Going viral: gene therapy spreads far and wide

Gene and cell therapies promise to dramatically change how dozens of devastating inherited diseases are treated. These products are also transforming the way paediatric academic medical centres move research discoveries from the laboratory to commercial approval, says Matt McFarland, vice president of commercialization and industry relations at Nationwide Children’s Hospital. “People don’t think of a nonprofit like Nationwide Children’s Hospital as a hotbed of biotechnology commercialization, but they should.”

Technology transfer officers such as McFarland — as well as the physicians and scientists who conduct these pioneering investigations — now co-develop new genetic medicines with industry partners, he adds. “This is a paradigm shift away from the old model of academic institutions focusing solely on basic science, such as identifying potential biological targets for pharmaceutical companies to design new drugs around.”

This growing trend highlights the ever evolving, and increasingly entrepreneurial, role that children’s hospitals play in the development of genetic medicines, says paediatrician Dennis Durbin, president of the hospital’s Abigail Wexner Research Institute (AWRI). “We’re now involved in everything from the initial discovery to early preclinical development, first-in-human clinical trials, clinical manufacturing, co-investing in the initial start-up, and ultimately licensing the technology to an industry partner to take it across the finish line.”

AWRI has essentially built a biotech company inside the walls of a 131-year-old hospital, he adds. “Of the first eight FDA-approved gene therapies, two — Elevidys for Duchenne muscular dystrophy (DMD) and Zolgensma for spinal muscular atrophy (SMA) — were invented and developed here.” Ranked for more than a decade among the top ten NIH-funded paediatric research facilities, AWRI has a rich pipeline of gene therapies for other life-threatening neuromuscular diseases, including amyotrophic lateral sclerosis (ALS) and limb girdle muscular dystrophy. To build on these successes, Nationwide Children’s recently announced plans for a five-year $3.3 billion expansion of its research and treatment programmes — its most ambitious ever.

A bold vision

AWRI’s Centre for Gene Therapy was founded in 2002 — a time when gene therapy research had come to an almost complete halt, after a series of significant setbacks, and investment dried up. Nationwide Children’s however invested heavily in infrastructure aimed to help its physician-scientists overcome those setbacks. “We didn’t want to give up and see more children die from inherited diseases when we thought we were close to finding something to help them,” says paediatric neurologist Jerry Mendell, one of the centre’s principal investigators. “Parents whose babies had SMA — the leading genetic cause of infant mortality — were being told by their physicians to take their infants and love them while they still could; those whose children had DMD were being advised to take them on lots of family trips while they were young, because they’d be in a wheelchair by age 11 or 12.”

Instead of relying on an outside lab, the institute was one of the first paediatric academic medical centres to build its own Good Manufacturing Practice (GMP) facility, enabling the development of innovative viral vectors and gene therapy products for clinical and preclinical research. The hospital also initiated other core capabilities, including high-end computing, genomic medicine, and clinical trial infrastructure.

Once the centre’s investigators were ready to launch first-in-human studies of novel therapeutic genes, Nationwide Children’s in-house regulatory affairs office helped guide them through the FDA’s complex regulations governing the conduct of trials of new drugs and devices in human subjects, particularly those involving small children, adds Durbin. “Because genetic diseases like SMA and DMD start to affect babies in utero, we wanted to evaluate gene therapies for these patients at the youngest possible age, when the likelihood of halting or reversing the disease was greatest.”

A magnet for investors

Forward thinking and an entrepreneurial culture have been key to the success of the hospital’s research enterprise, says McFarland. “We make substantial investments to derisk our world-class researchers’ discoveries, thereby advancing them to a point where they’re extremely attractive to venture capitalists, entrepreneurs and pharmaceutical companies.”

This strategy has paid off: over the past decade the hospital’s annual deal flow has soared by 900%. In 2022, McFarland says his team evaluated 73 new invention disclosures, filed more than 160 patent applications, and finalized 18 licensing deals, with 87 others in progress at year’s end. Among Ohio organizations that license their technology, Nationwide Children’s has consistently ranked as a top earner for gross revenue from these tech-transfer deals. Currently, over 70% of its patent portfolio is licensed to industry partners and 28 of these technologies are now in clinical trials, he reports.

In addition, Nationwide Children’s has spawned about a dozen gene therapy start-ups; some of which have been sold to pharmaceutical giants. One notable example, AxeXis, was acquired by Novartis for $8.7 billion in 2018. Renamed Novartis Gene Therapies, it focuses on developing treatments for neuromuscular diseases, including SMA — licensed from Nationwide Children’s. In 2020, the hospital spun off its GMP facility to launch Andelyn Biosciences, of which it owns a majority stake. Andelyn is a commercial-scale operation in a new $200 million manufacturing headquarters that opened in June 2023.

Fuelling Central Ohio’s biotech boom

The hospital’s decades-long investment in life-changing therapies is a driving force behind an era of unprecedented economic growth in Columbus, Ohio. The city is now among the nation’s fastest-growing biotechnology hubs, says Eddie Pauline, president and CEO of Ohio Life Sciences, a trade group for biotech, pharmaceutical, gene therapy and academic organizations. “Nationwide Children’s and its spinoffs have built so many state-of-the-art research facilities that it’s starting to create a new city skyline.”

Recently ranked by Forbes as the top rising city for start-ups, Columbus is also attracting established biotechs — even from states with their own renowned academic medical centres. For example, Sarepta Therapeutics, the Cambridge, Massachusetts biotech that licensed Nationwide Children’s gene therapy for DMD, as well its therapies for six other subtypes of muscular dystrophy, opened its Genetic Therapies of Excellence research facility in Columbus in 2021.

Through its prowess in generating spinoffs, licensing deals and industry partnerships, the hospital has created a cycle of ongoing growth, in which revenues from these ventures are reinvested in the organization and its pipeline — and its resources attract top research talent to invent the next generation of gene therapy breakthroughs.

“Thanks to bold thinking by Nationwide Children’s leadership, and a willingness to take risks for the right reasons,” says Pauline, “the ‘incurable’ is now closer than ever before to being cured.”