Benitec Biopharma Inc. announced the U.S. Food and Drug Administration has cleared its Investigational New Drug application for BB-301, its silence and replace gene therapy for the treatment of Oculopharyngeal Muscular Dystrophy-related Dysphagia. Oculopharyngeal Muscular Dystrophy is a chronic, life-threatening genetic disorder affecting approximately 15,000 patients in the United States, Canada, Western Europe, and Israel. OPMD patients lose the ability to swallow liquids and solids, resulting in chronic malnutrition, aspiration, and fatal episodes of aspiration pneumonia.

Currently, there are no approved therapeutic agents for the treatment of OPMD. Subjects from Benitec’s ongoing NH study will be eligible for rollover onto the Phase 1b/2a clinical study of BB-301 for the treatment of OPMD-related Dysphagia after 6 months of baseline data collection. Following a 1-day dosing procedure for BB-301, each study subject will be evaluated for the same radiographic and clinical outcome measures as were evaluated during the NH study, including quantitative radiographic swallowing studies to facilitate objective assessments of swallowing safety, swallowing efficiency, and functional performance of the pharyngeal muscles underlying the OPMD-related Dysphagia.

Currently, there are 13 subjects enrolled into the NH study, with each subject having the potential to rollover onto the Phase 1b/2a clinical dosing study for BB-301. Interim safety and efficacy data is expected to become available from the BB-301 Phase 1b/2a study approximately every 90 days following the dosing of each subject. BB-301 is a novel, modified AAV9 capsid expressing a unique, single bifunctional construct promoting co-expression of both codon-optimized Poly-A Binding Protein Nuclear-1 (PABPN1) and two small inhibitory RNAs (siRNAs) against mutant PABPN1.

The two siRNAs are modeled into microRNA backbones to silence expression of faulty mutant PABPN1, while allowing expression of the codon-optimized PABPN1 to replace the mutant with a functional version of the protein. believe BB-301’s silence and replace strategy is uniquely positioned for the treatment of OPMD by halting mutant expression while providing a functional replacement protein.