Decibel Therapeutics Receives FDA Clearance of IND Application for DB-OTO, a Gene Therapy Product Candidate Designed to Provide Hearing to Individuals…

The IND for DB-OTO provides clearance for the Company to initiate a pediatric Phase 1/2 clinical trial in the U.S. inchildren 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 Decibels 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 Decibels pipeline to advance into clinical testing. In June 2022, Decibel reported positive data from the interim analysis of the Companys 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.

About Decibel TherapeuticsDecibel 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. Decibels 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 about Decibel Therapeutics, please visit http://www.decibeltx.com or follow us on Twitter.

Forward-Looking Statements

This press release contains forward-looking statements that involve substantial risks and uncertainties. All statements, other than statements of historical facts, contained in this press release, including statements regarding Decibels strategy, future operations, prospects, plans, objectives of management, the therapeutic potential for Decibels product candidates and preclinical programs, the potential benefits of cell-selective expression, plans to submit one or more CTAs in Europe and the expected timeline for initiating a Phase 1/2 clinical trial of DB-OTO constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. The words anticipate, believe, continue, could, estimate, expect, intend, may, might, objective, ongoing, plan, predict, project, potential, should, or would, or the negative of these terms, or other comparable terminology are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Decibel may not actually achieve the plans, intentions or expectations disclosed in these forward-looking statements, and you should not place undue reliance on these forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in these forward-looking statements as a result of various important factors, including: uncertainties inherent in the identification and development of product candidates, including the timing of and Decibels ability to obtain approval to initiate clinical development of its program candidates, whether results from preclinical studies will be predictive of the results of later preclinical studies and clinical trials, whether Decibels cash resources are sufficient to fund its foreseeable and unforeseeable operating expenses and capital expenditure requirements, uncertainties related to the impact of the COVID-19 pandemic on Decibels business and operations, as well as the risks and uncertainties identified in Decibels filings with the Securities and Exchange Commission (SEC), including those risks detailed under the caption Risk Factors in Decibels Quarterly Report on Form 10-Q for the quarterly period ended June 30, 2022 and in other filings Decibel may make with the SEC. In addition, the forward-looking statements included in this press release represent Decibels views as of the date of this press release. Decibel anticipates that subsequent events and developments will cause its views to change. However, while Decibel may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing Decibels views as of any date subsequent to the date of this press release.

Investor Contact:Julie SeidelStern Investor Relations, Inc.julie.seidel@sternir.com212-362-1200

Media Contact:Chris RaileyTen Bridge CommunicationsChris@tenbridgecommunications.com617-834-0936

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Decibel Therapeutics Receives FDA Clearance of IND Application for DB-OTO, a Gene Therapy Product Candidate Designed to Provide Hearing to Individuals...