Gene therapy developers are on bit of a roll. Last week saw the release of promising data on gene therapies for hemophilia and the acquisition by Pfizer of a startup dedicated to the technology. And now another recently launched company, Avrobio, just grabbed a $25 million round of funding.
The Cambridge, MA-based company was formally launched in February, and today secured a Series A round co-led by Atlas Venture, Clarus, and SV Life Sciences. Like a growing number of companies, Avrobio aims to use gene therapy—a method of shuttling genetic fixes into the body to provide long-lasting, if not permanent treatments—to go after rare diseases.
One of Avrobio’s programs, for instance, is for Fabry disease, a rare disorder characterized by the abnormal buildup of a dangerous fatty substance in cells, which can cause kidney failure, heart attacks, and other serious medical problems. Fabry is currently treated with enzyme replacement therapy is, and more recently, Amicus Therapeutics (NASDAQ: [[ticker:FOLD]]) won approval in Europe for a pill, migalastat (Galafold), for a genetic subset of Fabry patients. But gene therapy’s promise is its durability in as little as a one-time procedure, which for Fabry patients could mean no more frequent trips to infusion centers. Additionally, many patients can’t tolerate ERTs, and others see their condition get worse even with treatment.
Avrobio also aims to go where many other gene therapy companies of recent vintage haven’t—cancer. Its other experimental treatment is for the blood cancer acute myeloid leukemia. Of the gene therapy companies to emerge over the last several years, only Bluebird Bio (NASDAQ: [[ticker:BLUE]]) has tried to use gene therapy to treat cancer. It has a multiple myeloma therapy in early testing as part of a partnership with Celgene (NASDAQ: [[ticker:CELG]]).
There are two main types of gene therapy: in vivo process, in which a therapeutic gene is introduced into the patient’s body; and an ex vivo variety, in which patients’ stem cells are harvested, and equipped with a healthy version of a gene, and then infused back into the body. In vivo therapy is currently the much more common approach, pursued by companies such as Spark Therapeutics (NASDAQ: [[ticker:ONCE]]), BioMarin Pharmaceutical (NASDAQ: [[ticker:BMRN]]) and UniQure (NASDAQ: [[ticker:QURE]]). Spark’s experimental treatment for a genetic form of blindness uses a delivery tool known as an adeno-associated virus, which has become a staple of in vivo gene therapy. The treatment could be the first gene therapy approved in the U.S., joining two already approved in Europe.
Less common is the ex vivo procedure used by companies such as Bluebird, U.K.-based startup Orchard Therapeutics, and now Avrobio. Through this process, a virus from the lentivirus family that has been genetically modified to be harmless carries healthy genes into stem cells harvested from the patient. The stem cells are then grown in a culture and infused back into the patient, where they are supposed to give rise to more cells with the correct gene.
Bluebird has shown encouraging early results with ex vivo gene therapy for the blood disorders beta-thalassemia and sickle cell disease, and a rare brain disorder called childhood cerebral adrenoleukodystrophy. And now Avrobio aims to use this process to, as president and CEO Geoff MacKay said in a statement, “displac[e] the standard of care” for people with Fabry or AML. A Fabry gene therapy aims to increase the levels of the enzyme needed to prevent the dangerous buildup of the fatty substance. In AML, Avrobio’s goal is to help drive a powerful immune response. After chemotherapy, some of a patient’s remaining cancer cells would be extracted and modified to express an inflammatory molecule called interleukin-12. Those cells would then be infused back into a patient, where they’re meant to alert the immune system to kill the remaining AML cells.
That’s the plan, of course; both treatments are currently in Phase 1 trials and have yet to produce data in patients. These drug programs come from work done by immunologist Christopher Paige and scientist Jeffrey Medin at the University Health Network in Toronto.
Atlas partner Bruce Booth chairs Avrobio’s board of directors. Clarus managing director Scott Requadt, and SV partner Josh Resnick have joined the board as part of the funding.
