[Updated, 6/19/18, 4:20 p.m. See below.] Hearing loss affects millions of Americans, but so far, drug companies have not yet brought treatments to the market. Decibel Therapeutics aims to pioneer the discovery and development of therapies addressing multiple forms of hearing loss. The startup has quietly built a pipeline of experimental drugs, and as those compounds advance toward human testing, it now has $55 million in fresh capital to back clinical studies.
The new capital, from a Series C round of funding, will support multiple drugs for hearing loss. By this time next year, Boston-based Decibel should have two compounds in clinical testing, says CEO Steven Holtzman. A third treatment, a gene therapy, is expected to enter clinical trials within two years. Holtzman says pursuing multiple drug candidates simultaneously is a way of building value for the company while also diversifying risk. He points to the approach of Genentech in the 1980s and its work on recombinant DNA, as well as Millennium Pharmaceuticals, which built a diverse cancer drug pipeline in the 1990s.
“We are also building, aggressively, and at the same time, not wildly spending,” Holtzman says.
The most advanced Decibel compounds were developed to protect against hearing loss caused by other drugs. Hearing loss is a side effect of as many as 600 drugs, including painkillers such as aspirin and non-steroidal anti-inflammatory drugs, Holtzman says. It’s also a side effect of cisplatin, a chemotherapy that is a first-line treatment for a number of cancers.
Decibel has two compounds for hearing protection, one an oral formulation and a second that is administered locally to the ear. One of the drugs was developed to prevent hearing loss in cancer patients receiving cisplatin treatment. Those patients lose hearing because chemotherapy kills cells involved in the process of hearing as well as cancer cells, Holtzman says. In preclinical studies, the drug protected hearing in mice. Decibel administered the drug to one ear while leaving the other ear untreated—making the mouse’s own untreated ear the control in the experiment. In the tests, “the unprotected ear has severe hearing loss and the drugged ear is protected 100 percent of the time,” Holtzman says. [Paragraph updated to clarify hearing protection drug programs.]
The company is also developing drugs to restore hearing. In 80 percent of the cases where a newborn has hearing loss, the cause is genetic, Holtzman says. Decibel is working on gene therapies to correct genetic defects. Holtzman says Decibel is pursuing a number of potential gene therapies, and the company expects to select candidates for clinical testing in the first half of next year. Clinical trials could begin by early 2020.
Decibel’s research on therapies to repair hearing are part of a wide-ranging partnership with Tarrytown, NY-based Regeneron Pharmaceuticals (NASDAQ: REGN). Holtzman says the hearing loss that comes with age is not a loss of volume, it’s the diminished ability to distinguish one sound from another, such as voices in restaurants and other noisy environments. Decibel scientists have found that this type of hearing loss is the result of damage to the sensory nerves of the ear, he adds.
Decibel and Regeneron are working together to develop drugs that treat this nerve damage. The partnership, which began last fall, covers multiple drug candidates, including gene therapies, and includes conditions such as tinnitus, the perception of ringing or other noise in one or both ears. The partners are sharing equally in development costs, but Decibel retains all of the rights to the compounds, Holtzman says. Regeneron, which took a “significant equity position” in Decibel when the partnership began, will be eligible to receive royalties from any commercialized therapies that emerge from the alliance. [Paragraph updated to clarify details about the Regeneron partnership.]
A handful of companies large and small are pursuing therapies to treat hearing loss. The startup Frequency Therapeutics, an MIT spinout, is trying to treat hearing loss by activating dormant “progenitor” cells that can morph into other types of cells. The idea is to coax these cells into creating new inner ear cells that are key to hearing. Meanwhile, Novartis (NYSE: NVS) is testing a gene therapy for hearing loss in a Phase 1/2 clinical trial.
Decibel launched in 2015, backed by $52 million in financing from Third Rock Ventures and SR One, the investment arm of GlaxoSmithKline (NYSE: GSK). The company’s earlier investors, including Third Rock Ventures, GV, SR One, and Regeneron, participated in the Series C funding. Also joining the latest financing were new investors Foresite Capital, Bessemer Venture Partners, Schroder Adveq, S-Cubed, Longevity, and other institutional investors whose names were not disclosed. Along with the financing, Decibel announced that Anthony Philippakis, venture partner at GV, has joined the company’s board of directors. George Scangos, CEO of Vir Biotechnology, was named chair of the board.
Image by Depositphotos user Pixelchaos