Decibel Therapeutics Strikes a Balance, Adding Regenerative Med Focus

Xconomy Boston — 

Decibel Therapeutics emerged four years ago aiming to build a pipeline of medicines for various forms of hearing loss. One of those drugs is in the clinic. Others were shelved. And some of the company’s resources are now focusing on regenerative therapies addressing the inner ear.

The recent pipeline changes are accompanied by a corporate shakeup. Steven Holtzman is retiring as CEO, and has been replaced by acting CEO Laurence Reid, an entrepreneur-in residence at Third Rock Ventures, one of the investors in Boston-based Decibel. Reid says this “modest restructuring” means that some employees were laid off. He declined to say how many.

“We feel the need to focus our efforts,” he says. “We’re clear about where we think the best opportunities are for our technology.”

Decibel’s lead drug, DB-020, is being developed as a way to prevent hearing loss in cancer patients treated with cisplatin. Deafness is one of the side effects associated with that chemotherapy. That drug is intended to protect cells involved in hearing from the toxic effects of chemotherapy. It’s currently in Phase 1b testing. Another pipeline candidate, DB-OTO, is being developed to treat congenital deafness. The gene therapy is meant to restore production of otoferlin, a protein that is key for the hair cells located in a part of the inner ear called the cochlea. These hairs turn vibrations into the electric signals picked up by the auditory nerve.

In addition to its hearing loss treatments, Decibel is now also talking about its research in balance disorders. A different part of the inner ear, the vestibule, houses hair cells that detect motion, rotation, and velocity. Like the hair cells of the cochlea, the vestibular hairs can be lost as people age or as a side effect of drugs, says Joe Burns, Decibel’s head of biology. Also like the cochlear hairs, once lost they don’t grow back.

The most advanced Decibel balance disorder drug, DB-201, is intended to coax new vestibular hair cell growth. The first target is bilateral vestibulopathy, which causes patients to experience dizziness and unsteadiness stemming from damage to the inner ear. The gene therapy, administered by a local injection to the inner ear, employs adeno-associated virus, a viral delivery system currently used by some gene therapies, to reach its target and kick start hair cell growth.

“When you lose these hair cells, there’s another population of cells that stick around and they’re a source for generating new hair cells,” Burns says. “They just need to be stimulated.”

That’s a different approach than the regenerative medicine technology being developed by Frequency Therapeutics (NASDAQ: FREQ). The Woburn, MA-based company uses small molecules to activate progenitor cells in the inner ear with the goal of coaxing new hair cell growth. Frequency’s lead drug, FX-322, is expected to report preliminary data from a Phase 2a study in the second half of this year.

Meanwhile, DB-201 is preclinical. The gene therapy is being developed under a partnership with Regeneron Pharmaceuticals (NASDAQ: REGN), which is also an investor in Decibel. Regeneron is funding some of the research, and Decibel stands to earn milestone payments depending on the progress of that program and others covered by the partnership. Under the deal, Decibel is leading clinical development and will retain commercial rights if the therapy reaches the market. If the partnered programs are commercialized, Decibel will share the revenue with Regeneron.

Decibel is also positioning itself to develop more regenerative medicines for the ear. It has an option agreement for technology developed at Rockefeller University. Scientists there have discovered small molecules that target a signaling pathway that plays a key role in regulating tissue regeneration and the proliferation of cells in the ear needed for hearing and balance.

Decibel’s added emphasis on regenerative therapies has led to the end of other programs. Going forward, the company won’t be devoting resources to tinnitus and age-related hearing loss. But Reid says the research was still valuable, as it informed Decibel scientists about the biology of the inner ear and how to deliver therapies there. That knowledge is being applied to the remaining therapies in Decibel’s pipeline, and will help the company develop new regenerative therapies, he adds.

Decibel’s last financing was a $55 million Series C round of funding in 2018. Reid says the company has enough cash to last through most of 2020. He expects that later this year, Decibel will look to raise additional financing. He declined to specify how much, other than to say it would be enough to move one or more gene therapies into clinical testing and advance development of the company’s new regenerative medicine pipeline.

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