BioPharma, Startups

Two biotech startups tackle hearing loss

Their efforts will most likely not reach the clinic before late 2018, but the two companies have a lot of motivation.

Microscopic image of hair cells and their progenitors.

Modern life is bad for hearing. Industry, traffic, construction, headphones and even antibiotics take a toll. To mitigate the problem, patients rely on assistive devices: hearing aids to amplify signal or cochlear implants to bypass damaged hair cells. Pharmacological interventions just don’t exist.

But now, two emerging biotechs, Frequency Therapeutics and Decibel Therapeutics, are developing drugs to remedy hearing loss. These efforts will most likely not reach the clinic before late 2018, but the companies have a lot of motivation. According to the World Health Organization, around 360 million people face disabling hearing loss. Millions more have less severe issues.

“It’s noise pollution,” said David Lucchino, president and CEO at Frequency, said in a phone interview. “There was a great study about people who were born and spent their lives on Easter Island and people who left. The people who stayed had great hearing well into their 60s. The people exposed to noise pollution had the same kinds of hearing loss we see every day.”

Based in Cambridge, Massachusetts, Frequency is developing molecules that stimulate progenitors, the immature cells that can differentiate into healthy tissues.

“We’re born with around 15,000 hair cells and they move to tell our brains we’re hearing sound,” said Chris Loose, Frequency’s chief scientific officer. “They die off when there’s too much noise pollution. What if we could make a small molecule drug that activates progenitors, restores hair cells and restores hearing?”

The proof of concept, in part, came from a Nature Methods paper that studied intestinal progenitor cells. The research was led by MIT’s Robert Langer and Harvard’s Jeffrey Karp. Langer is on Frequency’s board of directors and they are both on the company’s scientific advisory board.

Less than a mile away from Frequency, Decibel is working on the same problem but taking a more wide-ranging approach. Backed by Third Rock Ventures, that company is also looking for ways to restore inner ear function, perhaps using small molecules, antibodies, siRNAs or other approaches.

But, according to Decibel President and CEO Steven Holtzman, the other important goal is to understand why people lose their hearing.

“You go to any major cancer pharmaceutical company, they have a discovery and translational medicine platform to do cancer drug discovery,” said Holtzman. “But that doesn’t exist anywhere in the world of hearing.”

Decibel is working to create that comprehensive platform, developing animal models and organoid systems, as well as advancing audiometric, electrophysiological and other diagnostic approaches. They want to understand the natural history that drives different types of hearing loss. For example, the antibiotic tobramycin is often prescribed to cystic fibrosis patients with respiratory infections.

“You have two CF patients,” said Holtzman. “One gets two doses and loses their hearing. The other is on it for a year and has no problems. How do we understand the difference?”

The company is testing a number of potential drug candidates for drug- and noise-induced hearing loss, genetic conditions and tinnitus. But they also want to develop agents that protect people, helping the ear bud generation retain their hearing. Holtzman believes the Decibel platform will ultimately produce a steady stream of therapeutics.

“The first drugs won’t be the best drugs,” said Holtzman. “As we get a better understanding, we’re going to get better drugs. You’re only going to do that if you build a discovery and translational medicine platform.”

Image: Frequency Therapeutics