Project 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 inaccessible or
undesirable. EM is a self-assembled lipid-peptidic hybrid nanoparticle with a high per particle payload of
hemoglobin (Hb) that is specifically designed to rectify failures of previous hemoglobin-based oxygen carriers,
which do not preserve key features of 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 via payload antioxidants. 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 stepwise goal-oriented development plan for GMP commercialization including the scale-
up and cGMP manufacturing of ErythroMer and its key ingredients, customized lipid precursor, and hemoglobin.
Previously completed studies on the synthesis and scale-up of the lipid precursor, and the purification of
hemoglobin from red blood cells (RBCs) have been extremely promising. These studies provide strong evidence
of the premise for and feasibility of this proposal and our commitment for the manufacturing scale-up, purification
and analytical method development, validation, and qualification of the lipid precursor. The pre-IND stage
preclinical studies require EM volumes larger than and at a quality that necessitates CDMO services. Successful
completion of the scale-up and analytical work proposed in the current submission will provide KaloCyte the
confidence in the manufacturing processes for KC1003, and that the components being used for the fabrication
of EM are of the highest quality and fall within the acceptable specifications required by the regulatory agencies.
The manufacturing scale-up of KC1003 will include scale specific optimization of key parameters for it
manufacturing such as temperature, time, pressure, and reactant concentrations at each step of its
manufacturing process. Analytical methods development, validation, and optimization for KC1003, shall be
performed as per ICH guidelines recommended by the FDA. Statistical analysis of methods validation data shall
be performed to demonstrate the validity of each method. Completion of these steps in the path to product
commercialization, will help complete IND-enabling preclinical studies for EM under strict GLP guidelines. EM
has the capability to dramatically transform care in life-threatening blood loss situations where stored red blood
cells (RBCs) are unavailable (ambulances, military and austere environments, undeveloped countries),
undesirable (situations in which risk of transfusion exceeds benefit), or in short supply (mass casualty events).
