IND-enabling Studies of PM-208: A Novel Pre-hospital Anti-Shock Therapeutic

The direct and indirect effects of severe and prolonged tissue hypoxia due to hemorrhagic shock are leading causes of death following battlefield injuries. About 20% of all battlefield deaths are potentially survivable. Of these, most service members (84%) suffered hemorrhage and potentially could have been saved.  Resuscitation in the field is often seriously inadequate even in patients transported to local field hospitals for full resuscitation. Delays in evacuation in far-forward units may be hours to days. Time becomes critical. There remains a need for a more effective resuscitation medium for patients with severe hemorrhagic shock, especially in pre-hospital settings. For these lives to be saved better techniques and tools are required, first to address the loss of circulating blood and second to address the problems of reversible cellular and circulatory damage that unresuscitated shock can produce. It is the issue of secondary cellular and circulatory damage arising from shock that this proposal addresses. In a state of shock, the resultant energy deficit compromises the sodium pump resulting in sodium and water entering the cell causing swelling.  Tissue swelling after a period of shock significantly reduces the number of open capillaries and without specific intervention, may prevent the re-establishment of normal perfusion and the restoration of the cellular energy deficit even after the restoration of normal intravascular volume. Virginia Commonwealth University (VCU) and Perfusion Medical have addressed this with a strategy preventing metabolic cell swelling that occurs during tissue and cell ischemia by using cell impermeants. Using this approach over the last 15 years, the (VCU) laboratory has developed a next-generation LVR solution that, in pre-clinical models, is highly efficacious, stable, and outwardly safe. The USAMRDC has made a major investment funding the laboratory development of this solution at VCU.  This product, which we refer to hereafter as PM-208, can be used in conjunction with blood products, or given independently of blood, but is not a substitute for blood or plasma. PM-208 component increases tolerance to a low volume state seventeen-fold greater than an equivalent volume of LR, Hextend, or even fresh whole autologous blood in a highly robust swine hemorrhagic shock survival model. Survival to 24 hours increases from 0% in the LR or whole blood volume controls to 100% with PM-208 alone. Maximum survival tested to date is 7 days so far with PM-208. Perfusion Medical was established to bring PM-208 to market. The company has raised more than $1 million, completed the pre-IND process with the FDA and begun manufacturing in a GMP environment. The funding requested in this proposal will allow the company to achieve a key regulatory milestone, IND filing, and advance development of a version of the drug designed for military field use.