous activity assays (biochemical, microbiological, in vitro ADME-
Tox), will be used to guide optimization efforts and eliminate compounds with potential safety liabilities. Aim 2
will define pharmacokinetics of optimized leads while identifying the maximum tolerated dose, which will guide
efficacy testing in thigh infection models to select 3 compounds for evaluation in urinary tract infection models.
A lead and backup drug candidate will be selected in Aim 3 by evaluation in UTI models of antibiotic-resistant
bacteria and the optimal dosing strategy will be determined from PKPD studies. Aim 4 will ultimately establish
the safety of the lead using non-GLP and GLP methods.

## Key facts

- **NIH application ID:** 10149944
- **Project number:** 5R44AI152665-02
- **Recipient organization:** CURZA INC
- **Principal Investigator:** Charles Testa
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,000,000
- **Award type:** 5
- **Project period:** 2020-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10149944

## Citation

> US National Institutes of Health, RePORTER application 10149944, A new class of broad-spectrum antibacterials for treating MDR infections (5R44AI152665-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10149944. Licensed CC0.

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