IND-Enablement of Kinocidin Gamma-RP-1 for MDR Gram-Negative Infections
Abstract
U.S. military personnel often face increased risks of infection by life-threatening microbes that are no longer susceptible to traditional antibiotics. Moreover, conditions of warfare and combat injury pose many additional risks of infection due to organisms that are resistant to conventional antibiotics and for which vaccines are not available. Additionally, U.S. warfighters face risks of severe or penetrating wound injuries, burns, suboptimal hygiene, chronic sleep dysregulation, heightened physical and/or emotional stress, and suboptimal nutrition, which further reduce immune defenses and increase vulnerability to these dangerous and antibiotic-resistant infections. The overarching priority and principal goal of this project is to rapidly accelerate novel anti-infective technology to protect U.S. warfighters, military, and ultimately civilian personnel from resistant and emerging pathogens. Application of such novel anti-infective agents that also amplify the immune system would be a breakthrough in protecting military and civilian populations. The kinocidin peptide technology is designed to achieve these very goals. This novel anti-infective technology is designed from natural proteins released by human blood platelets at wound sites. Here, these molecules exert strong antimicrobial activities, enhance immune defense, and promote wound healing. Collectively, these features make the lead candidate molecule gamma-RP-1 a state-of-the-art technology of especially high relevance to U.S. military. Importantly, this new type of anti-infective technology overcomes many of the historical limitations of classical antimicrobial peptides, which have encountered issues of stability in blood, disabling toxicity, and cost-prohibitive manufacturing. The current program follows a logical, strategic, and highly efficient plan to accelerate the preclinical development of gamma-RP-1 and lays ideal groundwork for immediate follow-on clinical trials. The lead candidate molecule, gamma-RP-1, will first be optimized for efficient and commercially scalable manufacturing and qualified as an active drug product. Next, it will be validated for efficacy against Acinetobacter baumannii, a model for multidrug-resistant Gram-negative bacteria of utmost priority in U.S. military wounded and injured. To do so, gamma-RP-1 product will be tested in an experimental model of infection that mimics life-threatening infection in humans. Then, it will be studied to ensure it is safe and effective in two distinct animal models. Based on results from this thorough body of preclinical data, we will accelerate preparations for regulatory guidance in anticipation of advancement to Phase I clinical trials in humans. This technology reflects a breakthrough in anti-infective discovery. A crucial next step is to perform preclinical studies as detailed to ideally position it to accelerate to clinical trials and benefit U.S. warfighters, military defense personnel, and ultimately civilian populations. The gamma-RP-1 molecule has remarkably strong efficacy against even the most dangerous pathogens in human blood, favorable safety profiles, an ability to increase immune defenses, and can restore or enhance the effectiveness of traditional antibiotics. Hence, speeding the preclinical development of this exciting anti-infective technology is an urgent and high-priority to protect U.S. military personnel and benefit the civilian population as well. These goals align to the Joint Warfighter Medical Research Program objectives: (i) development of novel medical countermeasures and innovative treatment approaches for MDR organisms in combat wound infections and (ii) development of treatment options for infectious diseases potentially leading to U.S. Food and Drug Administration (FDA)-licensable, broadly active therapeutics vs. multiple disease threats.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010133
Entities
People
- Michael Yeaman
Organizations
- Harbor–UCLA Medical Center
- United States Army