Benitec Biopharma announced on October 28, 2026, interim results from its ongoing phase 1b/2a first-in-human study of BB-301, an investigational gene therapy for dysphagia in patients with oculopharyngeal muscular dystrophy (OPMD).¹ All 9 patients treated to date, 6 at a low dose and 3 at a high dose, were classified as formal responders to therapy. The high-dose cohort showed greater relative improvements at 3 months in throat emptying ability and functional swallowing capacity.¹ The data were accepted as a late-breaking abstract at the Annual Congress of the European Society of Gene and Cell Therapy (ESGCT).¹
Key facts
- Drug: BB-301 (Benitec Biopharma)
- Class: AAV9-based ddRNAi Silence and Replace gene therapy
- Indication studied: OPMD-related dysphagia
- Trial: NCT06185673; phase 1b/2a, open-label dose escalation
- Response: 9 of 9 patients are formal responders
- Dose signal: greater 3-month gains in throat emptying and swallowing capacity with high dose
- Safety: no serious adverse events to date
- Regulatory status: pivotal design confirmation expected first quarter 2027 (FDA)
- Designations: orphan drug and fast track (FDA); orphan drug (EMA)
"Progressive loss of swallowing function has a devastating impact on OPMD Patients, yet there are no approved therapies to address this critical unmet medical need," said Jerel A. Banks, MD, PhD, executive chairman and CEO of Benitec, in a company press release.¹
What did the interim analysis show?
The open-label, dose-escalation study (NCT06185673) is evaluating the safety and clinical activity of intramuscular BB-301 in patients with OPMD and dysphagia.¹,² The update included 12-month follow-up for all 6 patients in cohort 1 (low dose), 9-month follow-up for the first patient in cohort 2 (high dose), and 3-month follow-up for the remaining 2 cohort 2 patients.¹
Benitec compared the full cohorts at 3 months, when complete results were available for both. Improved throat emptying ability was assessed by videofluoroscopic evaluation of post-swallow food and liquid residue. It met the statistical criteria for response in 67% of cohort 1 patients and 100% of cohort 2 patients.¹ Improved functional swallowing capacity, assessed by the Cold-Water Timed Drinking Test, met response criteria in 17% and 67% of patients, respectively.¹
Other measures were equivalent between doses at 3 months. All patients in both cohorts met response criteria for improved total Sydney Swallow Questionnaire score, and 67% in each cohort met response criteria for improved throat closing ability.¹ No serious adverse events have been reported in any patient treated with BB-301 to date.¹
How does BB-301 work?
BB-301 uses a modified adeno-associated virus serotype 9 (AAV9) capsid to deliver a single bifunctional construct based on Benitec's Silence and Replace DNA-directed RNA interference platform.¹ The construct expresses 2 small inhibitory RNAs that silence the mutant poly(A)-binding protein nuclear 1 (PABPN1) gene that causes OPMD. It also expresses a codon-optimized functional version of PABPN1.¹ The therapy is given once, locally, into the throat muscles that drive swallowing, an approach designed to limit systemic exposure.¹
