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

• New preclinical data validates that Stealth Editors™ are non-immunogenic, as featured in a poster presentation at the 28th American Peptide Symposium

• First non-human primate (NHP) study to successfully redose a gene editor without an immune response

• Ex vivo data show Stealth Editors™ are titratable, and editing efficiency is in range for clinical benefit in various conditions

• Company expects to present additional data showcasing gene editing capabilities of Stealth Editors™ throughout remainder of 2023
  

PITTSBURGH, June 29, 2023 (GLOBE NEWSWIRE) -- NeuBase Therapeutics, Inc. (Nasdaq: NBSE) (“NeuBase” or the “Company”), a biotechnology company developing Stealth Editors™ to perform in vivo gene editing without triggering the immune system, today announced a broad set of preclinical data, including non-human primate (“NHP”) repeat dosing 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 a poster presentation by Dr. Dani Stoltzfus, Vice President of Research at NeuBase, titled, “Stealth Editing™ With Peptide Nucleic Acids: A New Class of In Vivo Gene Editors,” at the 28^th American Peptide Symposium (APS), which is being held in Scottsdale, AZ, from June 24-29, 2023.

“We are pleased to report that no innate nor acquired immune responses in NHPs were observed after repeat dosing of our Stealth Editor, as measured across a panel of key cytokines after each dose. We believe this is the first NHP study that has successfully redosed a gene editor without observing an immune response for either dose,” stated Dietrich Stephan, Ph.D., Founder and Chief Executive Officer of NeuBase.

“Patient immune reactions against gene therapies are well documented and can result in serious adverse events, including death, along with a lack of pharmacology due to neutralizing antibodies. We are beginning to see reports of immune responses after delivery of gene editing solutions, possibly due to viral vector-based delivery or the expression of bacterial nucleases in vivo. For these reasons, we are on a mission to develop the next generation of editors that are non-immunogenic,” continued Dr. Stephan. “Our nuclease-free synthetic editors resemble oligonucleotides, but can uniquely engage the double-stranded human genome and harness the cell’s own DNA repair machinery to elicit editing. We believe this lack of immunogenicity also enables repeat dosing, should tissue editing efficiency thresholds be high or if durability wanes with time. These latest data support a differentiated pipeline of in vivo editing therapeutic programs, which we expect to announce later this year, as well as the pursuit of additional partnerships with pharmaceutical and agricultural partners in areas of mutual interest,” concluded Dr. Stephan.

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.
  
  The result of the study showed a dose-dependent increase in the 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 poster for the Stealth Editors data updates at the 28^th APS will be made available on the Publications and Presentations section of the NeuBase website (click here).

About NeuBase Therapeutics

NeuBase is a preclinical stage biopharmaceutical company leveraging its peptide nucleic acid technology to accelerate the genome editing revolution. NeuBase's Stealth Editing™ technology is a new type of gene editing designed to avoid being identified by the immune system and provide pronounced effects that are safe, delivered with non-viral technologies, and broadly applicable across different mutation types and industries. This in vivo gene editing system seeks to address disease at the base level by recruiting the body’s own editing machinery to correct mutations that cause disease. The Company projects that its technology can potentially address up to ~90% of all known human mutations, including insertions, deletions, transitions, and transversions with a simple non-immunogenic solution. To learn more, visit www.neubasetherapeutics.com.

Use of Forward-Looking Statements

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Released June 29, 2023