Dive Brief:
- Italy-based biotechnology startup AAvantgarde on Tuesday raised 61 million euros, or about $65 million, to develop a pair of technologies meant to address a key limitation of gene therapy treatments.
- The Series A funding, co-led by Atlas Venture and Forbion, will support the advancement of experimental gene therapies for two inherited retinal disorders: Stargardt disease and retinitis pigmentosa associated with a form of Usher syndrome. The Stargardt treatment is headed towards clinical testing, and the new financing will help complete a proof-of-concept study for the Usher syndrome therapy in humans, the company said.
- The two treatments are testing different ways to use adeno-associated viruses, or AAVs, to deliver larger corrective genes into the body. AAVs are widely used in gene therapy experiments and involved in most of the marketed genetic medicines for inherited disorders, but are constrained by their small size, making many diseases difficult to reach.
Dive Insight:
Since 2017, the Food and Drug Administration has approved six gene therapies for inherited conditions. Two more, for Duchenne muscular dystrophy and hemophilia A, could be cleared within weeks, and top FDA officials are expecting that number to climb in the years ahead.
A majority of those treatments rely on AAVs to deliver genetic material into cells, as they’ve been safely used in scores of gene therapy studies and can be administered conveniently through an intravenous infusion. Yet the limitations of AAV gene therapy have become increasingly clear as well, creating opportunities for biotech startups that can address them.
AAVantgarde is specifically going after one of those restraints — the tiny packaging capacity of AAVs. Because the viruses can only carry a small amount of genetic cargo, some genes are too large to fit, forcing developers to find creative solutions. The Duchenne treatment nearing approval, for instance, involves a gene that was trimmed down to fit into an AAV — alterations that have led regulators to question its effects. Several inherited retinal diseases are caused by mutations to large genes, too.
AAVantgarde, spun out of the work of gene therapy specialist Alberto Auricchio, is advancing two strategies meant to sidestep those types of problems. Both of them involve using twin types of viruses to deliver portions of a larger gene into a target cell. To treat this specific type of retinitis pigmentosa, the startup is using “dual hybrid” AAVs carrying instructions for a gene tied to Usher syndrome. For Stargardt, it’s splitting a large sequence for a therapeutic protein into smaller parts and stuffing them, along with other materials, into separate AAVs.
AAVantgarde is hoping these approaches will enable large, therapeutic genes to be conveniently delivered into tissues and cells, “something that could extend into many disease areas,” said Atlas partner and new board member Jason Rhodes, in a statement.
The startup is led by Natalia Misciattelli, a former senior executive at publicly traded gene therapy developer Freeline Therapeutics. It was seeded and incubated by Sofinnova Partners.