It was a milestone to celebrate: Earlier this year, designations from FDA and European Union regulators moved researchers at the Boston-based startup Akouos, Inc., a step closer to producing the first-ever therapy for gene-mediated hearing loss. The product could change the lives of an estimated 20,000 adults and children in the United States and Europe who are living with profound hearing impairment caused by a specific type of gene mutation.

“There are more than 150 genes linked to hearing loss,” explains cofounder Manny Simons (MBA 2012), who says the company’s research builds on decades of scientific inquiry in gene-based hearing loss and inner-ear drug delivery: “In some infants with profound hearing impairment, there’s a mutation in one of those genes that results in loss of a protein that inner-ear cells need to convert sound waves into electrical activity the brain can interpret as sound. Getting a healthy copy of the critical gene to the appropriate cells is a solution, but precision inner-ear drug delivery has been a historical stumbling block. An early breakthrough for us was figuring out a way to pair gene therapy with a one-time surgical administration to deliver genes to the inner ear with unprecedented efficiency.”

The five-year-old company will likely apply for clinical testing permission for its lead therapy in the first half of 2022—a key hurdle in the notoriously lengthy process of advancing novel medicines from seed to market. CEO Simons, who has a doctorate in biomedical engineering and readily admits he still identifies as a scientist, is equally excited about the big-picture impact of receiving orphan drug and rare pediatric disease designations. “Disabling hearing loss affects more than 400 million people across the globe,” he says. “It has a variety of known causes, but this is the first time a genetically driven form of hearing loss has received rare disease recognition. We think the designation will broaden medical research in this field and ultimately lead to a range of new targeted therapies.”

Curiosity and imagination are common threads in Simons’s career. He grew up in a musical family, studied piano and trumpet, and chose a joint music and neuroscience major at Harvard College to investigate the physiologic basis of music therapy. “That turned out to be a space for a lot of cross-disciplinary ideas,” he observes. “I learned not to divide topics into their relevance to another topic. You just don’t know where ideas will lead you.”

Ideas led Simons to doctoral studies in the lab of MIT biotech pioneer Robert Langer. “New knowledge comes from unexpected places, and Bob’s lab was eye-opening in that respect,” Simons recalls. “I met a ton of brilliant people with diverse expertise and ambitions—science, engineering, academic research, startups. That’s where I got interested in studying at HBS.”

Simons saw entrepreneurship as “the best path to translate breakthrough research into something that can help people.” He launched Akouos (Greek, for “to listen”) with a realistic attitude about risk and a flexible definition of success. After leaving his senior post at another Boston-area biotech firm, an HBS Blavatnik Fellowship provided a year of funding and transitional time to spend in the lab and assemble a team of scientists, clinicians, and managers. “When you’re attempting something no one has ever done before, humility is a key quality,” he cautions. “You can’t be fixated on one model of success. Technology and financing landscapes change constantly, and you have to adapt.”

Biotech ventures have what Simons refers to as “many potential failure modes,” and raising capital can be tough. Akouos netted $224 million in its successful IPO in 2020, but looking back, he credits venture capital firms 5am Ventures and New Enterprise Associates for critical early support. “There were a lot of things still in the process of coming together,” he says, “and I had never been a CEO before. They took a risk on me and the technology.”

Five years later, Simons is mostly focused on organizational development, board meetings, strategy sessions, stakeholder outreach, and other CEO duties. In addition to its lead product, the company’s research pipeline now includes potential therapies for a variety of disabling inner-ear disorders.

“I know how fortunate I am to have found meaningful work that I enjoy,” says Simons. “Hearing loss is one of the greatest unmet challenges in medicine. It’s an amazing privilege to be involved in this field at a time when advances by Akouos and others could improve the practice of medicine in ways we are just beginning to imagine.”

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