Rationale and Objective: Wounds acquired in combat and on the battlefield are accompanied by a significant risk of infection and are increasingly caused by multidrug-resistant organisms (MDROs), which have limited treatment options. Furthermore, once established, the opportunity for cross-contamination of MDRO infections between patients in military trauma settings is significant. Thus, there is a real need for new treatment options for MDROs and other infections to reduce combat-related or trauma-induced wound infection morbidity and mortality. We have previously demonstrated that a novel nanoemulsion, NB-201, is a safe and stable compound that, when applied topically, greatly reduces MDRO infection against methicillin-resistant Staphylococcus aureus (MRSA) in skin abrasion wounds in mice and split-thickness wounds in pigs, and against P. aeruginosa burn wounds in rats. The objective of this study is to complete rigorous preclinical testing of this compound such that it can be advanced to the Food and Drug Administration (FDA) approval process.

FY14 MID-ARA Focus Areas Addressed: This proposal addresses the third FY14 MID-ARA Focus Area to develop and preclinically test novel classes of materials with potential therapeutic benefit for wound infection. We propose to conduct further testing on the nanoemulsion NB-201 to complete the preclinical safety and toxicity studies sufficient to support an Investigational New Drug/Investigational Device Exemption (IND/IDE) application.

How Proposed Research Impacts Focus Areas: The proposed study directly impacts the above Focus Area, first, because it conducts further in vitro and in vivo studies on NB-201, a compound that has already been shown to be highly effective against MRSA in abrasion and split-thickness wounds in mice and pigs, and against P. aeruginosa in burn wounds. These studies will greatly augment our understanding of the potential range of activity of NB-201 across various classes of microorganisms, including fungi, at different concentrations of the active ingredient BZK (benzalkonium chloride). In addition, this proposal also completes all studies required by the FDA prior to IND submission, including the manufacture and testing of current Good Manufacturing Practice (cGMP) materials. As a result, the work described in this proposal will greatly expedite the development, testing, and regulatory approval of NB-201.

Potential Clinical Applications, Benefits, and Risks: NB-201 is a topically applied nanoemulsion with antimicrobial activity against at least two MDROs, MRSA and P. aeruginosa. Furthermore, the mechanism of action is thought to involve disruption of the cell wall of microorganisms by the nanoemulsion, as well as antimicrobial activity by BZK. Because this is not a targeted approach to killing specific bacteria, it is expected that this approach will have broad applicability as an antimicrobial, and if so, will be a novel and important contribution to the arsenal of drugs capable of controlling microbial infections.

Benefits to Military, Department of Veterans Affairs (VA), and Civilian Patient Populations: If successful, NB-201 will be developed as a stable and safe, topically applied microbial. Because it is likely to be both stable and safe, it may be possible for individual Soldiers to carry NB-201 in battle, for use for themselves or their comrades on the battlefield. It is also likely to be used by health professionals during transport of injured Soldiers, and at VA hospital facilities to further control infections in individual patients, and across the hospital as an institute. NB-201 is likely to be similarly useful in the civilian setting to control infections in individuals and in hospitals.

Projected Time to Achieve Patient-Related Outcome: Assuming that funding for this proposal begins in the second quarter of 2014, we estimate that the final specific aim, submission of the IND/IDE documents to the FDA, will occur in the last quarter of 2016. This would permit the initiation of Phase 1 Clinical Trials to be initiated as early as 2017, with patient-related outcome data available in 2018.