A new class of broad-spectrum antibacterial agents to treat multi-drug resistant pathogens
Active Project Grant Awarded Last action
- Award ID
- R44AI170297
- Recipient
-
Curza Inc. UEI VGN5BH7K3DN9
- Awarding agency
-
National Institute of Allergy and Infectious Diseases
National Institutes of Health, Department of Health and Human Services
- Obligated
- $5,858,436
Award facts
- Assistance listing
- 93.855 Allergy and Infectious Diseases Research
- Completion date 83% complete
- Originally
- Place of performance
- Emigration Canyon, UT 84108, USA
Award details come from USAspending.gov.
Description
- Abstract
- Curza is developing the CZ-02 platform of broad-spectrum antibiotics as a new class focusing on multidrug- resistant (MDR) gram-negative pathogens that will also be efficacious against gram-positive bacteria. CZ-02 antibacterials bind to a unique site on the bacterial ribosome that is not targeted by antibiotics available clinically which is expected to limit cross-resistance to other antibiotics. The initiation and subsequent development of the CZ-02 program represents a strong example for revisiting the use of natural products in drug discovery which has fallen out of favor in pharma. CZ-02S were inspired by the natural product amicetin which selectively inhibits bacterial protein synthesis but suffers from limited antibacterial activity and poor drug-like properties. Careful engineering of the natural product has produced CZ-02S with exquisite selectivity for bacterial protein synthesis, potent antibacterial activity and excellent drug-like properties that have demonstrated efficacy against MDR pathogens in multiple animal models of infection while sparing mammalian cells from cytotoxicity. The goal of this direct-to-phase II project is to develop a new antibacterial drug candidate that covers gram- negative pathogens found among enterobacterales and the non-fermenters acinetobacter baumanni and pseudomonas aeruginosa as well as gram-positive pathogens. The initial clinical indication will be for treating urinary tract infections (UTIS), with other indications to follow (e.g. complicated intra-abdominal infections, pneumonia, bacteremia). At the conclusion of this phase II sbir will be a pre-clinical development candidate that is potent with broad spectrum activity that will be ready for chemistry, manufacturing and controls (CMC) and toxicology/safety pharmacology under good laboratory practices (GLP). Advancement of this antibacterial lead series will be accomplished by the following aims. Aim 1 will expand the spectrum of activity for advanced leads that have shown efficacy in UTI animal 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 a battery of biological/biochemical activity assays (biochemical, microbiological, in vitro adme-TOX), will be used for chemistry efforts to ensure compounds retain activity while expanding the spectrum of addressable pathogens to include a. Baumannii and P. Aeruginosa. Aim 2 will define pharmacokinetics (PK) while identifying the maximum tolerated dose and confirming efficacy by testing in thigh infection models to select CZ-02S for evaluation in UTI models. A lead and backup drug candidate will be selected in aim 3 by evaluation in UTI models of antibiotic-resistant bacteria followed by non-GLP toxicology in rats to nominate a lead and backup. Aim 4 will scale-up production (non-GLP) to support in vivo studies while aim 5 will establish the optimal dosing strategy from PK/pharmacodynamic (PD) studies.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $0 | |
| Amendment | $858,436 | |
| Amendment | $1,000,000 | |
| Amendment | $1,000,000 | |
| Amendment | $0 | |
| Amendment | $0 | |
| Amendment | $1,000,000 | |
| Amendment | $1,000,000 | |
| Original award | $1,000,000 |
Quick answers
Who received award R44AI170297?
R44AI170297 was awarded to Curza Inc. by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on July 21, 2023.
How much is award R44AI170297 worth?
$5,858,436 has been obligated on R44AI170297.
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