Fiscal Year 2019 Combat Readiness Medical Research Program Rapid Development and Translational Research Award Focus Area: Scalable solutions for wound care.

Background: In previous results from our research on burns, we have shown that a single 30 minute in the vein (i.e.,intravenous or iv) infusion of a protein fragment (peptide) that is given 4 hours after a severe burn limits injury progression (a possible reason why burns hurt for days) and speeds healing. Our first peptide, which is called cP12, is derived from a large protein called fibronectin (FN) that is normally found in blood and tissue.

From studies showing beneficial effects in animals, coupled with appropriate safety studies in animals, NeoMatrix Therapeutics was granted approval from the US Food and Drug Administration (FDA) in September 2017 to study the safety of the 30-minute iv administration of cP12 in a Clinical Safety Trial using normal healthy adult volunteers. This so-called Phase 1 Clinical Trial has been funded by the US Army’s Military Burn Research Program and was initiated in July 2019. The trial should be successfully completed by early 2020.

In addition, we have engineered another peptide from FN, which is called cNP8, that gives similar beneficial effects in burn wounds when given iv over 30 minutes beginning 24 hours after burn injury in pigs. Recently, cNP8 completed preclinical studies in animals (safety studies conducted in animals prior to safety studies in humans) that were funded by the US Army’s Joint Warfighter Medical Research Program.

Rationale and Objectives for the Current Study: In the proposed study, we will be able to complete all cNP8 work that is required by the FDA in order to advance our cNP8 studies into humans. This work requires rigidly controlled production of the cNP8 peptide and rigidly controlled manufacturing of the cNP8 drug product. In line with the FDA, our proposal also supports a detailed chemical analysis of the peptide ingredient and the final drug product as well as tracking their stability at room and refrigeration temperatures. In addition, we plan to study rapid 1-minute iv injections of cP12 or cNP8 at their optimal doses and times of administration. The results of these studies will be compared to results from similar studies using 30-minute iv infusions of peptides. This study will determine whether a faster iv injection therapy is as good as a 30-minute iv infusion therapy. There may be a need to give these peptides as quickly as possible in future war settings, where wounded Warriors cannot be quickly evacuated from the battlefield. Current safety studies in several animal models suggest that the risk of using 20-fold more peptide than approved is a minor transient reaction. For example, a 1-minute iv dose in animals that is 20 times the optimal therapeutic dose for use in humans causes some skin reddening and sneezing, which quickly stops without any treatment. Thus, rapid iv injections with much less peptide than used in the animal studies should cause little or no harmful reactions in humans.

Military Benefit: Historically, burn injuries account for 5%-20% of all injuries inflicted on American military personnel. Of these, 20% are considered severe or involve more than 20% of total body surface area. In addition, substantial burns occur in about 500,000 US civilians every year. Of these civilian burn victims, about 40,000 are sufficiently severe and/or extensive to warrant hospitalization. Furthermore 4,000 US civilian deaths, related to burns, occur yearly. The direct cost of burn care in the US is about $2 billion per year.

In this proposal, we plan to finish work that is required by the FDA in order to advance our cNP8 studies into humans. In addition, the animal work will determine whether the fast iv injection therapy works as well in burns as the slow 30-minute iv infusion therapy with the cP12 and cNP8 peptides. Such therapy would be transformative for burn care of wounded Warriors or civilians by reducing or eliminating immediate and/or long-term consequences of severe burns. These burn victims would be more likely to have shorter hospital stays, return to duty or work more quickly, and resume independent lives. Furthermore, the faster iv injection therapy would be best in a hazardous battlefield area where life may depend on things being completed faster than in normal situations.

The extremely stable, freeze-dried peptides come in small capped, sterile glass vials that can be easily dissolved in salt or buffer solutions for iv therapy, or mixed with soluble hyaluronan, which gels within a wound upon addition of a crosslinker.