Positive Phase 1b/2a Interim Data for BB-301 in OPMD Patient Treatment

On April 18, 2024, Benitec Biopharma Inc., a clinical-stage biotechnology company specialized in gene therapy, announced positive interim clinical data for BB-301, following its administration to the first subject in a Phase 1b/2a clinical trial targeting Oculopharyngeal Muscular Dystrophy (OPMD). This study is designed as a single-arm, open-label, sequential, dose-escalation cohort investigation. BB-301 has received Orphan Drug designation from both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) Committee for Orphan Medicinal Products (COMP).

Jerel A. Banks, M.D., Ph.D., Executive Chairman and CEO of Benitec, highlighted the significance of these results, noting the absence of previous clinical studies showing systematic improvements in OPMD patients' swallowing ability. The interim data revealed improvements based on both radiographic measures and patient-reported outcomes from the initial subject treated with BB-301. These encouraging results offer hope to patients and caregivers, and the company intends to continue monitoring and treating patients entering the dosing phase from the natural history observational lead-in period.

BB-301 Interim Clinical Study Results:

During the OPMD Natural History Study, which serves as the pre-dosing observational period, the first subject demonstrated progressive worsening of dysphagia, as shown by videofluoroscopic swallowing studies (VFSS), the cold water timed drinking test, and the Sydney Swallow Questionnaire. VFSS is the gold standard for quantitatively assessing dysphagia in clinical settings.

At the 90-day timepoint after BB-301 administration, the first subject showed improvements in key VFSS assessments. These improvements correlated with enhancements in the Sydney Swallow Questionnaire results compared to pre-dosing averages. Notably, many assessments from the 90-day timepoint were improved compared to measurements taken more than 12 months prior.

The most notable VFSS improvements at Day 90 were observed in tasks evaluating pharyngeal constrictor muscle function and swallowing efficiency when consuming thin liquids, solid foods, and thick non-solid foods, such as yogurt or pudding. These VFSS advancements mirrored the improvements noted in the Sydney Swallow Questionnaire, indicating better swallowing functionality as reported by the subject.

Regarding BB-301's safety profile, no Serious Adverse Events have been reported for the two subjects who received the treatment. Both subjects experienced transient Grade 2 Gastroesophageal Reflux Disease (GERD), which resolved after a short course of standard prescription medications for GERD.

OPMD is a rare progressive muscle-wasting disorder caused by a mutation in the poly(A)-binding protein nuclear 1 (PABPN1) gene. It is characterized by swallowing difficulties (dysphagia), limb weakness, and eyelid drooping (ptosis). Over time, dysphagia can lead to severe complications such as chronic choking, regurgitation, aspiration pneumonia, and potentially death. Current clinical and surgical interventions are limited in scope and do not address the underlying muscle weakness.

BB-301 is an innovative therapy using a modified AAV9 capsid expressing a unique bifunctional construct to co-express codon-optimized Poly-A Binding Protein Nuclear-1 (PABPN1) and two small inhibitory RNAs (siRNAs) targeting mutant PABPN1. The siRNAs silence the expression of defective mutant PABPN1 while allowing the expression of functional codon-optimized PABPN1, effectively treating OPMD by halting the mutant gene's expression and providing a functional replacement protein.

Benitec Biopharma Inc. focuses on developing novel genetic medicines based on the proprietary "Silence and Replace" platform that combines RNA interference (RNAi) with gene therapy to create treatments that both silence disease-causing genes and deliver replacement genes in a single administration. The company is headquartered in Hayward, California, and is leading advancements in treatments for conditions like OPMD.