A year ago Passage Bio launched with $115.5 million and plans to advance a handful of gene therapies discovered at the University of Pennsylvania.
Now the Philadelphia-based biotech is preparing to join the public markets and raise millions more to move its three lead programs into the clinic.
Passage, which has three preclinical programs and that many again in the discovery or candidate selection stage, set a $125 million target for its IPO, and said it plans to list on the Nasdaq under the stock symbol “PASG.”
Gene therapies use functioning genes, delivered within a modified virus or other “vector,” to replace ones that are faulty or missing. The first gene therapy that received FDA approval for commercial use, Luxturna, for a genetic form of vision loss, was OK’d just over two years ago. (Luxterna developer Spark Therapeutics (NASDAQ: ONCE), also based in Philadelphia. was acquired by Roche for $4.3 billion in a deal that concluded in December.)
Now many companies are racing to bring such treatments, which are intended to provide a long-lasting, if not permanent effect, to bear on a wide range of diseases. Passage aims to tackle disorders of the central nervous system that involve a single gene. Under the biotech’s agreement with Penn, the university handles discovery and preclinical development. Passage is poised to start its first clinical trial this year and two more next year.
Passage’s PBGM01 is intended for patients with infantile GM1 gangliosidosis, the most severe type of the condition, which causes progressive destruction of neurons in the brain and spinal cord. Caused by mutations in the GLB1 gene, babies born with infantile GM1 typically don’t live past age 2. The company estimates infantile GM1 affects 1.4 in 100,000 live births.
The Passage therapy is designed to deliver a functional GLB1 gene to the brain and peripheral tissues. Passage describes the delivery vehicle, or “vector,” as a proprietary, “next-generation” AAVhu68 capsid.
The company aims to ask the FDA for permission to start human testing in the first half of 2020 followed by the start of a Phase 1/2 trial in the second half of the year.
There are some other companies that are also developing GM1 gene therapies. New York-based Axovant Gene Therapies (NASDAQ: AXGT) is already in the clinic with a gene therapy for juvenile GM1, which progresses more slowly than the infantile type, but still decreases life expectancy. Axovant dosed its first patient in May 2019. Meanwhile, France’s Lysogene, is preparing to ask for FDA permission to proceed with human testing of its gene therapy for GM1.
Another Passage program, PBFT02, is being developed for patients with frontotemporal dementia (FTD), a form of dementia that is caused by a deficiency of a protein called progranulin. That therapy uses an AAV1 capsid to deliver to the brain a gene that encodes that protein. The company says about 3,000 to 6,000 people in the US have this form of FTD.
Passage plans to ask the FDA for the OK to move into the clinic in the second half of this year and start a Phase 1/2 trial in the first half of 2021. But the company also faces potential competition in this disorder.
Other biotechs developing treatments for FTD with GRN mutations include Alector (NASDAQ: ALEC) in South San Francisco, which is testing a monoclonal antibody intended to increase levels of progranulin in a Phase 2 clinical trial, and New York-based Prevail Therapeutics, which is poised to advance a gene therapy for the condition into the clinic.
The third preclinical Passage program, PBKR03, is in development for the treatment of infantile Krabbe disease, an inherited condition caused by mutations in the GALC gene that affects the nervous system, causing a range of signs and symptoms such as irritability, slowed development, progressive muscle weakness, hearing loss, and vision loss. The company says it is believed to affect 2.6 in 100,000 births.
PBKR03 uses Passage’s proprietary viral vector to deliver a functional GALC gene to the brain and peripheral tissues. Passage plans to ask the FDA for authorization to move into human testing in the second half of this year and to start a Phase 1/2 trial in the first half of 2021.
Passage has three discovery-stage programs for forms of metachromatic leukodystrophy, amyotrophic lateral sclerosis, and Charcot-Marie-Tooth disease associated with specific mutations. The biotech has the option to license up to six more programs from Penn through 2022.
As of Dec. 31, the company said it has raised $225.5 million, and that it had cash and equivalents totaling $158.9 million. Its biggest outside shareholders are OrbiMed, which owns 19.6 percent of Passage’s shares; Versant Ventures, which owns 14.8 percent; and Frazier Life Sciences, which owns 13.9 percent, according to its prospectus.
Last week it appointed Bruce Goldsmith, a venture partner at Deerfield Management, as its new CEO. James Wilson, who heads the gene therapy center at Penn, is Passage’s chief scientific advisor.