Q-State Biosciences Announces Pre-Clinical Proof-of-Concept Data for Exon-Skipping ASO Therapeutic in Ultra-Rare Neurological Disorder
CAMBRIDGE, Mass.–(BUSINESS WIRE)–Q-State Biosciences (“Q-State”), a discovery technology and therapeutics company advancing programs for the treatment of epilepsy, pain, and other disorders of the central nervous system, today announced new proof-of-concept data in non-human primates (NHP) for QSB-490, an exon-skipping antisense oligonucleotide (ASO) therapeutic candidate. QSB-490 is currently in development for the treatment of spastic paraplegia type 49 (SPG49) associated with pathogenic mutations in exon 8 of the TECPR2 gene. SPG49 is an ultra-rare neurological disorder characterized by intellectual disability, impaired speech, hypotonia, spasticity, severe motor delay, gastroesophageal reflux, areflexia, central sleep apnea and premature death. QSB-490 was developed in partnership with the Luke Heller TECPR2 Foundation.
Initial data from the preclinical single-dose study of QSB-490 showed measurable increases in the level of TECPR2 exon 8-skipping transcript above background in what may be the first reported instance of ASO-induced exon skipping in NHP brain tissue. A positive correlation between ASO concentration and degree of exon 8-skipping transcript was observed among a subset of brain regions that mediate respiratory control (pons and medulla) and cognition (frontal cortex) in both the left and right brain hemispheres. These results support previous preclinical findings which demonstrated that QSB-490 effectively rescued TECPR2 protein expression in dermal fibroblasts and induced pluripotent stem cell-derived neurons from a SPG49 patient, where TECPR2 also showed localization to neuronal compartments consistent with that visualized in healthy control neurons.
“Together, these data suggest that QSB-490 is a promising early therapeutic candidate for SPG49 patients with TECPR2 exon 8 mutations,” said Paul Medeiros, President and Chief Executive Officer of Q-State Biosciences. “This discovery highlights the powerful capabilities of our technology platform in discovering novel genetic medicines.”
Q-State expects to present full data from the study of QSB-490 in NHP at an appropriate scientific meeting later this year. In addition, the company anticipates initiation of a clinical trial in conjunction with the Luke Heller TECPR2 Foundation during the second half of this year.
About Q-State Biosciences
Q-State Biosciences is a discovery technology and therapeutics company based in Cambridge, Massachusetts. We integrate advanced human neuronal models, proprietary determinative measurement engineering and powerful AI/machine learning to discover and develop novel therapeutics for epilepsy, pain, and other disorders of the CNS. For more information, please visit www.qstatebio.com.