Development of a Dual-Targeting ClpP Activating Antibiotic

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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.