Biotechnology company 4D Molecular Therapeutics has drawn another pharmaceutical partner, announcing Monday a licensing agreement with Japan’s Astellas Pharma.
The deal gives Astellas the right to use technology created by 4D in developing a treatment for at least one rare single-gene eye disease. Astellas has options, for additional fees, to add two more genetic targets to the collaboration.
Started nearly a decade ago, 4D specializes in the engineered viruses researchers and drugmakers use to deliver gene therapies into the body. While many types of these viruses can be found in nature, 4D and other companies have been working to invent specially built versions that can, for example, better get into specific cells.
One made by 4D, dubbed R100, caught Astellas’ attention and is the focus of Monday’s deal. Built from an adeno-associated virus, it’s designed to more effectively shuttle genes into the retina.
Astellas will pay 4D $20 million upfront to use the R100 vector, which it will pair its own genetic payload. The pharma will conduct all subsequent research and development, as well as have responsibility for manufacturing or any commercialization that follows.
“After going through different discussions we felt that the best place for us to start a relationship is in ophthalmology with our R100 intravitreal vector and to branch out from there,” said David Kirn, co-founder and CEO of 4D.
The company has run into setbacks, however. Four trial volunteers died in a study of an Audentes gene therapy for X-linked myotubular myopathy, and testing remains on hold. Another trial of a separate therapy was also put on pause, but was cleared to resume earlier this year.
The volunteers’ deaths were linked to signs of liver damage — an area of concern more broadly for gene therapies, many of which end up passing through the liver in some fashion.
“I think there is, of course, exciting progress on gene therapy, but the challenge is really how are you going to deliver outside the liver,” said Morten Sogaard, president and division head of research and technical operations at Astellas’ gene therapy unit.
Specialized vectors like those 4D has created could show a way forward. The R100 vector at the center of Monday’s deal is specific to the eye, which is immune protected and doesn’t involve the same liver risks as targeting other organs.
R100 is delivered via intravitreal injection, a less invasive procedure than the subretinal injections used for other eye gene therapies, like the approved blindness treatment Luxturna. Subretinal injections require surgery under anesthesia and can risk tears or other damage to the retina.
By contrast, intravitreal injections are a much shorter, outpatient procedure. The R100 vector allows this kind of delivery as it’s designed to cross the eye’s internal limiting membrane barrier.
“At the end of the day, we're here to do good for patients, and some wonderful new gene therapies that will help a lot of patients is what we’re hoping to get out of it,” said Sogaard.
Per deal terms, 4D is eligible to receive milestone and option fees of up to $942.5 million, as well as royalties on any approved products that result from the collaboration. The biotech said it’s continuing to develop its gene therapy tools and is open to other potential partnerships in the future.