Gene Therapy and the Future of Hearing Healthcare: Interview with Akouos CEO, Manny Simons

gene therapy hearing loss treatment
Hearing Health & Technology Matters
August 7, 2020

Hearing Healthcare 2020 is a column where we explore the forces behind the changing landscape and disruptions impacting the hearing healthcare industry. 

This week, HHTM President and CEO, Kevin Liebe, interviews Dr. Manny Simons, CEO, President, and Co-Founder of Akouos. His company, which recently went public, raised over $200M in its initial public offering (IPO) in June of this year. Akouos’ lead program, AK-OTOF, is a gene therapy focused on restoring hearing in individuals with sensorineural hearing loss due to mutations in the otoferlin (OTOF) gene.

KL: Can you provide readers with some of your background and how you got interested in treating hearing loss?

MS: I grew up in a musical home and began playing instruments as a child. I believe this connection to music from an early age taught me to appreciate the richness of sound and the power of sound to communicate. Throughout high school and college, my connection to music grew deeper, as I sang and played trumpet in ensembles while continuing to play solo piano.

Throughout my early education, I grew passionate about both neuroscience and music, and I was fascinated by the pioneers in each of these areas. My undergraduate research thesis focused on trying to bring these two worlds together – working to better understand how the ear converts air vibrations into a signal our brain interprets as sound. Through this work, I fell in love with the biology of hearing. 


KL: Over the past few years, we’ve seen a number of startups and biotech companies becoming involved in treating hearing loss, including several now focusing primarily on gene therapy. What do you attribute this sudden interest to?

MS: I think the increased attention is driven by three factors: (1) the high unmet need and impact that hearing loss has on individuals and those around them; (2) the scientific progress in recent years that has elucidated the underlying mechanisms of hearing loss, particularly genetically-driven hearing loss; and (3) the compelling clinical data generated by AAV gene therapies in other therapeutic areas and recent FDA-approval of the first in vivo gene therapies.  

There is growing awareness that hearing loss is one of the largest unmet needs in medicine. Approximately 466 million people around the world, including 34 million children, live with disabling hearing loss. Hearing loss in children is recognized as a potential developmental emergency, and hearing loss later in life has recently been identified as a major risk factor for dementia. Despite the impact hearing loss can have on individuals and their interactions with those around them, there are still no pharmacologic therapies approved to treat hearing loss.  

Only relatively recently has the role of genetics in hearing loss begun to be appreciated. It is now estimated that approximately 80% of hearing loss in infants has a genetic cause, and the hearing research community has identified over 150 genes in which mutations can lead to deafness. Many of the recent advances in gene therapy for disorders of the eye and central nervous system can potentially be applied to genetic disorders of the inner ear. 

Akouos itself was founded by leaders in the fields of neurotology, genetics, inner ear drug delivery, and AAV gene therapy. This group of researchers have been working towards the goal of advancing the science and understanding of hearing loss that will hopefully be able to bring advances to these patients and their families.  


KL: What makes Akouos’s approach to hearing loss treatment unique/different?

MS: The options that exist today for hearing loss do not treat the underlying cause of the disease.  Akouos’s mission is to develop gene therapies with the potential to restore, improve, and preserve high-acuity physiologic hearing for individuals living with disabling hearing loss worldwide.

We are solely focused on potentially one-time gene therapies in hearing loss. We’re doing this by building a precision genetic medicine platform that incorporates a proprietary vector library and a novel delivery approach. We aim to become a fully integrated biotechnology company, working to advance potential new therapies from discovery, through clinical development and approval, so that we can deliver new options to patients.

I believe our platform and our team together provide a unique advantage to efficiently develop potential genetic medicines for a variety of inner ear disorders.


KL: Assuming your lead candidate AK-OTOF becomes an approved treatment option in the future, how would you envision the patient journey occurring from diagnosis to treatment?

MS: Our AK-OTOF program is in the preclinical research phase right now. We plan to submit an Investigational New Drug (IND) application, required to begin our clinical trial, in the second half of 2021.

As we work to advance this potential therapy through clinical development, our aim is to provide an option for future patients to restore physiologic hearing. In the US and in many countries around the world, a diagnosis starts with newborn hearing screening.

Today, 97% of newborns in the United States have their hearing screened, and most individuals with severe to profound congenital hearing loss in the United States are identified shortly after birth. Hospitals typically use either auditory brainstem response (ABR) or otoacoustic emission (OAE) testing to identify hearing loss in newborns. ABR testing reflects how the cochlea, auditory nerve, and auditory pathways in the brain are working. OAE testing reflects whether outer hair cells in the cochlea respond to sound.

Individuals with severe or profound sensorineural hearing loss do not benefit from hearing aids. As a result, families who have a child born with severe or profound hearing loss have two options for intervention: a cochlear implant, which involves an invasive surgery to implant a chronic, indwelling device; and/or introduction of nonverbal language, such as American Sign Language. The approval of a gene therapy would add a third option for some children. Our hope is that AK-OTOF will demonstrate an ability to restore high-acuity physiologic hearing in children who are born deaf due to mutations in the otoferlin (OTOF) gene.

In the coming years, genetic testing will play an increasingly important role in the diagnostic journey of children with hearing loss. There are already multiple comprehensive hearing loss gene panels with the potential to diagnose dozens of forms of genetic hearing loss. I think the rate of genetic testing in children with hearing loss will continue to increase, and will eventually become part of universal newborn screening.


KL: Whether it’s a pharmaceutical, gene therapy-based, or some other approach, do you believe we will have an FDA approved therapeutic treatment option for sensorineural hearing loss in the next 5 years? Why or why not?

MS: Akouos and other companies are working with urgency to bring new options to those living with disabling hearing loss around the world. Given the amount of research and resources being committed to hearing loss today and in recent years, I do think there is a possibility for an FDA-approved therapeutic in the next 5 years, but of course we cannot guarantee that this milestone will be achieved given the uncertainties of clinical timelines.

It is an exciting time for the field, and we’re going to work hard to translate this potential into therapies that can have a meaningful impact on the lives of millions of individuals and their loved ones.


KL: Akouos recently filed an IPO, and saw a huge level of interest in your company, raising more than twice your original IPO funding goal. Will this allow you to accelerate or expand your original plans?

MS: I’m very proud of our team and how much they have accomplished over the past few years to get to this point. But we have a lot of work to do before we succeed in making new therapies available for patients. Our successful IPO helps provide the financial resources we will need to achieve this goal.

Proceeds from the IPO will fund our clinical trials, additional research and development for an expanded pipeline of potential new medicines, and expand our manufacturing capabilities.


KL: Thanks for sharing your views with us today and providing us with an update on the progress Akouos is making towards developing a gene therapy treatment for hearing loss.

MS: Thanks so much for the opportunity to share what we’re doing at Akouos.


Manny Simons, Ph.D., CEO, President, and Co-Founder of AkouosDr. Simmons is a scientist and entrepreneur with over fifteen years of experience in hearing science research and new venture formation. Prior to founding Akouos, Dr. Simmons held leadership roles in business and corporate development at Voyager Therapeutics and WarpDriveBio, where he was instrumental in leading strategic partnerships with aggregate value exceeding $1 billion. Earlier in his career, Dr. Simons was an Entrepreneurial Fellow at Flagship Ventures, where he was a member of the founding team of Seres Therapeutics. Dr. Simons earned an A.B. magna cum laude in Neuroscience and Music from Harvard College; a Ph.D. in Biomedical Engineering from MIT under Professor Robert Langer; and an M.B.A. from Harvard Business School.


Kevin Liebe, AuD, is President and CEO of Hearing Health & Technology Matters (HHTM). An experienced clinician, Kevin has practiced in a wide range of settings, including private practice, hospital and ENT settings, as well providing clinical education and training for a major hearing aid manufacturer. He is a past president and board member of the Washington State Academy of Audiology and has served as an expert audiology consultant and advisor to hearing technology startups and investors

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