- 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
These preclinical data were featured in a poster presentation by Dr.
“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
“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
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 28th APS will be made available on the Publications and Presentations section of the NeuBase website (click here).
About
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
This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act. These forward-looking statements are distinguished by the use of words such as “will,” “would,” “anticipate,” “expect,” “believe,” “designed,” “plan,” “project,” or “intend,” the negative of these terms, and similar references to future periods. These forward-looking statements include, among others, those related to the potential and prospects of the Company’s proprietary PATrOL™ platform or Stealth Editing™ technology and the Company’s statements regarding potential collaborations. These views involve risks and uncertainties that are difficult to predict and, accordingly, our actual results may differ materially from the results discussed in our forward-looking statements. Our forward-looking statements contained herein speak only as of the date of this press release. Factors or events that we cannot predict, including those risk factors contained in our filings with the
NeuBase Investor Contact: Managing Director daniel@lifesciadvisors.com OP: (617) 430-7576 NeuBase Media Contact: media@neubasetherapeutics.com |
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