ErythroMer: Nanoscale BioSynthetic Red Cell Substitute

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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Grant Number: 5R44HL135965-06
NIH Institute/Center: NIH
Principal Investigator: Esma Alp