NeuBase Therapeutics, Inc. announced new preclinical data for its lead development candidate, NT-0231.F, to treat myotonic dystrophy type 1 (DM1). These data are being presented in poster and oral presentations at the 2022 MDA Clinical & Scientific Conference, which is taking place virtually and in-person in Nashville, Tennessee from March 13-16, 2022. A single intramuscular dose confirmed that NT-0231.F is pharmacologically active in the muscle and drives molecular and functional rescue in the HSALR 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. 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.