Roche has tapped a small Boston startup for access to a sweeping form of RNA editing that replaces large swathes of errant genetic code. Broadly known as RNA writing, scientists have said the technology is akin to replacing whole pages of a book at a time, rather than changing individual letters or words.
The startup, Ascidian Therapeutics, announced Tuesday that it struck a deal with Roche to develop its version of the technology, which it calls RNA exon editing, for neurological diseases. Ascidian will get an initial $42 million and up to $1.8 billion in potential milestone payments.
“We realized this [technology] would have a fairly broad potential,” Ascidian president and CEO Michael Ehlers told Endpoints News in an interview. “The Roche team really understood the science fairly early on.”
Ehlers said that the collaboration could include multiple targets and diseases that the companies have already agreed to work on, but he wouldn’t share details.
The company is developing RNA-based drugs that trick a cell into splicing one or several segments of RNA known as exons in place of an existing stretch of code. Another startup, Amber Bio, and several academic labs have developed similar approaches that rely on CRISPR enzymes to help guide the therapy to the right place.
Ascidian is testing its approach in an inherited form of vision loss called Stargardt disease. Scientists have cataloged more than 1,000 genetic mutations that can cause the condition. Developing individual therapies to treat each of them would be onerous, and the gene is too big to be replaced wholesale. But by designing an RNA writing therapy that replaces the first 22 exons in the gene, Ascidian believes a single treatment could correct the underlying mutations in roughly two-thirds of patients.
In January, the FDA greenlit Ascidian’s request to begin clinical tests using that approach.
Dan Rosan“That validation by the FDA gave a lot of comfort not only to Roche and many potential partners that we had a path to the clinic with this platform,” Ascidian chief financial and business officer Dan Rosan told Endpoints.
It was the first authorization for any form of RNA editing to be tested in humans in the US. Most companies in the field, including Wave Life Sciences and Korro Bio, are developing a form of RNA base editing that tweaks just a single letter of the molecule. But all of them hope that editing short-lived RNA molecules, rather than making permanent changes to DNA, may be safer.
Roche has already struck an RNA editing partnership with Shape Therapeutics focused on RNA-based editing for brain diseases. Ehlers said that a big focus of his company’s discussions with Roche was finding diseases where “RNA exon editing could provide differentiation” compared to other kinds of genetic medicines.
Robert Bell“The categories of disease we can address can really be quite different,” Ehlers said. “There are lots of ways to modify RNA and DNA, but not very many ways to alter thousands of bases at a time, and very few ways to do it without a foreign enzyme.”
Delivering genetic drugs into the nervous system can be a challenge, and Ascidian’s head of research, Robert Bell, told Endpoints that the startup is excited about the next-generation viral vectors that Roche is developing.
“At Ascidian, we decided to just work on the payload,” Bell said. “We are quite confident with Roche’s progress in delivery to the central nervous system.”