Hearing Loss Programs

Hearing loss is a large and growing unmet need with estimates by the World Health Organization that more than 360 million people worldwide have disabling levels of loss. This leads to social isolation, lower quality of life, and higher rates of dementia and depression. Common causes include aging, noise, exposure to ototoxic drugs, and genetics, with increased noise exposure from use of recreational music devices accelerating the onset of hearing loss. The pathologies of hearing loss typically involve damage to hair cells and/or spiral ganglion neurons in the inner ear.

We are advancing three distinct hearing loss programs targeting different pathologies: repair of synaptopathy for treatment of hidden hearing loss (OTO-413), protection of hair cells from ototoxic drugs including cisplatin chemotherapy (OTO-5XX), and hair cell regeneration for treatment of severe hearing loss (OTO-6XX).

OTO-413 (BDNF)

OTO-413 is a proprietary, sustained-exposure formulation of brain-derived neurotropic factor (BDNF) which is a naturally occurring protein involved in neuron growth and repair. Nonclinical studies by Otonomy and other research groups have demonstrated that local administration of BDNF repairs ribbon synapses damaged due to noise trauma or exposure to ototoxic chemicals and restores hearing function. We have initiated nonclinical testing and manufacturing for OTO-413 to support an Investigational New Drug (IND) Application, with a Phase 1/2 clinical trial expected to begin in hearing loss patients in the first half of 2019. The initial indication for OTO-413 will be patients with hidden hearing loss, a synaptopathy-related hearing loss characterized by speech-in-noise hearing difficulty. This condition affects nearly 3% of the U.S. population1.


OTO-5XX is an otoprotectant in development for the prevention of cisplatin-induced hearing loss (CIHL). A number of drug classes cause ototoxicity including platinum-based chemotherapeutic agents and aminoglycosides. We established feasibility of conducting clinical trials in patients undergoing cisplatin chemotherapy through a small Phase 2 trial with OTIVIDEX in pediatric patients. We have identified a therapeutic target that offers a higher level of otoprotection than steroids based on nonclinical proof-of-concept studies, and are evaluating molecules in this class. Selection of a candidate for clinical development is expected to occur in the second half of 2018. The initial indication for OTO-5XX will be the prevention of CIHL, which is relevant for approximately 500,000 patients in the U.S. who are treated each year with platinum-based chemotherapies.


OTO-6XX induces hair cell regeneration and is being developed for the treatment of severe hearing loss. Considerable interest and attention has been focused by otology researchers over the past several decades for ways to regenerate hair cells as an approach to treating severe hearing loss, which is estimated to affect 6.6 million people in the U.S.2 This effort has included extensive research with non-mammalian species that are capable of hair cell regeneration in order to identify pathways for therapeutic intervention. Targeting one of these pathways, we have demonstrated regeneration of hair cells in a nonclinical proof-of-concept model using a class of small molecules. Selection of a candidate for clinical development is expected to occur in the second half of 2018.

1Tremblay et al., Ear Hear (2015)
2Goman and Lin, Am J Public Health (2016)