Avrobio has had encouraging early results testing its experimental gene therapy to treat Fabry disease, an inherited enzyme deficiency that leads to a dangerous fatty buildup in the body. As the biotech startup gears up for more tests, it now has $60 million more in financing to support those studies and the rest of its gene therapy pipeline.
Cormorant Asset Management and Surveyor Capital co-led the Series B investment in the Cambridge, MA-based company. With the cash, Avrobio says it will start a Phase 2 study testing its Fabry disease gene therapy, AVR-RD-01, later this year.
Fabry disease is a genetic disorder that leads to the deficiency of a key enzyme needed to break down a fatty substance called globotriaosylcera-mide. Without the enzyme, this fatty substance builds up throughout the body, affecting tissues and organs. Such metabolic diseases are called lysosomal storage disorders. According to the Fabry Support & Information Group, Fabry disease affects one in every 40,000 people.
Avrobio has developed a treatment it believes could offer Fabry patients convenience and cost savings compared to the standard of care. For treatment of lysosomal storage disorders, that standard is enzyme replacement therapy. Pioneered by companies such as Genzyme and Shire (NASDAQ: SHPG), these treatments require patients to receive twice weekly infusions that administer the deficient enzyme. Geoff MacKay, Avrobio’s co-founder and CEO, says his company’s treatment could deliver the correct enzyme to all of a patient’s organs all the time, halting the progression of the disease.
Gene therapies use modified versions of viruses to introduce genetic material into a cell. Avrobio’s therapies use what’s called lentiviral technology. The company harvests stem cells from a patient, then uses a virus from the lentivirus family—potentially deadly viruses that are genetically modified to be safe—to introduce a functioning version of the enzyme-producing gene into those cells. After being grown in culture, those stem cells are then infused back into the patient. Those cells go on to produce more cells that have the gene needed for production of the enzyme that a patient needs.
The ex vivo—outside of the body—approach that Avrobio uses is different than the one taken by Spark Therapeutics (NASDAQ: ONCE) and some other gene therapy developers. Spark, which late last year received FDA approval for its gene therapy to treat a rare, inherited form of blindness, uses an adeno-associated virus (AAV) to introduce the therapeutic gene into the body in what’s called an in vivo process.
In Phase 1 clinical trial results that Avrobio released last fall, the company said that within 45 days of receiving AVR-RD-01, the enzyme level of the Fabry disease patient in the study rose to the range of a person who does not have the disease. The company added that the patient’s enzyme levels remained in that range at the six-month mark. Avrobio reported no side effects during the trial.
Though gene therapy offers the potential of a long-lasting treatment, and perhaps even a cure for some diseases, scientists are still learning about possible risks of the technology. On Tuesday, gene therapy pioneer James Wilson and his colleagues at the University of Pennsylvania published a paper detailing nerve and liver damage that occurred in two separate animal studies testing an experimental gene therapy for spinal muscular atrophy. Those findings rattled the stock prices of several gene therapy developers.
MacKay says the ex vivo, lentiviral gene therapy developed by his company and some others has a strong safety record based on tests in more than 200 patients. He added that Wilson’s findings for in vivo, AAV gene therapies are not related to Avrobio’s approach.
“The learning and understanding on that topic is evolving by the day with the data disclosed [Tuesday],” Mackay says. “The point that we would make is it’s an AAV issue that needs further elucidation and it’s an AAV issue that may be related to a higher dose. It has no bearing on ex vivo lentiviral gene therapy.”
Avrobio also received funding in the Series B round from Aisling Capital, Brace Pharma Capital, Eventide, Morningside, and Leerink Partners, along with earlier investors Atlas Venture, SV Health Investors, and Clarus Ventures. Besides financing Phase 2 testing of the Fabry disease gene therapy, MacKay says the capital will support the company’s work on gene therapies for three other lysosomal storage disorders. The company aims to bring potential treatments for cystinosis and Gaucher disease into clinical trials. The cash will also finance more pre-clinical research for a Pompe disease gene therapy.
Avrobio last raised money in 2016, a $25 million Series A round that the company used to bring the Fabry disease gene therapy into Phase 1 testing. MacKay won’t say how far the latest funding round will take the company. Asked whether an initial public offering is planned, MacKay acknowledged that the company will need additional financing down the line, but it’s not yet clear what form it could take.
DNA image by Depositphotos.