Hearing loss, which affects millions of Americans with no effective drugs to fight it, has become a ripe field for biotech investment. The latest example is Frequency Therapeutics, which sprung from MIT earlier this year and has just corralled a big round of funding.
The Woburn, MA-based startup has raised a $32 million Series A led by CoBro Ventures, an investment firm formed by tech entrepreneur Marc Cohen and his brother Alain.
People lose their hearing for a variety of reasons, from age to loud noises. According to the Hearing Health Foundation, nearly 50 million Americans and 360 million worldwide have hearing loss. Hearing aids and cochlear implants are effective in some cases, but they don’t work for everyone.
Frequency is one of several new companies racing to develop the first approved drug for hearing loss, now a possibility with deeper understanding of the biology of the inner ear. “I’m incredibly excited that after 40 years at the bench doing basic science it looks like some of our ideas are going to be taken from bench to bedside,” M. Charles Liberman, a Harvard Medical School otology professor, told Xconomy in 2015.
Liberman is also a scientific founder of Decibel Therapeutics, a Boston startup that raised $52 million from Third Rock Ventures and SROne in 2015 and, like Frequency, aims to combat hearing loss. Other companies are much further along. Otonomy (NASDAQ: OTIC), has a drug for swimmer’s ear that could be approved this year and a second for Meniere’s disease, a fluid imbalance of the inner ear, in Phase 3 testing. Auris Medical (NASDAQ: EARS) failed a Phase 3 trial in tinnitus but has late-stage tests underway for other hearing loss conditions. (Check out this story from Chemical & Engineering News for a detailed look at the field).
With its new round of cash, Frequency aims to advance research from biomedical engineers Bob Langer (MIT) and Jeffrey Karp (Harvard Medical School). The two teamed with others in February to publish a paper in Cell Reports about potentially regenerating hair cells in the inner ear, which, if proven successful in further testing might help people regain lost hearing.
The idea is to activate what are known as “progenitor” cells, which generally lie dormant but can morph into certain other types of cells. Progenitor cells might combat hearing loss if they can be manipulated to create new inner ear hair cells (pictured), which pick up sounds and convert them to electrical impulses. People lose their hearing because hair cells are damaged or killed; they don’t come back. “The hair cells that you are born with are the ones you die with,” says CEO David Lucchino.
Academic groups have been trying for years to regenerate hair cells therapeutically. There are no approved therapies yet, but some groups have made significant strides. Gene therapy, for instance, a method of delivering a long-lasting genetic fix for a disease, is finally being tested in humans to treat genetic forms of hearing loss. Swiss firm Novartis and its Gaithersburg, MD, partner GenVec (NASDAQ: GNVC) began the first trial in 2014 (the study is still ongoing). Several studies have been published this year alone on gene therapy tests in animals conducted at Harvard, Johns Hopkins University, and other academic institutions.
Frequency wants to regenerate hair cells by a different method: using small-molecule drugs that can coerce progenitor cells into making new hair cells. In the Cell Reports paper, Langer, Karp, and others showed that, in preclinical tests, progenitor cells expressing a protein called LGR5+ could produce new healthy hair cells when stimulated with drugs. Langer, Karp, and team describe using a “cocktail” of drugs and growth factors, each of which block specific enzymes. The drugs in the mix have been tested in clinical experiments for other diseases, but not in combination for this use.
“It’s an exciting first step,” says Alan Cheng, a pediatric otolaryngologist and researcher at Stanford University Health Care in Palo Alto, CA who isn’t involved with Frequency.
Frequency believes an injection into the ear will help produce enough hair cells to restore hearing. “Our small molecules are giving a therapeutic push to kick-start the process,” Lucchino says. Then “the innate biology takes over.”
Lucchino won’t say whether the drugs the company plans use are the same as those described in the Cell Reports paper, or how long the effect is intended to last. The first human studies should begin in a year.
Looking at Frequency’s preclinical results, Cheng notes that the company’s tests on young mice got a “very robust response” but weren’t as successful with adults. Frequency will have to the same impact on mature organs.
“Is it true that they have found a combination and they’re just one or two steps away?” Cheng says. “That’s probably what most people will want to find out.”
Frequency is initially targeting chronic noise-induced hearing loss—younger people who lose their hearing because of exposure to harmful noise—before branching out into other fields. The Centers for Disease Control estimates that about 5.2 million children aged six to 19 and roughly 26 million adults from 20 to 69 years old have suffered permanent damage to their hearing from excessive noise.