ErythroMer: Nanoscale Bio-Synthetic Red Cell Substitute

PROJECT SUMMARY There is need for an artificial oxygenOcarrier to substitute for banked blood in settings wherestored blood is unavailablepre hospital care transportaustere environmentsundeveloped countriesorundesirabletransfusion risk exceeds benefitTo address this needwe developedErythroMerEMa first inclass nano cyte blood substituteEM is a deformablecross linked polymeric nanoparticle that incorporates high per particle payloads of hemoglobinHbOurartificial celldesign has yielded a prototype that emulates RBC physiology in all key respects and represents a potentially disruptive introduction into Transfusion MedicineTo dateefforts to develop Hb based oxygen carriersHBOCshave failedbecause of design flaws which do not preserve physiologic interactions of Hb withOthey capture Oin lungsbut do not release Oeffectively to tissueandnitric oxideNOthey trap NOcausing vasoconstrictionThe EM design surmounts these weaknesses byencapsulating Hbcontrolling Ocapture release with a novelDPG shuttleDPG is the major heterotropic effector for Hb and diminishes Oaffinityattenuating NO uptake through shell propertiesandretarding metHb formation by co packaging a reduction systemMoreoverEM is designed for sterile lyophilization and sois amenable to facile reconstitution after extended dry storage under ambient conditionsEM offers a pragmatic approach to a complex need and is designed for cost effective production at scaleOur prototype has passed rigorous initial ex vivo and in vivoproof of concepttestingWe founded KaloCyte so that we may translate ErythroMer innovations into a pragmatic therapeutic and as well as realize the commercial potential of a disruptive introduction into transfusion medicineOur project goals are to scale up reliable EM productionperform pharmacokinetic studiesinitiate toxicity screening and affirm efficacy in a robust animal model of hemorrhagic shock resuscitationErythroMer intellectual property is robust and secured by KaloCytewhich has been supported by robust entrepreneurincubator programs that have afforded business and regulatory expertiseinitial space and administrative supportSTTR funding will enable KaloCyte to transition EM production from researchto pilot scalePhase Iand initiate groundwork required for IND authorizationPhase IIOf noteour initial studies and the approach herein meet published FDA expectations for blood substitutesGiven the significant potential for Department of DefenseDoDcollaboration and supportwe have chosen to pursue hemorrhagic shock as the first indication for FDA approvalOur strategy to accelerate EM to human study involves collaborating with the DoD on a highly prioritized project to develop aMultifunctional Resuscitation FluidMRFWe have established firm collaborations with the US Army and the MRF programwhich currently lacks an OcarrierFollowing a successful trial for hemorrhagic shockwe would expand EM into other settingspre hospital useblood banking in the developing worldand exploit the design to extend efficacies beyond that of stored bloodPROJECT NARRATIVE There is need for an artificial oxygen carrier to care for anemic and bleeding patients in settings in settings where donated human blood is unavailable or undesirableTo address this needwe developedErythroMerEMa first in class nano cyte blood substitute and founded KaloCyte to we may translate these innovations into a pragmatic therapeuticThis proposal will support that effort