Engineering Batch Manufacturing of a Field-deployable Synthetic Platelet Surrogate (SynthoPlate) for Hemorrhage Control

Combat-associated traumatic hemorrhage remains the primary cause of 'preventable mortality' on the battlefield for our military. In fact, traumatic hemorrhage is one of the leading causes of death in the age group 1-46. Early resuscitation with whole blood or components mitigates hemorrhage and shock, which reduces mortality, but availability remains a challenge in austere settings. This is particularly true for platelets, which are the primary cells that stop bleeding. Currently, platelets are stored under agitation at room temperature and have a very short shelf-life of ~5 days due to high risks of contamination and loss of function. Furthermore, platelets are donor-dependent and thus suffer from constant shortage. Altogether, these limitations in platelet products significantly limit their on-demand use in battlefield settings. Donor-independent therapeutic technologies that provide platelet-mimicking hemostatic functions while allowing large-scale manufacture, long-term storage, and ease of portability for on demand use at point-of-injury/point-of-care (POI/POC) can provide significant logistical and therapeutic benefit for rapid and early hemorrhage control to save lives. To this end, Haima Therapeutics is developing SynthoPlate (SP), an innovative fully synthetic platelet-inspired hemostatic nanotechnology. We have demonstrated that SP is amenable to scalable manufacture and stable for long time-periods (>12 months) as a lyophilized powder in a small vial under various storage temperatures. Furthermore, SP’s safety and hemostatic efficacy have been demonstrated in vivo in several animal models of bleeding (e.g., tail transection in thrombocytopenic mice, liver laceration in rats, kidney incision after dilutional coagulopathy in rabbits, and polytrauma hemorrhage in rabbits). No signs of toxicity in the therapeutic dose range were observed. Lastly, a >200x therapeutic index was established in dose-range finding toxicology studies in rats, rabbits, and dogs. Building on this, in this DARPA SBIR, Haima is proposing to manufacture the Engineering Batch of SP under GMP-capable conditions to study its stability and to support investigational new drug (IND)-enabling preclinical studies (funded through a separate DARPA SBIR). This will enable Haima to file an IND application with the FDA to initiate early clinical trials. It is envisioned that SP will be used as a ‘stand-alone’ as well as an ‘adjunctive’ treatment of hemorrhage in various clinical scenarios.