Decibel Therapeutics Receives FDA Clearance of IND Application for DB-OTO, a Gene Therapy Product Candidate Designed to Provide Hearing to Individuals with Otoferlin-Related Hearing Loss October 17, 2022 The IND for DB-OTO provides clearance for the Company to initiate a pediatric Phase 1/2 clinical trial in the U.S. in children and infants, and is part of an international regulatory strategy for clinical development One-time administration of DB-OTO has resulted in production of otoferlin protein and durable auditory brainstem responses to sound in a congenitally deaf rodent disease model DB-OTO is Decibel’s second hearing therapeutic candidate to enter clinical investigation BOSTON, Oct. 17, 2022 (GLOBE NEWSWIRE) -- Decibel Therapeutics (Nasdaq: DBTX), a clinical-stage biotechnology company dedicated to discovering and developing transformative treatments to restore and improve hearing and balance, today announced that it has received clearance from the U.S. Food and Drug Administration (FDA) for its Investigational New Drug (IND) application to initiate a Phase 1/2 clinical trial in pediatric patients of DB-OTO, its lead gene therapy product candidate. DB-OTO is designed to provide durable hearing in individuals born with profound congenital hearing loss due to an otoferlin deficiency. “We are thrilled to work with families, advocacy groups and clinicians in the deaf and hard of hearing community to advance DB-OTO into the clinic,” said Laurence Reid, Ph.D., Chief Executive Officer at Decibel. “Decibel has assembled a compelling preclinical data package showing that DB-OTO demonstrated a favorable tolerability profile and an ability to stably generate full-length otoferlin transcript, express otoferlin protein and provide hearing in animal models. We are at an exciting time in the development of a new wave of precision gene therapies for children who are deaf and hard of hearing.” DB-OTO is being developed in collaboration with Regeneron Pharmaceuticals and is an adeno-associated virus (AAV)-based, dual-vector, gene therapy product candidate. Otoferlin is a protein expressed in cochlear inner hair cells that enables communication between the sensory hair cells of the inner ear and the auditory nerve. Newborns born with mutations in the otoferlin gene have fully developed structures within the inner ear. However, these newborns have profound hearing loss because signaling between the ear and the brain is disrupted. DB-OTO uses a proprietary, cell-selective promoter to express the otoferlin transgene in hair cells, with the goal of enabling the ear to transmit sound to the brain and provide hearing. DB-OTO received Orphan Drug and Rare Pediatric Disease designations from the FDA in 2021. Currently, there are no approved pharmacologic treatment options for individuals with otoferlin-related hearing loss. In preclinical studies, Decibel observed that delivery of DB-OTO to the inner ear resulted in production of otoferlin protein and durable auditory brainstem responses to sound in a congenitally deaf, rodent otoferlin disease model. Preclinical studies in non-human primates demonstrated that the local delivery procedure for DB-OTO, an intra-cochlear injection using the surgical approach employed by neurotologists and pediatric otolaryngologists during a standard cochlear implantation procedure, resulted in successful distribution and expression of otoferlin protein across the cochlear length. The Phase 1/2 dose escalation clinical trial is designed to evaluate the safety, tolerability and efficacy of DB-OTO in pediatric patients with congenital hearing loss due to an otoferlin deficiency. In addition to safety and tolerability endpoints, established, clinically relevant, objective and behavioral measurements of hearing will be used as efficacy endpoints in the clinical trial. The auditory brainstem response, which was used to characterize dose-response of DB-OTO after intra-cochlear delivery in translational studies, will serve as an early, objective, clinically accepted readout of hearing thresholds in the clinical trial. “Otolaryngologists, audiologists and auditory scientists have long awaited the clinical realization of the promise of biological therapies for hearing loss. Gene therapy for congenital deafness represents one such intervention and it would be an understatement to say that clinicians in the field of hearing loss are quite excited to see its advancement into clinical trials,” said Jay Rubinstein, M.D., Ph.D., Professor and Virginia Merrill Bloedel Chair in Otolaryngology, Head and Neck Surgery at the University of Washington School of Medicine. Based on discussions with the FDA during the IND review period, Decibel expects the first two participants in the U.S. portion of the Phase 1/2 trial will be as young as seven years of age and that subsequent participants will include children as young as two years of age and infants younger than two years of age. The Company intends to provide an update on the design of the clinical trial in the future. The DB-OTO IND is part of an international regulatory strategy for development of DB-OTO, which also includes plans to submit one or more Clinical Trial Applications (CTAs) in Europe. DB-OTO is the second product candidate in Decibel’s pipeline to advance into clinical testing. In June 2022, Decibel reported positive data from the interim analysis of the Company’s Phase 1b clinical trial of DB-020, a novel, proprietary formulation of sodium thiosulfate (STS) designed to protect against hearing loss in cancer patients receiving cisplatin chemotherapy. In the data from the interim analysis, 88% of patients experienced ototoxicity in their placebo-treated ear, and of these patients, 87% were partially or completely protected from ototoxicity in their DB-020-treated ears.
Decibel Therapeutics Shares Continue to Rally After Good Study Data >DBTX 12:58 pm ET June 29, 2022 (Dow Jones) Print
By Colin Kellaher
Shares of Decibel Therapeutics Inc. surged more than 30% on Wednesday, extending Tuesday's gains after the clinical-stage biotechnology company reported positive study results.
The Boston company on Tuesday said interim data from a Phase 1b study of DB-020 support continued development of the drug in the protection against ototoxicity, or hearing loss, in cancer patients receiving cisplatin chemotherapy.
Decibel said 87% of patients who experienced ototoxicity in their placebo-treated ear were protected from the side effect in their ear treated with DB-020.
In a research note, Citi analyst Neena Bitritto-Garg, who has a "buy" rating and a $15 target price on Decibel shares, said the study data mark "a clear win" the company.
The analyst also noted that Decibel remains focused on its earlier-stage gene-therapy portfolio, with an ultimate goal of licensing DB-020 to a company with an oncology sales force.
Decibel shares, which rose 18.3% on Tuesday, were recently changing hands at $3.52, up 32.9%.
Decibel Therapeutics, Inc. is a clinical-stage biotechnology company. The Company is focused on discovering and developing transformative treatments for hearing and balance disorder. It is focused on restoring and improving hearing and balance through the restoration and regeneration of functional hair cells and non-sensory support cells within the inner ear. The Company has built a platform that integrates single-cell genomics and bioinformatics analyses, precision gene therapy technologies and its proficiency in inner ear biology. The Company’s pipeline product includes its gene therapy program, namely DB-OTO to provide hearing to individuals born with profound hearing loss due to mutation of the otoferlin (OTOF) deficiency. In addition to its gene therapy product candidate and programs, it is also developing a clinical-stage product candidate, DB-020, for the prevention of cisplatin-induced hearing loss. Its products pipeline also includes AAV.103, AAV.104, DB-ATO and AAV.201.