Audion Therapeutics is a clinical-stage biopharmaceutical company focused on developing treatments to address hearing disorders. Its primary mission is to pioneer regenerative therapies for hearing loss, a field historically dominated by mechanical or prosthetic devices. The company aims to create pharmaceutical solutions that can restore hearing function by targeting the underlying biological causes of impairment.
The Biological Target for Hearing Restoration
Sensorineural hearing loss (SNHL) is the most common type of hearing impairment, affecting millions globally due to factors like aging and noise exposure. This condition results from damage to the structures of the inner ear. At the center of this damage is the loss of sensory hair cells within the cochlea, the spiral-shaped cavity of the inner ear. These microscopic cells are responsible for converting sound vibrations into electrical signals that the brain interprets.
These hair cells function much like the bristles of a microphone, capturing sound information and transmitting it to the brain via the auditory nerve. When these cells are damaged or die, they do not naturally regrow in humans, leading to a permanent decline in hearing. The inability of the human body to replace these cells is the challenge that Audion’s research seeks to overcome.
Mechanism of Regenerative Therapy
Audion Therapeutics is focused on a regenerative strategy that uses small molecules to awaken the inner ear’s dormant regenerative potential. Their approach centers on inhibiting a specific cellular communication system known as the Notch signaling pathway. In the cochlea, this pathway is responsible for keeping certain cells, called progenitor or supporting cells, in a quiet state, preventing them from developing into new sensory hair cells. These supporting cells exist alongside hair cells and have the latent ability to become new ones.
The company’s therapeutic candidates are classified as gamma-secretase inhibitors (GSIs). By administering a GSI, the therapy blocks the Notch pathway’s “off” signal. This inhibition is designed to allow the existing progenitor cells within the cochlea to transform, or differentiate, into new, functional hair cells.
This process relies on stimulating the body’s own resident cells rather than introducing foreign stem cells. The therapeutic is delivered through an intratympanic injection, which sends the drug directly through the eardrum to the inner ear. This local delivery method maximizes the drug’s concentration at the target site while minimizing its exposure to the rest of the body.
Clinical Development Status
Audion’s leading drug candidate, LY3056480, licensed from Eli Lilly, has been the subject of clinical trials to assess its safety and effectiveness. The company, in partnership with the REGAIN consortium, completed a Phase 1/2a trial for its GSI treatment. The Phase 1 portion of the study established the safety and tolerability of the treatment when administered via intratympanic injection. Fifteen patients with SNHL participated in this initial safety phase in the United Kingdom.
While the trial did not meet its primary goals for hearing improvement across all participants, a deeper analysis showed encouraging signs. Some patients demonstrated improvements in hearing tests, including the ability to understand speech in noisy environments, for up to 12 weeks after treatment. These findings have prompted Audion to plan for further development with a refined study design.
Comparison to Existing Hearing Solutions
The regenerative therapy being developed by Audion Therapeutics offers a fundamentally different approach compared to current hearing solutions. The most common treatments today are hearing aids and cochlear implants, both of which are prosthetic devices that assist with hearing but do not repair the underlying biological damage.
Hearing aids work by amplifying sound, making it louder and easier for the remaining healthy hair cells to detect. However, their effectiveness diminishes as more hair cells are lost, and they often perform poorly in noisy settings, which is a major challenge for users. Cochlear implants, on the other hand, are designed for more severe hearing loss. They bypass the damaged hair cells entirely, using electrodes to directly stimulate the auditory nerve, which then sends signals to the brain.
In contrast, Audion’s goal is not to amplify or bypass but to rebuild. Their gamma-secretase inhibitor aims to regrow the sensory hair cells themselves, which could potentially restore the ear’s natural ability to process sound. If successful, this approach could offer a more nuanced and organic hearing experience than what is possible with current mechanical and electronic devices.