Decibel Therapeutics Reports on Continued Progress of Lead Gene Therapy Product Candidate & Presents Promising Preclinical Data Supporting Importance of Cell-Selective Transgene Expression Across Gene Therapy Pipeline

Decibel Therapeutics recently announced the presentation of preclinical data on its lead gene therapy product candidate, DB-OTO, as well as preclinical data highlighting the identification of proprietary, cell-selective promoters for three of its gene therapy pipeline programs at this year’s virtual 45^th Annual MidWinter Meeting of the Association for Research in Otolaryngology (ARO).

Decibel presented preclinical data supporting the company’s lead gene therapy product candidate, DB-OTO, a dual-vector adeno-associated investigational product candidate designed to restore hearing to individuals with profound, congenital hearing loss caused by mutations of the otoferlin gene. DB-OTO uses a proprietary, cell-selective promoter to control otoferlin transgene expression in hair cells, with the goal of enabling the ear to transmit sound to the brain and provide hearing. In previous preclinical studies, administration of DB-OTO resulted in restoration of functional otoferlin protein in mice and dose scaling and distribution in non-human primates (NHPs). New data presented at ARO further characterized expression of otoferlin over time following DB-OTO administration in mice and NHPs, demonstrating that otoferlin expression increased over the first several weeks before plateauing, consistent with the expression previously reported in mice that achieved stable functional recovery. Decibel also shared functional recovery and tolerability data associated with DB-OTO dosing over a 10-fold dose range in mice.

Decibel also presented new data at ARO on its preclinical AAV.103 program to treat GJB2-related hearing loss through selective expression of GJB2 in cells that normally express GJB2 and on its preclinical AAV.104 program to treat stereocilin-related hearing loss through selective expression of stereocilin in outer hair cells. These data demonstrated how the Company deploys its platform to develop novel, proprietary, cell-selective promoters and the potential advantages that cell-selective expression may confer to its gene therapy pipeline programs. Decibel is developing DB-OTO, AAV.103 and AAV.104 in collaboration with Regeneron Pharmaceuticals, and Decibel retains global commercial rights in the three programs.

“The work we presented at ARO this week highlights our approach for developing precision gene therapy candidates and the potential importance of selective transgene expression for the inner ear. Our programs targeting otoferlin, GJB2 and stereocilin each utilize this approach,” said John Lee, Chief Development Officer at Decibel. “The preclinical data we shared demonstrating identification of a promoter/enhancer combination that can mediate hearing recovery in a GJB2-deficient mouse model represents exciting progress towards the development of a gene therapy to restore hearing to individuals with GJB2-related hearing loss.”

Decibel Therapeutics is a clinical-stage biotechnology company dedicated to discovering and developing transformative treatments to restore and improve hearing and balance, one of the largest areas of unmet need in medicine. Decibel has built a proprietary platform that integrates single-cell genomics and bioinformatic analyses, precision gene therapy technologies and expertise in inner ear biology. Decibel is leveraging its platform to advance gene therapies designed to selectively replace genes for the treatment of congenital, monogenic hearing loss and to regenerate inner ear hair cells for the treatment of acquired hearing and balance disorders. Decibel’s pipeline, including its lead gene therapy product candidate, DB-OTO, to treat congenital, monogenic hearing loss, is designed to deliver on our vision of creating a world of connection for people with hearing and balance disorders. For more information, visit www.decibeltx.com.