Gene therapy start-ups are off to a roaring start in 2019. In January, Apic Bio launched with $40 million to treat ALS and liver diseases. Earlier this week, Neurogene launched with $68.5 million to tackle several neurological and lysosomal storage disorder diseases.
Now, University of Pennsylvania professor James Wilson, one of the biggest names in gene therapy, has a startup of his own called Passage Bio. It has raised $115.5 million in series A financing to develop gene therapies for rare genetic diseases of the central nervous system.
The launches follow last year’s approval in the US of the first viral-based gene therapy: Spark Therapeutics’ Luxturna, which treats a rare form of inherited blindness. This year, Novartis expects, the US Food and Drug Administration will approve the second gene therapy, Zolgensma: Novartis’s treatment for a deadly disease called spinal muscular atrophy. The FDA recently announced it will hire dozens of new clinical reviewers to prepare for the hundreds of gene-therapy applications it expects to receive in the next couple of years.
The current explosion wasn’t inevitable. Gene therapy was in vogue in the 1990s, before the first draft of the human genome was even published, but the field came to a halt in 1999 when news broke that an 18-year-old boy died in a gene therapy clinical trial. Wilson, who led the trial, thought about leaving the field, but he was encouraged to carry on by a mentor and former colleague from the University of Michigan, Tachi Yamada.
Soon after, Wilson’s research on adeno-associated viruses (AAVs) helped slowly reinvigorate the field. Researchers need viruses as shipping packages to get the DNA of a gene therapy into the body and into the right cells. AAVs turned out to be safer and more effective than the older viruses Wilson had used. In 2009, Wilson helped found the AAV-based gene therapy company REGENXBIO. It now licenses AAVs to 11 other companies, including Novartis, which uses a variant called AAV9 as the basis of Zolgensma.
Passage Bio was born out of Wilson’s desire to start a venture that he could be intimately involved with, explains Stephen Squinto, a partner at the venture capital firm OrbiMed Advisors, who is currently serving as Passage’s CEO. Squinto, who cofounded the rare-disease company Alexion Pharmaceuticals, spotted a unique opportunity when he first visited Wilson’s lab at Penn. “He runs his gene-therapy center like you’d run a very efficient company,” Squinto says.
That observation, he says, led to a unique arrangement for Passage: “Why not use the world’s most proficient AAV lab to do your preclinical work?” Wilson, Squinto, and Yamada—who is now a partner at Frazier Healthcare Partners—decided to found Passage under the premise that the company would pay Wilson’s lab to create AAVs and run experiments in monkeys. Passage will take over once it’s time to petition the FDA for permission to run experiments in humans.
“It will be a drug-development organization without a research and discovery group, because we are leveraging the expertise of Penn for that purpose,” Squinto says.
Although the company is new, the preclinical research is quite mature, Squinto says. Passage is focusing on five rare diseases that Wilson’s lab has already been studying. Squinto expects to begin clinical studies for three of these programs in 2020. The two most advanced ones are for a disease that affects and often kills infants called GM1 gangliosidosis and for a disease that affects adults called frontotemporal dementia.
Thus far, most companies use specific varieties of AAVs to get gene therapies into different parts of the body. For instance, some firms, including Spark for Luxturna, use a variant called AAV2 to get genes into the eye. Several companies are using AAV8 in experimental therapies that deliver genes to the liver. And AAV9 is widely used in clinical trials to deliver genes to the brain and spinal cord.
“We’ve kind of thrown a lot of that out at Passage,” Squinto says, in favor of a different approach to AAVs. He won’t be specific but says it may involve engineering the viruses to suit them for a particular disease or using existing AAVs in new ways. “It is probably going to surprise some people,” Squinto says, “because some of it goes against the dogma in the field.”