Late-Stage Preclinical Development of Teixobactin to Treat Drug-Resistant Infections
Abstract
This project describes the late preclinical development of teixobactin, a new class of antibiotic to treat skin and lung infections and other serious infections in both military personnel and the general population. Teixobactin is very effective in animal models of infection, has not shown drug resistance, and has great promise for treating drug-resistant infections, as it kills the infecting bacteria through different mechanisms than current antibiotics. We have completed most of the safety and toxicology studies that are required before a drug can be tested in humans. As the next steps in drug development, we are required to develop methods to manufacture the compound under current Good Manufacturing Practice (cGMP) compliance and to determine safe maximum starting doses in human. The studies in this proposal will help to determine what dosages, dose frequency (e.g., once or twice daily, etc.), route of drug administration (e.g., injection, intravenous infusion, etc.), and how to manufacture and package the drug for delivery in a first-in-human clinical trial. Developing the manufacturing of the clinic-ready drug product is a main goal of this proposal. In addition, we propose an animal model study aimed at confirming the effective dose for humans. The Fiscal Year 2022 (FY22) Joint Warfighter Medical Research Program (JWMRP) Focus Area to be addressed by the proposed effort is the Endemic and Emerging Disease Threats: Therapeutic measures for infectious diseases, including combat wound care in austere and prolonged field care environments. Introducing a novel antibiotic into the clinic would be a great advance, considering the very few novel antibiotics approved since 2000, and the rise of antimicrobial resistance. Teixobactin’s attractive mode of action, lack of resistance, and activity against drug-resistant strains suggests that it may be able to address the clinical need of combating several serious infections faced by active-duty Service personnel, Veterans, and their families. Drug-resistant infections pose a particular threat for the military population due to environmental and occupational exposures unique to military service. These exposures may facilitate transmission of infections and thereby compromise Force health and operational readiness. This population remains at significant risk for infections caused by methicillin-resistant Staphylococcus aureus (MRSA) due to environmental and occupational exposures, such as combat associated deployments. Because infections can also interrupt training cycles and compromise operational readiness, effective treatment strategies for military populations are critically needed. For the general population, 2.8 million antibiotic-resistant infections occur in the U.S. every year, resulting in 35,000 fatalities. Teixobactin is a very potent antibiotic with a broad range of clinical applications including skin infections, bacterial pneumonia, tuberculosis, and anthrax. Since it is currently evaluated as an intravenously administered drug, its application will be for patients in the hospital setting. Teixobactin’s potential benefits include activity against serious bacterial infections, lack of resistance, and shorter treatment times with lower doses than required for current antibiotics. Although unlikely, the main risk is unacceptable side effect(s), which could prevent the administration of an effective dose. However, our animal studies to date suggest an effective dose of the compound can be safely delivered. The potential side effects (risks), if any, will be closely monitored in the clinic. The projected dosing schedule will be 7 to 10 days treatment with a daily intravenous infusion of 15 to 30 minutes duration. At the end of this project, we will be able to submit an Investigational New Drug application to the U.S. Food and Drug Administration (FDA) to obtain approval to test teixobactin in human clinical trials. The contributions of this proposal are essential,
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310376
Entities
People
- Dallas Hughes
Organizations
- NovoBiotic Pharmaceuticals
- United States Army