A Study of DB-OTO, an Adeno-associated Virus (AAV) Based Gene Therapy, in Children/Infants With Hearing Loss Due to Otoferlin Mutations

Inclusion Criteria:

1. Presence of pathogenic or likely pathogenic mutations in both alleles of the OTOFgene.

2. Patient is <18 years of age and of the appropriate age to qualify for enrollment inthe corresponding age cohort at the time the parent/legal guardian signs theinformed consent form. Participant to provide assent, when applicable

3. Audiological Criteria: US:

• Investigator determines that minimal benefit has been provided by amplificationof the ear to receive DB-OTO.

• Investigator determines the patient meets cochlear implantation criteria inboth ears according to the recommended cochlear implant label Infants ≤24 months of age:

1. Profound sensorineural hearing loss (SNHL; ≥ 90 dB HL) based on behavioral andphysiologic measurements (ABR) of inner ear function.

2. Outer hair cell function is confirmed by presence of otoacoustic emissions (OAE) in the ear(s) to receive DB-OTO Children >24 months to <18 years of age:

3. Profound SNHL (≥ 90 dB HL) based on physiologic measurements (ABR) of inner earfunction AND

4. Behavioral open-set word recognition scores of < 30% in the ear that wouldreceive DB-OTO

5. Outer hair cell function is confirmed by presence of otoacoustic emissions (OAE) in the ear(s) to receive DB-OTO OR

6. Presence of a cochlear microphonic in ears to receive DB-OTO. UK & Spain: Infants ≤24 months of age:

7. Absence of an ABR neural signal in response to a click stimulus ≤85 dB nHL inthe ear(s) to be injected with DB-OTO.

8. Presence of otoacoustic emissions (OAE) in the ear(s) to receive DB-OTO. Children >24 months to <18 years of age:

9. Absence of an ABR neural signal in response to a click stimulus ≤85 dB nHL inthe ear(s) to be injected with DB-OTO.

10. Presence of otoacoustic emissions (OAE) in the ear(s) to receive DB-OTO OR

11. Presence of a cochlear microphonic in ears to receive DB-OTO.

12. Willingness of at least 1 parent/legal guardian to consent to vaccinations for thepatient in accordance with the country-specific pediatric immunization schedule

13. No clinically significant laboratory findings on clinical laboratory tests at timeof Screening

14. No evidence that hearing loss is dependent on body temperature

15. From study start and for the duration of the short-term follow-up period (18months): Female patients of childbearing potential and fertile males, must agree touse highly effective contraception. Female patients must agree not to becomepregnant. Fertile male patients must agree not to father a child or donate sperm.

Exclusion Criteria:

1. History or presence of other permanent or untreatable hearing loss conditions.

2. Prior or current cochlear implants in the ear(s) to be injected with DB-OTO

3. History of risk factor(s) for auditory neuropathy not caused by OTOF mutationsincluding: prematurity, low birth weight, hyperbilirubinemia, neonatal intensivecare unit (NICU) admission, and/or low Apgar scores.

4. Prior or current history of malignancies.

5. Prior or current history of meningitis.

6. History of prior treatment with gene therapy.

7. Surgical anatomy that would preclude the planned surgical approach as indicated bymedical imaging (eg, computed tomography [CT] or magnetic resonance imaging [MRI])in the ear(s) to be injected with DB-OTO.

Note: additional inclusion/exclusion criteria apply, per protocol.