NeuBase Therapeutics, Inc. announced a broad set of preclinical safety and efficiency data for its Stealth Editors development program that demonstrate the ability to achieve gene editing with a non-immunogenic system. These preclinical data were featured in an oral presentation by Dr. Dani Stoltzfus, Vice President of Research at NeuBase, titled, "Nuclease-Free Gene Editing with Peptide Nucleic Acids: A New Class of In Vivo Gene Editors, at the ASGCT 2023 Annual Meeting. These data support novel in vivo gene editing approach that allows to tag a locus in the genome that harbors a mutation with a simple synthetic compound and recruit the cell's own machinery to repair the mutation.

This high-fidelity non-immunogenic approach is expected to offer advantages compared to modified bacterial CRISPR/Cas enzymes for in vivo gene editing applications from a safety and durability of effect perspective," stated Dietrich A. Stephan, Ph.D., Founder and Chief Executive Officer of NeuBase. Ex vivo editing with Stealth Editors - The Company investigated the capabilities of a new editing system to effectively edit human cells ex vivo. The editing system is comprised of two synthetic reagents: a modifiedpeptide nucleic acid and an oligonucleotide donor molecule.

Human cells were modified to contain a fluorometric reporter system that allows rapid and real-time colorimetric readout of correction of a frameeshift mutation in the genome. The result of the studies showed a dose-dependent increase in correction of the gene mutation based on expression of the newly functional fluorescent protein compared with various controls, highlighting a titratable increase in efficiency with which the Stealth Editors can engage the genome to harness the cell's own machinery to correct the mutation. The Company has made strides toward increasing editing efficiency over the past months and believes efficiency will continue to increase with technical improvements.

This ex vivo fluorometric system is rapidly modifiable to include any gene editing target of interest and allow rapid screening against diverse targets to identify hits, supporting both the Company's emerging in-house pipeline of therapeutic programs, which the Company plans to announce later this year, as well as potential research partnerships. Proven Non-Immunogenic profile 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 a lipid nanoparticle. The results of this study show PBMCs treated with a Stealth Editor did not impact cell viability.

In addition, there was no cellular immune response for the Stealth Editor-treated cells compared with the control (PBS) across the five cytokines measured, in direct juxtaposition to the positive controls, which elicited a strong cytokine response. The conclusion from these data is that Stealth Editors do not elicit innate immune responses in the encapsulated format in which they would be administered systemically, and the Company believes this is likely to be an important differentiator of its technology when transitioned to in vivo gene editing. Delivered via Non-Immunogenic Delivery Technology – Using clinically-validated technology, the Company has generated Stealth Editor lipid nanoparticles (LNP) where the hydrodynamic diameter is approximately 70 nm, and the polydispersity index is <0.1. Furthermore, the Company's drug product has a physiologically acceptable pH of 7.3 and an osmolality in the range of 300.

These data demonstrate that NeuBase has overcome the challenge of how to encapsulate Stealth Editors and sets the stage to move this program into in vivo studies.