# Development of a Dual-Targeting ClpP Activating Antibiotic

> **NIH NIH R44** · ARIETIS · 2024 · $999,619

## Abstract

The World Health Organization has declared that antimicrobial resistance is one of the biggest threats to global
health. It was estimated that by 2050, deaths due to drug resistant bacteria will exceed those caused by cancer.
The goal of this project is to develop a new ureadepsipeptide antibiotic (UDEP) to treat infections caused by
Gram-positive pathogens, such as bacteremia, pneumonia, endocarditis, and prosthetic joint infections. UDEPs
have a unique mechanism of action – they kill bacteria by causing cells to digest their own proteins. This
mechanism enables activity against non-growing and dormant cells of bacteria that traditional antibiotics cannot
kill. Thus, UDEPs have the potential to fill a large and unmet medical need for biofilm-related and difficult to treat
infections. UDEP target what the CDC classifies as serious and concerning drug-resistant threats including
Methicillin-Resistant Staphylococcus aureus (MRSA), Vancomycin-Resistant Enterococcus (VRE), Drug-
Resistant Streptococcus pneumoniae, Vancomycin-Resistant Staphylococcus aureus, Erythromycin-Resistant
Group A Streptococcus, and Clindamycin-Resistant Group B Streptococcus. The goal of this project is to
determine if a new UDEP called 5192, which was specifically designed to have a low frequency of resistance, is
a suitable candidate to enter investigational new drug enabling non-clinical development so it can be tested in
human trials in the future.

## Key facts

- **NIH application ID:** 10915576
- **Project number:** 5R44AI179382-02
- **Recipient organization:** ARIETIS
- **Principal Investigator:** Michael LaFleur
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $999,619
- **Award type:** 5
- **Project period:** 2023-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10915576

## Citation

> US National Institutes of Health, RePORTER application 10915576, Development of a Dual-Targeting ClpP Activating Antibiotic (5R44AI179382-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10915576. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*