Document text
Principal Investigator: Esma Alp
Organization: KALOCYTE, INC.
Fiscal Year: 2023
Award: $1,050,000
Funding agency: National Heart Lung and Blood Institute
Research Summary/Abstract
ErythroMer (EM) is a novel biosynthetic blood substitute developed to address the critically unmet need for
emergency transfusion in situations where the use of banked red blood cells (RBCs) are either not available or
undesirable. EM is a self-assembled lipid-oligomeric hybrid nanoparticle with a high per particle payload of
hemoglobin (Hb) and the allosteric modifier, RSR13. EM is specifically designed to rectify failures of previous
hemoglobin-based oxygen carriers, which do not preserve RBC physiology. The bio-inspired EM design
surmounts previous obstacles by emulating RBC features: long term stability, precise dynamically-responsive
allosteric effector control of Hb oxygen affinity, control of Hb interaction with nitric oxide (NO), preventing
vasospasm, and mitigation of hemoglobin oxidation by containment in the vascular compartment. EM is designed
for sterile lyophilization enabling extended shelf life at ambient conditions and offers cost-effective production at
scale. KaloCyte has developed a pragmatic yet robust step-wise goal oriented development plan for
commercialization including meticulous evaluation of preclinical safety to support FIH dosing. A systematic and
rigorous in vitro, ex vivo and animal model based pre-clinical proof-of-concept strategy provides strong evidence
supporting the premise for and feasibility of this proposal. Further, our commitment to characterize a
comprehensive non-GLP pharmacokinetic and exploratory toxicology as well as an FDA vetted GLP toxicology
plan for EM is elucidated. To meet these milestones in a timely fashion, non-GLP dose dependent
pharmacokinetic studies of EM that probe tissue distribution, metabolism, and elimination and exploratory
toxicology studies will be conducted. Successful completion of these experimental studies will inform on
pharmacokinetic behavior, potential dose dependent safety signals and product quantity needs, moving forward
into GLP toxicology studies and eventually FIH dosing. The described, comprehensive dose dependent
toxicology studies are tailored to meet FDA expectations that allows for dosing of EM in a Phase 1 clinical trial.
This process requires, escalating single dose toxicology study in rabbits expanded to 14 days for post dose
recovery. Parallel studies investigating cardiac electrophysiology, pulmonary hemodynamics, and systemic
hemodynamics in a dog safety pharmacology study with an added toxicokinetic arm. Completion of these IND-
enabling studies provides necessary pre-clinical animal data qualifying KaloCyte to submit an IND package for
EM. EM has the capability to dramatically transform care in situations where the adverse effects of stored RBCs
exceed benefit and may enable novel efficacies. However, the most compelling use will be in settings where
stored RBCs are unavailable or undesirable.
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Terms: <Acute><Address><Adverse effects><Affinity><Animal Model><Animal Models and Related Studies><Animals><Antioxidants><Artificial Blood><Artificial Erythrocytes><Authorization><Authorization documentation><Behavior><Biodistribution><Biological><Biomedical Engineering><Biotech><Biotechnology><Bleeding><Blood><Blood Plasma><Blood Reticuloendothelial System><Blood Substitutes><Blood Vessels><Blood erythrocyte><Blood leukocyte><Body Tissues><Body Weight><Canine Species><Canis familiaris><Cardiac Electrophysiologic Techniques><Cardiac Electrophysiological Diagnostics><Caring><Cell Communication and Signaling><Cell Function><Cell Process><Cell Signaling><Cell physiology><Cellular Function><Cellular Physiology><Cellular Process><Clinical><Clinical Chemistry><Clinical Trials><Clotting><Coagulation><Coagulation Process><Complement Activation><Complex><Containment><Control Animal><Core Particle><Cytokine Activation><Development><Development Plans><Diffusion><Dogs><Dogs Mammals><Domestic Rabbit><Dose><Drug Kinetics><Drug or chemical Tissue Distribution><Early-Stage Clinical Trials><Elements><Emergencies><Emergency Situation><Endogenous Nitrate Vasodilator><Endothelium-Derived Nitric Oxide><Ensure><Erythrocyte Substitutes><Erythrocytes><Erythrocytic><Evaluation><Evolution><Excretory function><Failure><Feedback><Fluorocarbons><Freeze Drying><Freeze Dryings><Gases><Goals><Hematology><Hemoglobin><Hemolysis><Hemorrhage><Human><Hybrids><In Vitro><Individual><Innate Immunity><Intermediary Metabolism><Intracellular Communication and Signaling><Kidney><Kidney Urinary System><Leukocytes><Leukocytes Reticuloendothelial System><Life><Lipids><Lung><Lung Respiratory System><Lyophilization><Marketing><Marrow erythrocyte><Marrow leukocyte><Medical Device><Metabolic><Metabolic Processes><Metabolism><Microscopic><Modern Man><Mononitrogen Monoxide><Morphology><Multiple Injuries><Multiple Trauma><Native Immunity><Natural Immunity><New Zealand><Nitric Oxide><Nitrogen Monoxide><Nitrogen Protoxide><Non-Specific Immunity><Nonspecific Immunity><Nucleosome Core><Nucleosome Core Particle><O element><O2 element><Organ Weight><Oryctolagus cuniculus><Oxygen><Particle Size><Pathology><Pathway interactions><Patient Care><Patient Care Delivery><Perfluorocarbons><Permission><Pharmaceutical Agent><Pharmaceuticals><Pharmaceutics><Pharmacokinetics><Pharmacologic Substance><Pharmacological Study><Pharmacological Substance><Pharmacology><Pharmacology Study><Pharmacy (field)><Phase><Phase 1 Clinical Trials><Phase I Clinical Trials><Physiologic><Physiological><Plasma><Plasma Serum><Platelet Activation><Process><Production><Productivity><Progenitor Cells><Qualifying><RSR-13><RSR13><RSR13 cpd><Rabbits><Rabbits Mammals><Recommendation><Recovery><Red Blood Cells><Red Cell><Red Cell Substitutes><Research><Reticuloendothelial System, Serum, Plasma><Risk><Rodent><Rodentia><Rodents Mammals><Safety><Shapes><Signal Transduction><Signal Transduction Systems><Signaling><Site><Sterility><Subcellular Process><Surface><Testing><Tissue Distribution><Tissues><Toxic effect><Toxicities><Toxicokinetics><Toxicology><Transfusion><Update><Vasospasm><White Blood Cells><White Cell><animal data><anti-oxidant><arm><authority><bio-engineered><bio-engineers><biocompatibility><bioengineering><biologic><biological engineering><biological signal transduction><biomaterial compatibility><blood corpuscles><blood loss><canine><cardiac electrophysiology><commercialization><complement pathway regulation><cost effective><design><designing><developmental><diffused><diffuses><diffusing><diffusions><domestic dog><endothelial cell derived relaxing factor><erythrolysis><excretion><expectation><experiment><experimental research><experimental study><experiments><first in man><first-in-human><food consumption><good laboratory practice><hemocompatibility><hemodynamics><innovate><innovation><innovative><longitudinal imaging><model of animal><nano><nano materials><nano meter scale><nano meter sized><nano particle><nano scale><nano-sized particle><nanomaterials><nanometer scale><nanometer sized><nanoparticle><nanoscale><nanosized particle><new drug treatments><new drugs><new pharmacological therapeutic><new therapeutics><new therapy><next generation therapeutics><novel><novel drug treatments><novel drugs><novel pharmaco-therapeutic><novel pharmacological therapeutic><novel therapeutics><novel therapy><oxidation><particle><pathway><pharmaceutic><pharmaceutical><phase I protocol><point of care><polytrauma><portability><pre-clinical><pre-clinical evaluation><pre-clinical safety><pre-clinical study><preclinical><preclinical evaluation><preclinical safety><preclinical study><prevent><preventing><pulmonary><reconstitute><reconstitution><renal><safety practice><safety study><self assembly><serial imaging><stem cells><sterile><trial design><vascular><white blood cell><white blood corpuscle>