Longtime biopharmaceutical executive Tachi Yamada helped keep the work of gene therapy pioneer James Wilson alive 20 years ago when Wilson was mired in controversy and the emerging field was in its darkest days.
Now that gene therapy has come of age, in part because of Wilson’s work, the two are teaming up again. They’ve co-founded a startup, Passage Bio, which aims to use the technology to treat a slew of rare brain diseases.
Passage, which has a broad alliance with Wilson’s gene therapy center at the University of Pennsylvania and is based in Philadelphia, has raised a $115.5 million Series A round led by OrbiMed Advisors. The company’s CEO is former Alexion Pharmaceuticals (NASDAQ: ALXN) co-founder Stephen Squinto, who teamed with Wilson and Yamada—now a venture partner at Frazier Healthcare Partners—to form the company. Wilson is the firm’s chief scientific advisor, while Yamada is Passage’s chairman.
Passage will use the cash to advance five gene therapies discovered at UPenn. It also has an option to fund and license another seven. The most advanced of that group are two gene therapies: one for GM1 gangliosidosis, a disease that can kill infants by the age of two, and the other for a subset of patients with frontotemporal dementia. These two therapies should begin human testing early next year, the company said in a statement. Under their collaboration, UPenn conducts the preclinical work, then hands the gene therapies off to Passage for clinical testing and eventually commercialization, if all goes well.
The financing comes at a time of great momentum for gene therapy, which has taken decades to begin to fulfill its promise. The idea is to use a modified virus or some other “vector” to deliver healthy genes into a cell to replace faulty or missing ones. In theory, this could attack the root cause of a patient’s disease and provide a long-lasting, if not permanent treatment through a single procedure. But despite the billions of dollars poured into gene therapy research and startups in the ‘90s, it took years of ups and downs for the first gene therapy to win FDA approval for commercial use—a treatment, Luxturna, for a genetic form of vision loss.
Gene therapy’s long roller coaster ride was due to safety problems and difficulties with delivering the new genes. And Wilson was an important figure in both gene therapy’s fall and subsequent rise.
Wilson co-led the infamous clinical trial that led to the death of teenager Jesse Gelsinger in 1999, which chilled investment in gene therapy for years. But his work continued thanks to Yamada, an old mentor and at that time the chief scientific officer of SmithKline-Beecham (now GlaxoSmithKline). (Yamada later became a top executive at Takeda.)
As Wilson told Xconomy in 2015, he turned to Yamada for advice during the tough times when he was barred for five years from working on human clinical trials. Yamada encouraged Wilson to continue his research, and through GSK, helped fund it. “He said ‘I believe in you. I think you can do it. So how much money do you need?’” Wilson said in 2015. “I said ‘What do you mean?’ He said: [SmithKline-Beecham] would love to fund you in this endeavor.’”
That turned out to be a critical moment for gene therapy. Wilson went on to become a key figure in advancing what’s now the most commonly used gene therapy delivery tool, the adeno-associated virus, or AAV. A company Wilson co-founded, RegenXBio (NASDAQ: RGNX), licenses AAV vectors to several companies. And AAV vectors are used to deliver many of the most advanced gene therapy products: Luxturna, experimental gene therapies for hemophilia and spinal muscular atrophy that are nearing FDA approvals, others in human trials for Duchenne muscular dystrophy, Parkinson’s disease, and more. The technology has come so far that the FDA has recently announced long-term plans to accommodate the surge in expected approval filings for gene therapies.
“Our team at Penn is extremely experienced and has been on the cutting edge of AAV research for over 20 years,” said Wilson in a prepared statement. “We are confident in this team’s ability to move new treatments for rare CNS monogenic diseases through clinical development in an effort to one day provide new treatment options for patients with chronic unmet needs with high mortality.”
Passage, meanwhile, is the second company in just the past week to raise money to develop gene therapies for neurological diseases. Neurogene, of New York, announced a $68 million Series A on Tuesday.
Passage and Neurogene join a small group of companies specifically formed to target the brain with gene therapy. Others include Voyager Therapeutics (NASDAQ: VYGR) and Prevail Therapeutics, which are going after Parkinson’s and other neurodegenerative diseases.
In addition to OrbiMed and Frazier, Versant Ventures, New Leaf Venture Partners, Vivo Capital, and Lilly Asia Ventures also participated in Passage’s financing.