Decibel Therapeutics Turns up the Volume on Hearing Loss

Decibel Therapeutics Turns up the Volume on Hearing Loss

By Mary Stuart, Senior Writer/Market Analyst, MedTech Strategist

There are about 466 million people worldwide with disabling hearing loss, 48 million of them in the US. To date, hearing aid devices have been the only solution to sensorineural hearing loss, the kind that comes from aging and the dam­age loud sounds cause. Eyeing the potential blockbuster opportunity, pharmaceutical companies like Decibel Therapeutics have finally joined the fray.

  Dave Grohl, Foo Fighters

Dave Grohl, Foo Fighters

At a recent Foo Fighters concert, lead singer Dave Grohl told the audience, “You will leave deaf, but you will leave happy,” and that wasn’t far from the truth. Loud sounds contribute to hearing loss (aging is the other main cause), which affects 48 million Americans to some degree in one or both ears. 

It is somewhat surprising that there is only one solution for the majority of people with hearing loss—hearing aids—given that hearing is such an individual sense. (A smaller number of people with profound hearing loss in both ears are eligible for cochlear implants). People experience hearing loss differently, have unique patterns in terms of the time they spend in different sound environments, and the underlying mechanisms of disease might be different from one individual to another.

Nevertheless, today, there is basically only the one answer, and it’s not a complete one. The majority of the hard of hearing don’t wear hearing aids, for reasons that we discuss in our recent MedTech Strategist article on hearing aids, hurdles that medical device companies are addressing with new technologies and new business models. 

The opportunity has not gone unnoticed by the pharmaceutical industry, where, at present, there are no drug therapies for treating or preventing hearing loss, nor by some enthusiastic investors that, since 2017, have poured about $150 million into biopharma start-ups focusing on hearing loss (see Figure 1).

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Decibel Therapeutics.jpg

One of these is Decibel Therapeutics Inc., which, like most companies founded by Third Rock Ventures, began, in October 2015, with the identification of an unmet clinical need and a team of thought leaders dedicated to the problem, as well as a $52 million Series A round.

Third Rock partner and chief technology officer Craig Muir recruited founders Charles Liberman, PhD (Harvard Medical School and Massachusetts Eye and Ear); Gabriel Corfas, PhD (Kresge Hearing Research Institute, University of Michigan), Ulrich Müller, PhD (Johns Hopkins) and Albert Edge, PhD (Harvard Medical School and Massachusetts Eye and Ear) to contribute their expertise and keep their ears to the academic ground to mount a multi-modal attack on hearing loss, tinnitus, balance disturbances due to inner ear disorders, and to find ways to prevent hearing loss.

Paula Cobb, Decibel’s Executive VP of Corporate Development, notes that disorders of the ear were, until recently, one of the last untouched territories in the pharmaceutical realm. The human auditory system “is a phenomenally complex system that hasn’t really been studied and broken down to the level necessary to develop drugs,” she says, and that’s because the cochlea has been difficult to study. It’s an extremely small organ locked within the temporal bone, one of the hardest bones in the body. But the tools of genetics, genomics, and different kinds of microscopy now enable researchers to get a glimpse of the cochlea, even though it’s locked away. 

Decibel distinguishes itself from other newcomers in the breadth of its approach. It will develop small molecules, gene therapies, and biologics, using all of the tools of modern drug discovery. “We are looking at all aspects of the ear,” Cobb says, noting that the company’s research has already doubled the number of known and distinct cell types in the ear, and is following many pathways to drug discovery. “We have been developing an understanding of what happens when those cell types are damaged by different kinds of insults like noise, aging, or chemotherapeutic drugs like cisplatin,” Cobb says.  

For example, there is the nerve and synapse hypothesis. A lot of hearing biology has been focused on outer hair cells, which are responsible for amplifying sound, but Charles Liberman’s work is studying the nervous system component of the ear, and his work has shown that synapses are among the first elements damaged in patients with hearing loss.

 
“Decibel’s lead candidates—two small molecule drugs that have entered into clinical trials—will focus on auditory damage due to drug toxicity.”
 

The company’s first programs include two small molecule drugs, gene therapies, and biologics. The lead candidates—two small molecule drugs that have entered into clinical trials—will focus on auditory damage due to drug toxicity. As noted, the cancer drug cisplatin is known to cause cell damage leading to hearing loss, as are aminoglycoside antibiotics. This is an excellent starting point, according to Cobb, because Decibel has a chance to administer its drug candidate before patients take one of those ototoxic drugs to see if it protects hearing. “These are well-defined clinical populations,” she says, noting that studies measuring the effect of a therapy on noise-induced or age-related hearing loss would be more complex to do.

Coming up behind the lead compounds are gene therapeutics, where the company is identifying defective genes, determining which ones it is feasible to treat, and how to deliver them with the appropriate vector to target specific cell types.

As a brand new pharmaceutical target, therapies for hearing loss will evolve from the general to the specific, just as cancer has. “We used to speak of Cancer. It was one thing. Then it became cancer of a certain part of the body, and now it is typed by its genetic origins. Hearing is on the same kind of journey from ‘I can’t hear you’, to ‘I have a specific type of damage to my ear, and I can take this kind of medicine to fix it.’ It will be defined by the genetic component and the nature of the insult and damage to certain cell types in your ear.” There is a lot to be done, she acknowledges, “but progress is happening rapidly.”

Until we get there, however, please be advised to wear ear protection at your next rock concert.

Have comments on this post, or suggestions for topics you’d like us to cover in the Community Blog? Contact blog@medtechstrategist.com.


Further Reading in MedTech Strategist:

  • “Breaking Sound Barriers in the Hearing Aid Market,” By Mary Stuart

  • “Neuromod Devices: Targeting Tinnitus Discretely and Effectively,” By Colin Miller

 

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