Frequency Therapeutics’ FX-322: A Potential Hearing Loss Treatment on the Horizon

For as long as people have experienced hearing loss, they’ve been anxious for better treatments. And although that has remained elusive thus far, for certain types of hearing loss, a significant treatment may be coming before 2030: FX-322, the lead drug candidate from Massachusetts-based biotechnology company Frequency Therapeutics.

I recently spoke with Carl LeBel, PhD, Frequency’s Chief Development Officer, about the company, FX-322 and the potential of regenerative medicine to treat hearing loss (thanks to Suzanne Day, Associate Director of Digital and Corporate Communications, for her assistance). “We think within this decade, hopefully there’s the first hearing restoration therapeutic that’s available,” Mr. LeBel said.

FX-322 and the Formation of Frequency Therapeutics

To understand this potential treatment, it helps to understand the discoveries that lead to the formation of the company. In 2014, the company was founded based on scientific breakthroughs by Jeff Karp, PhD, Professor of Medicine at Brigham and Women’s Hospital, and Bob Langer, ScD, Institute Professor at Massachusetts Institute of Technology (MIT).

The researchers found that some body tissues regenerate much better than others. They studied the lining of the small intestine, which turns over roughly every four days, because it’s designed to absorb and distribute nutrients to other parts of the body. Drs. Karp and Langer saw the molecular pathways that signal the lining’s cells to turn over quickly and form new tissues.

Around the same time, another scientific group found very similar cells in the cochlea – but with one big difference: in the cochlea, these cells weren’t active. They saw that the cochlea’s cells didn’t regenerate and form new sensory hair cells. “So that was the formation of Frequency,” LeBel explains. “And Frequency was asking, why is that the case? Why is it that the cochlea isn’t regenerating cells and the small intestine is?”

This led to the discovery of two small molecules that make up FX-322, which targets these cells, called progenitor cells. Essentially, this process is meant to drive hair cell regeneration: The drug targets pathways to those cochlear cells, and when activated, they divide and form a new cell of themselves, called daughter cells. “And then most importantly, they form a new sensory hair cell,” LeBel says.

Six years after it was founded, the company now has a staff of close to 70 people. FX-322 has cleared phase 1/2 of clinical trials and is now in phase 2a. “That’s sort of the middle phase of clinical development where you’re really trying to characterize the efficacy of your drug,” LeBel explains.

FX-322 Findings So Far

As the company has progressed through clinical trials, they’ve made some interesting discoveries. The participants in the trials have been people with mild to moderately-severe hearing loss. And while FX-322 has a favorable safety profile for all participants, the hearing improvement was seen mostly in the moderate to moderately-severe individuals, as measured by improved word recognition. LeBel speculates that this is because people with more hearing loss have more to gain.

In a separate study, Frequency has found that delivering FX-322 directly into the ear by intratympanic injection effectively reaches the site of action in the cochlea – so it’s going right to the place where it’s needed. The drug candidate can be administered by an ear, nose throat doctor (ENT) in their office. “But importantly, you also don’t have to worry about any systemic side effects that oftentimes are challenging for other drugs, like if somebody’s taking a pill,” LeBel adds.

And in more promising news, individuals who were given FX-322 in 2018 were retested 1-2 years later, and many of them maintained their hearing improvements – which suggests that hearing function is maintained. “And that’s exactly what you want to see when you’re developing drugs to treat a chronic condition,” says LeBel.

Who Might FX-322 Help?

FX-322 is designed to treat what’s referred to as acquired sensorineural hearing loss, which includes forms such as:

• Noise-induced hearing loss
• Sudden sensorineural hearing loss
• Age-related hearing loss
• Ototoxic drug exposure

“All of those forms are associated primarily with a loss of sensory hair cells,” LeBel says. “So we think they can possibly be good candidates for FX-322.”

It should be noted that this likely excludes genetic forms of hearing loss.

Rather than being a full-on cure for all degrees of acquired hearing loss, LeBel says that Frequency sees FX-322 as “a disease-modifying drug,” meaning it may modify hearing loss. “The way we think possibly FX-322 could fit into the hearing-health world is, you could imagine there might be individuals that would be candidates for cochlear implants – you could treat them with FX-322, and it’s possible that you could take them from being a cochlear implant candidate to a hearing aid candidate,” LeBel says. Similarly, people with less severe hearing loss who are hearing aid candidates might not need hearing aids if the drug treatment is successful.

What Frequency Wants Individuals With Hearing Loss to Know

LeBel acknowledges that Frequency is treading completely new territory, and when FX-322 hopefully gets to the market in the coming years, it’s going to take a shift from all of those who deal with hearing loss – either personally or professionally – to integrate the product into the world. That means partnering with patient volunteers, patient advocates, audiologists and otolaryngologists. “All of those groups have to come together and work together for this to be successful. So we just want to tell everybody we want to be part of that partnership,” says LeBel. “We want to do whatever we can to build it and move it forward and support it. And we’re going to be successful if we do it together.”

Want to learn more about Frequency Therapeutics?

• Check out Frequency’s website and press releases
• Read about the FX-322 clinical trials
• Follow Frequency Therapeutics on Twitter and LinkedIn