Benitec Biopharma Inc. (NASDAQ: BNTC) announced that its independent Data Safety Monitoring Board (DSMB) has recommended continuation of the Phase 1b/2a clinical trial for BB-301, a novel gene therapy for oculopharyngeal muscular dystrophy (OPMD), following completion of comprehensive safety review for all six subjects enrolled in Cohort 1.
The DSMB convened following the completion of the 28-day post BB-301 dosing visit for the sixth subject enrolled into Cohort 1, in accordance with the clinical trial protocol (NCT06185673). The sixth and final subject of Cohort 1 was safely treated with the low dose of BB-301 in April 2025.
Trial Progression and Safety Profile
Following the positive DSMB recommendation, enrollment of Cohort 2 is expected to begin in Q4 2025. "We are extremely thankful and humbled to have the opportunity to continue our collaborative development work for BB-301 with the OPMD patient community and the OPMD clinical community," said Jerel A. Banks, M.D., Ph.D., Executive Chairman and Chief Executive Officer of Benitec.
The company highlighted the benign safety profile of BB-301 associated with its local route of direct intramuscular delivery. This administration method enables the use of lower doses of the gene therapy agent relative to doses employed for other gene therapy programs that rely on systemic routes of administration.
Novel "Silence and Replace" Mechanism
BB-301 represents a novel approach to treating OPMD through Benitec's proprietary "Silence and Replace" DNA-directed RNA interference (ddRNAi) platform. The therapy is a modified AAV9 capsid expressing a unique, single bifunctional construct that promotes co-expression of both codon-optimized Poly-A Binding Protein Nuclear-1 (PABPN1) and two small inhibitory RNAs (siRNAs) against mutant PABPN1, the causative gene for OPMD.
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. The company believes this silence and replace mechanism uniquely positions BB-301 for OPMD treatment by halting mutant expression while providing a functional replacement protein.
Clinical Development Timeline
Additional clinical study updates for subjects enrolled in Cohort 1 are planned for the fourth calendar quarter of this year. The Phase 1b/2a clinical treatment study represents a critical step in advancing BB-301 toward potential commercialization for patients with OPMD.
Benitec's proprietary platform combines RNA interference with gene therapy to create medicines that simultaneously facilitate sustained silencing of disease-causing genes and concomitant delivery of wildtype replacement genes following a single administration of the therapeutic construct. The clinical-stage biotechnology company, headquartered in Hayward, California, is focused on developing Silence and Replace-based therapeutics for chronic and life-threatening human conditions.
