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Principal Investigator: David R Tabatadze
Organization: ZATA PHARMACEUTICALS, INC.
Fiscal Year: 2021
Award: $717,598
Funding agency: National Heart Lung and Blood Institute
ABSTRACT
Presently, convalescent plasma (CP) transfusion is being developed as a therapy for COVID-19 patients
and as a prophylactic for high risk individuals. In addition, treatment with plasma or neutralizing antibody
preparations from convalescent patients could be the only treatment for emerging infectious diseases, for
which no other treatments may be available. At the same time, CP transfusion exposes the recipient to the risk
of transfusion transmitted diseases (TTD), a risk which is additionally exacerbated by the compromised
immune conditions of the critically ill patients. The limited number of current TTD blood tests does not provide
for full protection, restrict the critically limited donor’s pool and may not be available in some areas. Pathogen
Inactivation can provide the solution. Unfortunately, the currently utilized treatments for pathogen reduction in
plasma (solvent-detergent, pasteurization of dry heat, UV or gamma irradiations) are non-selective and can
compromise the quality of plasma’s neutralizing antibodies or other protective protein factors. We at ZATA
Pharmaceuticals have developed a new class of pathogen inactivators (ZPI) based on the natural polyamines
scaffold, which are truly selective in inactivating pathogens genomic molecules while sparing plasma proteins.
Our preliminary results show that ZPI have high reactivity toward nucleic acids and do not modify model
proteins (Cyt-C, RSV fusion protein) and animal sera growth factors. Using them, we inactivated different types
of pathogens (G+ and G- bacteria, mycoplasma, fungi, protozoa) and high titer preparations of enveloped or
non-enveloped viruses. Currently we are developing ZPI for pathogens reduction in transfusion red blood cells,
research funded by NIH SBIR grant (R44 HL145783). In this application we propose to adapt the new
pathogen inactivation process for treatment of convalescent plasma (CP) by: (1) using 6 virus species in
human plasma to select the optimal ZPI and conditions for pathogen inactivation in human plasma; (2) using
already developed analytical methods to establish conditions for complete neutralization and/or removal of the
residual inactivator from the treated plasma; (3) using specific antibodies against 4 virus species to
demonstrate by ELISA that the virus inactivation treatment has no effect on the binding of the antibodies to
their targets; (4) using neutralizing antibodies against SARS-CoV-2 S protein to demonstrate preservation of
the virus neutralizing properties of the antibodies after plasma treatment; (5) using repeated autologous
infusion of treated plasma to establish its in vivo the safety in the rabbit models.
After accomplishment of those initial goals we will apply for funding, including SBIR funding to complete, in
collaboration with New York Blood Center, its pre-clinical evaluation and to initiate phase I human trials, or
alternatively, will license the treatment procedure for completion of its development and marketing. Ultimately,
this proposal will lead to a safe and high quality convalescent human plasma for treatment or prophylactics of
COVID19 or other deadly diseases for which no other effective treatment is currently available.
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