Passage Bio completed a $115.5 million series A financing to develop a portfolio of five preclinical therapeutic candidates to treat rare, genetic, central nervous system diseases.

OrbiMed Advisors led the round, which included investment from Frazier Healthcare Partners, Versant Ventures, New Leaf Venture Partners, Vivo Capital, and Lilly Asia Ventures.

The biotech was founded by gene therapy pioneer James Wilson, professor and director of University of Pennsylvania’s Gene Therapy Program; Stephen Squinto, interim CEO, venture partner at OrbiMed, and co-founder of Alexion Pharmaceuticals; and Tachi Yamada, Passage Bio’s chairman and venture partner at Frazier Healthcare. Yamada previously served as chief medical officer and chief scientific officer at Takeda Pharmaceuticals.

Based in Philadelphia, Pennsylvania, Passage Bio will work under a research, collaboration, and license agreement with the University of Pennsylvania and its Gene Therapy Program together with the Penn Orphan Disease Center. The Gene Therapy Program will conduct preclinical work, and Passage Bio is responsible for clinical development, regulatory, manufacturing, and commercialization of all product candidates.

The Orphan Disease Center is responsible for natural history studies, key opinion leader engagement, and patient advocacy outreach. Passage Bio also has an option to fund the preclinical development of up to seven additional rare monogenic CNS indication programs at the Gene Therapy Program and license new intellectual property arising from these programs from Penn.

“Passage Bio’s development portfolio presents an unparalleled opportunity to transform the lives of patients with rare monogenic CNS diseases,” said Squinto. “We look forward to continuing progress in this exciting field of therapeutics and advancing our lead programs in GM1 gangliosidosis and frontotemporal dementia into the clinic in early 2020.”

Wilson is a pioneer in the development of adeno-associated virus vectors (AAV) for delivery of gene therapies with more than 550 papers and 110 patents under his belt. He was one of the first proponents of gene therapy for rare monogenic disorders. Gene therapy was hailed as a medical breakthrough in the early 1990s for its potential to transform the lives of patients with genetic diseases. Research in the area, though, came to a standstill after the death of clinical trial participant Jesse Gelsinger in 1999 due to an experimental therapy administered by Wilson’s team.


Wilson was banned from research in the area for five years. As Wilson investigated why Gelsinger had died, he consulted with his early mentor Yamada, then at Takeda. Yamada encouraged him to solve Gelsinger’s death, stay with gene therapy, and develop a better way to deliver it without causing a fatal immune response. That led to Wilson’s research with AAVs and his teams’ development of AAVs with safer delivery profiles.

“Our team at Penn is extremely experienced and has been on the cutting edge of AAV research for over 20 years,” said Wilson. “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 Bio will initially focus on GM1 and frontotemporal dementia, for which there are currently no disease modifying therapies. GM1 is a lysosomal storage disease marked by the absence of lysosomal enzyme β-galactosidase (GLB1), which is required for the degradation of GM1 ganglioside and keratan sulfate. Without GLB1, a lipid called GM-1 accumulates in cells, especially in the brain, causing progressive damage. The infantile type of GM1 is the most common and severe form of the disease, typically with gait abnormalities by four months of age and developmental regression by six months. Most GM1 patients die by two years of age.

Frontotemporal dementia (FTD) typically presents in older people between 60 and 70 years of age with progressive impairment of executive function, language, and social interaction. These symptoms are associated with a characteristic pattern of neurodegeneration affecting the frontal and temporal cortices. In 5 to 10 percent of FTD patients, pathogenic loss-of-function mutations can be identified in the gene encoding progranulin, a ubiquitous lysosomal protein. Patients universally exhibit a progressive course, with an average survival of eight years from symptom onset.

Photo: James Wilson, co-founder of Passage Bio