Hearing loss can stem from a variety of reasons, but in rare cases it’s caused by genetic defects. Akouos is developing a gene therapy to address these problems and it’s planning an IPO to finance the first tests of its approach in humans.
In paperwork filed with regulators late Friday, Boston-based Akouos set a preliminary $100 million goal for its IPO.
The first target for Akouos is hearing loss due to mutations in the OTOF gene, which encodes a protein called otoferlin. Hearing happens when tiny hair cells in the inner ear pick up vibrations and turn them into signals that the brain interprets as sound. Otoferlin is key to this process, as it enables the sensory cells of the ear to release tiny membranes carrying neurotransmitters, Akouos says in its filing. These neurotransmitters activate auditory neurons, which in turn relay the information to the brain where it is recognized as sound.
Those who have OTOF gene mutations are typically born deaf. There are currently no FDA-approved therapies for this form of hearing loss. The experimental Akouos gene therapy, AK-OTOF, is intended to deliver a functioning version of the OTOF gene with the goal of restoring proper otoferlin expression.
The Akouos therapy is delivered using an engineered version of adeno-associated virus (AAV), an approach used by some FDA-approved gene therapies marketed by other companies for other diseases, as well as for some gene therapies still in development. But the anatomy of the inner ear presents challenges for AAV gene therapy delivery, the company says in its filing. Also, AAV has a limited capacity for carrying a genetic payload.
To overcome those limitations, Akouos uses synthetic AAVs that recreate naturally occurring viruses called ancestral AAVs, which the company says can reach the target in the ear. Furthermore, the company uses a “dual vector” approach that employs two engineered viruses, each carrying a fragment of the OTOF gene. The Akouos approach to gene therapy is based on the research of Luk Vandenberge, director of the Grousbeck Gene Therapy Center in Boston and a professor at Harvard Medical School. In mouse studies, Akouos says AK-OTOF delivered its genetic payload to the inner ear hair cells, restoring auditory function. Now the company wants to test its technology in humans.
Paperwork seeking FDA permission to start a clinical trial is on track to be submitted in 2021, Akouos says in its filing. If all goes as planned, the company expects to report preliminary data from the clinical trial the following year.
Akouos isn’t the only company developing new treatments for inherited forms of hearing loss. Decibel Therapeutics is also developing a gene therapy to address the same genetic protein deficiency that Akouos is targeting. The Boston-based company’s experimental gene therapy, DB-OTO, is in preclinical development with partner Regeneron Pharmaceuticals (NASDAQ: REGN). Otonomy (NASDAQ: OTIC), in San Diego, is advancing a preclinical gene therapy program intended to address hearing loss caused by mutations in another key gene, GJB2. Frequency Therapeutics (NASDAQ: FREQ) is addressing hearing loss caused by the loss of hair cells in the inner ear. The Woburn, MA-based company is developing a regenerative medicine approach that coaxes the regrowth of these hairs.
Akouos was founded in 2016 and unveiled $50 million in financing two years later. In March, the company closed a $105 million Series B round of financing that added crossover investors. The biggest shareholders in Akouos prior to the IPO are 5AM Ventures and New Enterprise Associates, which own about 21.6 and 18.5 percent respectively, according to the filing.
Akouos has applied for a listing on the Nasdaq under the stock symbol “AKUS.” If the company successfully completes the IPO, it says it will apply the capital toward clinical development of AK-OTOF, as well as the preclinical development of other programs in its pipeline.