There is need for an artificial oxygen (O2) carrier to substitute for stored blood products, which at times are unavailable (pre-hospital care, austere environments, resource-limited countries), undesirable (risk of immune response), or in short supply to meet demand (mass casualty event). Moreover, transfusion of a crystalloid or colloid solution alone will lead to dilutional deficiencies of blood components such as red blood cells (RBCs), which are critical for delivering oxygen (O2) to the various tissues. KaloCyte's focus is to develop ErythroMer (EM), a lyophilized, bio-inspired, artificial RBC, which will transform how patients who need a transfusion are treated when stored RBCs or whole blood are not an option. Previous oxygen carrier products have had two major design flaws preventing them from mimicking RBC physiology: (1) inability to appropriately release O2 to tissues after capture in the lungs and (2) sequestration of nitric oxide (NO) resulting in vasoconstriction. EM is designed to not only carry O2 but also surmount the barriers encountered by prior oxygen carriers (intended as red blood cell substitutes). EM accomplishes this by emulating physiologic RBC O2 capture and delivery along with benign interaction with the vasculature. These key bio-inspired design features differentiate EM from previous attempts. Moreover, EM is designed for sterile lyophilization and so, is amenable to facile, rapid reconstitution after extended dry storage under ambient conditions. EM offers a pragmatic approach to a complex need and is designed for cost-effective production at scale. Our prototype has passed rigorous initial ex vivo and in vivo proof of concept testing. KaloCyte was founded so that we may translate EM innovations into a pragmatic therapeutic and as well as realize the commercial potential of a disruptive introduction into transfusion medicine. Our project goals are to enable rapid, facile reconstitution and establish the optimal colloid (albumin and freeze-dried plasma), and crystalloid (normal saline, lactated ringers, PlasmaLyte A) ratios for EM resuspension, while not disrupting the osmolality and oncotic pressure of blood. EM intellectual property is robust and secured by KaloCyte, which is supported by a solid research team, our CEO with a strong therapeutic industry background and scientific advisors, with experience in hemoglobin-based oxygen carrier development, lyophilization, transfusion medicine, hemorrhage & resuscitation, pre-clinical development and trial design. SBIR funding will enable KaloCyte to critical pre-clinical development in EM production and initiate groundwork required for IND authorization. Of note, our initial studies and the approach herein meet published FDA expectations for blood substitutes. Given the significant need and market potential we have hemorrhagic shock as the first indication for FDA approval. Following a successful trial for hemorrhagic shock, we would expand EM into other settings and exploit the design to extend efficacies beyond that of stored blood.
Public Health Relevance Statement: PROJECT NARRATIVE There is need for an artificial oxygen carrier to care for anemic and bleeding patients in settings where stored red blood cells or whole blood is unavailable, undesirable or in short supply. To address this critical need, KaloCyte was founded to develop ErythroMer (EM), a first-in-class, lyophilized, bio-inspired, artificial red blood cell, into a pragmatic therapeutic for hemorrhagic shock. This proposal will support that effort.
Project Terms: Address; Adverse effects; Affinity; Albumins; American; Authorization documentation; base; Benign; Blood; Blood Pressure; blood product; Blood Substitutes; Caring; Cell physiology; Characteristics; Clinical Trials Design; Collaborations; Colloids; Complex; cost effective; Country; crystalloid; Department of Defense; design; Development; Environment; Erythrocytes; Event; expectation; experience; Freeze Drying; Funding; Goals; Grant; Hemoglobin; Hemorrhage; Hemorrhagic Shock; Home environment; Hospitals; Human; human study; Immune response; in vivo; Individual; Industry; innovation; Intellectual Property; Lactated Ringer's Solution; Life; Liquid substance; Lung; mass casualty; nanoencapsulated; Nitric Oxide; Normal saline; operation; Osmolalities; Osmolar Concentration; Oxygen; Patients; Phase; Physiological; Plasma; Plasmalyte A; Pre-hospitalization care; preclinical development; pressure; prevent; preventable death; Process; Production; prototype; Publishing; rapid technique; reconstitution; Red Cross; Research; Resources; Resuscitation; Risk; Secure; Small Business Innovation Research Grant; Solid; Sterility; Testing; Therapeutic; Time; Tissues; Training; Transfusion; transfusion medicine; Translating; Trauma; Vascular blood supply; vasoconstriction; Water; Whole Blood
