Roche wades deeper into RNA waters, paying Ascidian $42M to develop exon editing drugs

Roche has added to its flotilla of RNA alliances, handing Ascidian Therapeutics $42 million upfront to use an alternative to gene editing to treat neurological diseases. The agreement includes up to $1.8 billion in milestones.

Ascidian is at the forefront of efforts to treat disease by rewriting mRNA. Rather than change DNA, as happens in gene editing, Ascidian edits RNA exons. During the transcription of DNA into RNA, exons are spliced together to form mRNA that is then translated into protein. Mutations in the exons can result in malformed, disease-driving proteins. Ascidian wants to replace mutated exons to treat disease.

The Boston-based biotech delivers DNA constructs, using a range of vehicles, which are transcribed into exon RNA, driving the production of full length, healthy proteins. Like gene therapy, the approach could enable the one-time treatment of disease. Robert Bell, Ph.D., head of research at Ascidian, explained to Fierce Biotech in an interview why a drug developer may want to take that approach rather than edit the gene at the root of a disease. 

“Number one is we can edit at the kilobase scale, thousands of bases of RNA, with one therapeutic modality. When you think about genes that are very large, and genes that are large and have very high mutational variance, one exon editor construct could be applicable to a very broad patient population,” Bell said.

The second core advantage is the platform can make edits without using foreign bacterial or engineered enzymes. Rather, Ascidian relies on existing molecular machinery. Bell said the approach “takes away some of the complexities” inherent in certain gene-editing technologies, which can require multiple vectors and multiple pieces of editing machinery to come together in a target cell. 

Ascidian’s lead candidate is a retinal disease program targeting the genetic cause of Stargardt disease but the biotech has also applied the platform to neurological conditions in earlier-stage tests. The broader potential of the platform informed talks with potential partners including Roche, which stepped up its interest in a deal after seeing Ascidian navigate an important early regulatory test. 

“The scientific discussion really accelerated after we got FDA feedback and opened our IND for Stargardt disease. Now, RNA exon editors have a path to the clinic,” Dan Rosan, chief financial and business officer at Ascidian, told Fierce. “We settled on a really discrete set of targets with very, very high unmet need, where Roche can bring excellent delivery capabilities, disease biology capabilities, and we can combine that with the RNA exon editing platform to make a drug.” 

Roche is making an initial payment of $42 million and committing to up to $1.8 billion in research, clinical and commercial milestone payments to secure exclusive rights to Ascidian’s technology for undisclosed neurological targets. Ascidian will work with Roche on discovery and certain preclinical activities, before handing full control to the Swiss drugmaker for further preclinical work and beyond. 

The deal leaves Ascidian free to go after other targets within neurology, something that was important to the biotech as its researchers continue to explore the potential of the platform. Ascidian is working on its next set of development candidates, which it plans to take into early clinical trials itself, and still has the appetite and capacity for further deals. Interested? Then Ascidian wants you to bring more than money.

“We want folks with a deep commitment to gene editing and genetic disease as a core of their strategy, folks who bring things like manufacturing expertise, delivery expertise, disease biology expertise,” Rosan said. “It's not going to be the same answer for each genetic target. But, in all cases, we will be guided by who we think is the most likely to improve the probability of converting that idea into a drug.”

Roche’s commitment to the RNA space is clear. The Big Pharma teamed up with Arrakis Therapeutics and Ribometrix to develop RNA-targeting small molecules in 2020 and 2021, respectively. Later in 2021, Roche partnered with Shape Therapeutics on RNA editing. The series continued in 2024, when the Swiss drugmaker hooked up with Remix Therapeutics.