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Repairing hearing with meds

July 29, 2017

In any bustling city street, in the middle of the afternoon, it’s probably the case that half or more people are wearing earbuds, while the rest are abiding the noise pollution all around them. No one thinks twice about it, either.

The reality is that from a very young age, our hearing is now under assault. Little wonder that one in eight people in the United States aged 12 years or older has hearing loss in both ears, based on standard hearing examinations. By age 65, one in three people has hearing loss.

The problem will only grow as more people flock to city centers. According to recent United Nations data, roughly 54 percent of the world’s population lives in urban areas right now, and that number is expected to hit 66 percent by 2050, meaning cities could take in another 2.5 billion people, accounting for population growth.

With any luck, in our lifetimes, potentially soon, even, some of this hearing loss will be fixable — not with hearing aids or cochlear implants, which aren’t available to everyone and don’t work for a high percentage of people anyway. Scientists think instead that the combination of human genetics and single cell expression profiling has brought us to the point where medicine can help fix hearing. In fact, there are right now a small number of outfits quietly racing to develop the first approved drug for hearing loss, and if, like us, you live with a playlist unspooling in your ears part of each day, you should be rooting for them to succeed.

Some are further along than others, as a recent Xconomy piece observed. San Diego-based Otonomy has a drug for swimmer’s ear that could be approved this year. Meanwhile, Auris Medical, a Swiss biotech whose tinnitus candidate last year failed to beat a so-called dummy therapy in a Phase 3 trial, is currently working on other hearing loss conditions.

Both Otonomy and Auris Medical are publicly traded, but they have peers (and rivals) in the still-private world. Two young startups to watch — they have strong founders and top venture backing on their side — are Frequency Therapeutics and Decibel Therapeutics, both based in Boston.

Decibel Therapeutics was incubated by the powerhouse investment firm and incubator Third Rock Ventures. Along with SROne (a venture fund that counts GlaxoSmithKline as its sole investor), Third Rock provided the company with $52 million to get started in 2015, and it more recently raised an undisclosed amount of funding from GV.

Anthony Philippakis, a venture partner at GV who led the deal, says one aspect of Decibel that excited him is its portfolio approach, with some of its focus on single cell genomics, some on human genetics, some on direct-to-patient clinical trials and some on generating phenotypic data about the hearing system. (Philippakis seems to have embraced a portfolio approach to his own work. In addition to working with GV, he’s a cardiologist at Brigham and Women’s Hospital, and the chief data officer at Broad Institute of Harvard and MIT.)

As Decibel’s CEO, Steve Holtzman explains of the company’s modus operandi: “If you make investments in a broad discovery and translational medicine platform for drug discovery — not just take a shot on goal with a single drug or assay — you have a better chance to dominate the space.”

Indeed, Holtzman — who is focused first on hearing loss in millennials but who has ambitions to tackle hearing loss across the age spectrum — says Decibel is working on “drugs to reduce against drug toxicity [which can cause hearing loss], drugs to repair hair cells [in the inner ear] , drugs that are looking at other aspects of hearing that may involve the [central nervous system], and drugs focused on regeneration [versus just cellular repair].”

Our play is “much broader” than that of any other firm, adds Holtzman, who has worked in the biotech industry for roughly 30 years and helped co-found the company with Third Rock.

Holtzman doesn’t mention Frequency Therapeutics specifically, but it’s probably no coincidence that Frequency — which recently raised $32 million in Series A led by CoBro Ventures, an investment firm formed by tech entrepreneur Marc Cohen and his brother Alain — is taking a rather different approach.

The vision for the company started three years ago, says CEO David Lucchino. Bob Langer, a renowned biomedical engineer at MIT, had teamed up with peer Jeffrey Karp of Harvard Medical school on research showing that cells in the inner ear — they’re called progenitor cells, and each of us is born with a fixed number of them — could potentially be manipulated to create new inner ear cells.

Why that’s important: these inner ear hair cells absorb sound and convert it to electrical impulses.

Frequency’s lead program is focused on treating chronic hearing loss by regenerating cochlear hair cells with combinations of easily made drug molecules. But one challenge, among many, is whether this growth can happen in vivo. Why no one yet knows: Langer and Karp’s earlier findings involved human cochlear tissue that had been removed from a 40-year-old, who’d had to have it removed in order for surgeons to get to a tumor.

Though the researchers witnessed an encouraging response from the tissue after dosing it with drugs, shooting medicine directly into someone’s ear and getting it to grow new cells is a giant leap from that starting point. Lucchino acknowledges, too, that determining what amount of “medicine” to inject, or how often to inject it, would present a whole new host of other obstacles to overcome.

Given the various unknowns, it’s perhaps no surprise that Lucchino — who worked as a venture capitalist with Polaris Partners before founding an earlier biosciences company 10 years ago — says Frequency plans to focus on more than hearing eventually.

“It’s our first focus, but we view ourselves as a next-generation regenerative medicine player. And hearing is a wonderful place for us to start.”

Either way, Frequency might find encouragement in other initiatives that are making meaningful strides. For example, two projects similarly involving endogenous cells (meaning already present in the body), are now in clinical development at the Swiss company Novartis.

The programs — which came out of the small-molecule regenerative program of Scripps Research Institute of La Jolla, Calif. — are focused on other areas, including treating multiple sclerosis and gastrointestinal problems. Some academics see the approach as potentially very powerful, however. If only it works. Stay tuned.

http://tcrn.ch/2veFOCM

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