NeuBase Therapeutics Presents New Preclinical Data for its Myotonic Dystrophy Type 1 Program Demonstrating Splice Rescue, Nuclear Aggregate Resolution & Myotonia Reversal

NeuBase Therapeutics, Inc. recently announced new preclinical data for its lead development candidate, NT-0231.F, to treat myotonic dystrophy type 1 (DM1).

Sandra Rojas-Caro, MD, Chief Medical Officer of NeuBase, said “DM1 is a significant unmet medical need characterized by myotonia, muscle weakness and wasting, and cognitive impairments. We are excited to present new preclinical data for our lead candidate, NT-0231.F, to support our differentiated approach for DM1. Systemic administration of NT-0231.F achieves clinically relevant molecular and functional rescue in the muscle in the HSA^LR model, which reproduces many components of the disease. Initial pharmacokinetic data supports a whole-body solution to the disease, and additional preclinical work is in progress to assess biodistribution in key tissues. These data are an important milestone in our DM1 development program and support our pursuit of a best-in-class therapeutic profile for the disease.”

A single intramuscular dose confirmed that NT-0231.F is pharmacologically active in the muscle and drives molecular and functional rescue in the HSA^LR model, including splice rescue, nuclear aggregate resolution, and myotonia (delayed muscle relaxation after contraction) reversal. A single intravenous (IV) dose of NT-0231.F or multiple subcutaneous (SC) doses over a 28-day period broadly rescued splicing, including the chloride channel (Clcn1) transcript, and reversed myotonia in the model. A single IV dose of NT-0231.F provides initial splice rescue at around two weeks, with significant splice rescue around three weeks. Myotonia reversal was achieved at around four weeks, with effects enduring to at least six weeks, the longest time point tested so far. A time course of multiple SC doses across increasing concentrations of NT-0231.F was also investigated and showed splice rescue and myotonia reversal in a dose-responsive manner, illustrating feasibility of the differentiated and patient-friendly SC route. In pharmacokinetic studies of NT-0231.F in wild-type BALB/C mice, a single IV or SC dose showed high volume of distribution, suggesting wide tissue distribution.

Dietrich A. Stephan, PhD, Founder, Chief Executive Officer, and Chairman of NeuBase, added “We now have preclinical data in the gold-standard animal model for our development candidate demonstrating robust reversal of myotonia, as measured by muscle relaxation in these studies. We believe we are the only company that has shown improved muscle relaxation after systemic routes of administration. The HSA^LR model is also a high bar for human disease in that it contains at least 10x more mutant gene CUG- repeat targets than patients, giving us further conviction in the robustness of our approach. Not only does this data support the further advancement of our lead program in DM1 and keep us on track for submitting an Investigational New Drug application to the U.S. Food and Drug Administration in 4Q CY2022, it also validates that we can utilize our PATrOL platform to design novel genetic medicines that target and rescue many other gene dysfunctions, with the potential for clinically impactful outcomes in both rare and common diseases.”

Patients with DM1 suffer from cognitive deficits and muscle pathology caused by a trinucleotide expansion in the DMPK gene which, when transcribed, results in an RNA hairpin structure that sequesters RNA splice proteins. NeuBase’s DM1 investigational genetic therapy, NT-0231.F, targets mutant DMPK pre-mRNA with a novel peptide-nucleic acid (PNA) pharmacophore and is designed to selectively engage with the toxic RNA hairpin structure, release the splicing proteins, and restore RNA splicing and downstream protein production. The PNA pharmacophore is conjugated to NeuBase’s novel delivery technology that is designed for broad distribution, including into the deep brain, with the potential for a whole body, disease-modifying solution for DM1.

NeuBase is accelerating the genetic revolution by developing a new class of precision genetic medicines that Drug the Genome. The company’s therapies are built on a proprietary platform called PATrOL that encompasses a novel peptide-nucleic acid antisense oligonucleotide technology combined with a novel delivery shuttle that overcome many of the hurdles to selective mutation engagement, repeat dosing, and systemic delivery of genetic medicines. With an initial focus on silencing disease-causing mutations in debilitating neurological, neuromuscular, and oncologic disorders, NeuBase is committed to redefining medicine for the millions of patients with both common and rare conditions, who currently have limited to no treatment options. For more information, visit www.neubasetherapeutics.com.