Geneticist Jim Wilson left UPenn behind, but not his dream of curing rare genetic diseases

Jim Wilson‘s pioneering gene therapy explorations have helped launch eight companies focused on translating his 40 years of research, mostly at the University of Pennsylvania, into treatments for rare diseases.

During that time, he learned a formula that appealed to investors: Advance the company’s science, make the company more valuable to bring in more investors, and then sell it to a big pharmaceutical company.

Then a couple years ago, Big Pharma lost interest in gene therapies for rare diseases. “When that avenue of liquidity evaporated, the whole thing shut down,” he said.

But Wilson, 69, wasn‘t ready to give up on his lifelong goal of developing gene therapies to cure patients with rare diseases.

“When we thought about our next step, what was critical to moving in this direction was not relying on the pharmaceutical industry to commercialize our products,” he said.

Wilson‘s answer was to leave Penn, his home for 33 years, to test a new business model for advancing gene therapy. He formed Gemma Biotherapeutics to partner with countries in Latin America and the Middle East, not just to raise money but also to ensure that treatments reach populations where the need is great.

He is now pitching what he calls a modular approach to getting treatments to patients: Bundle treatments for similar genetic diseases to reduce development costs, and focus on diseases for which there is a clear road map to reaching the marketplace.

That spinout of Philadelphia-based Gemma from Wilson‘s lab at Penn happened Oct. 1. His other business interests include Franklin Biolabs, a contract research organization that separately spun out of Wilson‘s lab at the same time and set up operations in King of Prussia.

Wilson left academia at a tough time for the gene therapy sector. Financially, investors are worried about limited applications for therapies with sticker prices that can climb into the millions, with ongoing safety questions.

And the science itself is evolving. Many labs are diversifying techniques beyond the viruses Wilson discovered and has used to deliver healthy genes into the human body.

He is looking to Brazil to start proving his concept. Wilson struck his first deal with Brazil‘s Ministry of Health, which agreed last year to spend up to $100 million to bring six treatments for rare central nervous system diseases to market over the next three to five years.

Wilson became interested in rare genetic diseases while in graduate school at the University of Michigan in the early 1980s. He studied a form of cerebral palsy in boys called Lesch Nyhan Syndrome.

The rare disease results in symptoms ranging from impaired kidney function to harm-inducing behaviors such as lip and finger biting. “They can’t talk, but they’re actually cognitively intact,“ Wilson said, noting that his five years studying these children led to his commitment to rare diseases.

He has persisted, despite significant setbacks. In 1999, an 18-year-old man named Jesse Gelsinger died after undergoing a gene therapy treatment that Wilson developed, setting the field back by years. For about a decade, “we couldn‘t do anything but just hunker down and try to move our science forward.”

As the field entered another major downturn in investment support — in addition to Wilson becoming a grandfather, the researcher considered whether it was time to let others carry on his dream of treating rare genetic diseases. “But I don‘t think there’s anyone but me that can really try to try to pull this off,” he said.

There’s another factor. The notion of his retirement didn‘t make his wife of more than 40 years happy. “COVID didn‘t go well, if you know what I mean,” he said.

Still, Wilson‘s departure from Penn came amid a painful slowdown in venture capital investment in biotech. Gene therapy has been hit particularly hard. The amount of venture capital invested in gene therapy globally fell to $1.4 billion last year from a peak of $8.2 billion in 2021, according to Reuters.

The gene therapy section “is in a dark place right now, and it’s a shame, because the science, while not fully there, is on the cusp of some greatness,” said John F. Crowley, CEO of the Biotechnology Innovation Organization, an advocacy group in Washington and a Bucks County resident.

There were signs after last fall’s presidential election that private equity and biotech investing would recover from the slump that started in 2022, but now political and regulatory turmoil under President Donald Trump has made executives skittish about deal making.

Pension funds, endowments, and others who poured money into funds that backed biotech start-ups are “hankering for exits,” said Dean Miller, CEO of the Philadelphia Alliance for Capital and Technologies, a group that advocates for start-ups in the region.

Despite the difficult environment, Wilson announced late last year that he had raised $34 million in seed capital from four investment firms. Now he’s out trying to raise enough to give Gemma three years of runway. He declined to say what his target is.

Companies focused on rare diseases have had an especially hard time finding financial success with gene therapies because the costs are high and the markets are small.

Steven Altschuler, a biotech investor who helped found Philadelphia’s Spark Therapeutics a decade ago when he was CEO of Children‘s Hospital of Philadelphia, said he would not discount Wilson‘s ability to raise money.

“For high profile people, there’s still opportunity, but it’s much less than it used to be,” Altschuler said.

Wilson has a two-pronged approach to addressing the business challenges threatening the medical applications of his research.

Gemma’s plan is to partner with middle-income countries that have national healthcare systems to share in the cost of commercializing treatments. The company already has a deal with Brazil, and is seeking a partner in the Middle East, where Wilson said genetic disease is more prevalent than in other regions of the world.

Gemma is also working on a bundle of treatments for similar genetic diseases to reduce development costs, with the goal of ultimately reaching $500 million in annual revenue.

“If you just have one really rare disease as a company, it’s not cost effective to develop a worldwide commercial enterprise to commercialize that,” Wilson said.

Another key to Gemma’s strategy is targeting diseases that have no other treatment. Specifically, he looks for diseases and treatments with straightforward ways to verify that the treatment worked, even with a small number of patients in a trial.

An advantage to working with national health systems is that they provide insurance coverage for life. That means the high cost of genetic cures makes sense financially in the long term because the insurer that pays for the treatment saves money over the patient’s entire life.

By contrast, in countries like the United States, the economics are more complicated, experts said.

“The reimbursement side of it is not really set up to absorb those significant upfront costs,” Miller said of the U.S. system, because people frequently change insurance companies. That makes it hard for an insurer to pay a multimillion dollar tab for a gene therapy cure, only to see the patient leave for a different insurer.

Wilson struck his first deal with a national health plan in Brazil, where he has experience with clinical trials.

Gemma is on track to treat its first patients in Brazil this year, Wilson said.

Brazil’s health ministry will cover the cost of clinical trials involving an estimated 10 to 30 patients. That means Gemma doesn‘t have to spend investor money on this developmental stage, Wilson said. He estimated that trials are expected to cost from $300,000 to $1 million per participant.

Wilson built Gemma keeping in mind what he called a series of gates that all new treatments have to get though to succeed in the marketplace.

He breaks down the steps as: developing the right technology with the right dose, securing regulatory approval for safety, negotiating adequate pricing from insurers, and gaining acceptance by doctors. In other words, doctors have to prescribe the medication.

Having the right dose is particularly important in gene therapies that his approaches deliver into the human body using modified viruses, called vectors. “It’s a convenient way to deliver the treatment, but it has its challenges,” Wilson said.

To ensure the vectors carrying the new gene reach their target, sometimes the doses have to be so high that they become toxic and potentially deadly. Plus, the cost of producing that much of the vector can be exorbitant, Wilson said.

Gemma is trying to avoid those risks by targeting diseases of the central nervous system, with the vector injected into the cerebral spinal fluid. “You use less of it. It’s localized, more efficient, and you’ll have far less toxicities,” Wilson said

He also aims to avoid the fate of some gene therapies, like those approved in recent years for the blood disorder hemophilia B, that haven‘t met sales expectations because there are cheaper, existing treatments that work well. So doctors aren‘t prescribing them.

Gemma’s rare disease targets have no alternative treatments. That means Wilson expects to see patients and their families line up.

Wilson is targeting diseases that don‘t require as burdensome a treatment process as is the case for some gene therapies, which require families to move to be near an advanced care center for two months.

“To get our product, you have to be on-site about three to four days,” he said.