Decibel Therapeutics Inc (DBTX)

[makinezmoney]

$DBTX: Something is up........ now at 2.30


Watching closely here

https://www.decibeltx.com/

https://ir.decibeltx.com/node/7566/pdf





GO $DBTX



********************************************************************************


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.