NeuBase Presents Non-Human Primate Data Illustrating Stealth Editors are Non-Immunogenic, Opening the Door to Redosing - Seite 2

Overview of Preclinical Studies and Results Presented at APS 2023:

• Stealth Editors are Non-Immunogenic in Non-Human Primates (NHPs) - The Company demonstrated that Stealth Editors do not elicit an innate nor acquired immune response in NHPs as measured by a cytokine panel:
  • Cynomolgus NHPs (four groups of n=3 per group) were given two doses of an intravenous administration, on days 1 and 29: (1) vehicle control; (2) MC3 lipid nanoparticle (LNP) control; (3) 0.10 mg/kg Stealth Editor encapsulated in an LNP; and (4) 0.16 mg/kg Stealth Editor co-encapsulated with a single-stranded oligonucleotide donor in an LNP;
  • On days 0, 1 and 29, blood was drawn and serum was assessed for IFN-gamma, IL-2, IL-6, IL-8, IL10 and IL-1β cytokine induction using a Meso Scale Discovery (MSD) multi-spot assay;
  • Normal cytokine ranges were identified in healthy untreated cynomolgus monkeys (n=30) by MSD; and
  • All absolute values of cytokines were within the historical control ranges.

The conclusion from these data is that Stealth Editors do not elicit innate nor acquired immune responses in the encapsulated format in which they would be administered systemically. The Company believes this is likely to be an important differentiator of its technology when transitioned to in vivo gene editing.

• Stealth Editors are Non-Immunogenic in Human Peripheral Blood Mononuclear Cells (PBMCs) - The Company demonstrated the stealth nature of its editing solution with PBMCs from multiple donors treated with either known immunostimulants or Stealth Editors packaged inside LNPs. The results of this study show PBMCs treated with a Stealth Editor did not impact cell viability, nor did the editors elicit an immune response.

• Ex vivo Editing with Stealth Editors - The Company investigated the capabilities of a new editing system to effectively edit human cells ex vivo. The data from this study show the new system – comprised of two synthetic reagents: a modified peptide nucleic acid (PNA) and an oligonucleotide donor molecule – is titratable, and editing efficiency is in range for clinical benefit in various conditions and continues to increase with optimization. In the study, human cells were modified to contain a fluorometric reporter system that allows rapid and real-time colorimetric readout of correction of a frameshift mutation in the genome.