Discovery NETWORK: AskBio and a few dozen other firms are making North Carolina a pace-setter in highly targeted drug development.

• Author: MacMillan, Mike

There's a story that Jude Samulski, perhaps the worlds preeminent gene-therapy research scientist, likes to tell.

It's about a fellow with a degenerative eye disease who is asked to navigate an obstacle course. He wanders, bumping into things and getting disoriented. It takes 76 seconds to finish the course. Six months later and following gene-therapy treatment, he's back on the course. This time, there's no disorientation. It takes 14 seconds.

It's an apt metaphor for the industry itself--years of groping in the dark, of following promising leads that don't pan out, and then, finally, emerging into the light. There were early missteps as researchers struggled to understand the technology. There was the highly publicized 1999 death of a young patient participating in a trial for a rare metabolic disorder. There was the ebb and flow of capital directed to the industry.

Still, researchers continued to plug away in their labs. One was Samulski, who came to UNC Chapel Hill in 1993 from the University of Pittsburgh, lured in part by a $430,000 faculty recruitment grant from the N.C. Biotechnology Center. He was a true believer.

"We knew from the beginning what this technology (gene therapy) could do," he says. "We knew if we could make it work, we could change the world."

Today, there are seven cell and gene therapies approved in the U.S. with dozens more expected in the coming years, according to the Milken Institute. There are about 1,000 in various stages of development with 50 to 75 new therapies expected to be approved in the U.S. by 2030.

These treatments are sometimes referred to as a "third wave," following small molecule therapeutics and biologies. The promise is enormous. "Molecular medicine will change how we treat disease," says Samulski. "We're genetic beings. You fix (a disease) one time (with gene therapy) and it's over."

Eye-popping price

This progress has not gone unnoticed, leading to massive investment in companies involved in the research. In 2018, Novartis bought the gene-therapy company AveXis for $8.7 billion. Its primary therapy, Zolgensma, is used to treat spinal muscular atrophy, the leading genetic cause of infant death, and it produces more than $1 billion in annual revenue. Last year, Roche acquired Spark

Therapeutics, a developer of gene-therapy treatments for hemophilia and blindness, among other diseases, for $4.8 billion.

North Carolina is in this game in a big way: in 2020, AskBio, a Chapel Hill-based company co-founded by Samulski and Sheila Mikhail in 2001, was acquired by Germany's Bayer for $2 billion up front and $2 billion in incentive payments. At the time, AskBio had about 294 employees and nominal revenues relative to the purchase price. Its principal investors were the TPG Capital and Vida Ventures private-equity firms.

Seeing investors drop eye-popping sums on developmental stage companies with little or no revenue is not uncommon in the biotech industry, but AskBio was different. It had already spun out several companies, most significantly Bamboo Therapeutics, a Chapel Hill-based developer of gene therapies for rare neuromuscular diseases. In 2016, Pfizer paid about $200 million up front for Bamboo, with potential milestone payments of as...