“We can probably edit almost any gene, but that doesn’t mean we should,” Dan Rosan, chief financial and business officer of Ascidian Therapeutics, told Fierce Biotech.
That thinking has shaped how the Boston biotech evaluates potential partnerships around its RNA exon editing platform. Ascidian is not looking to apply the technology everywhere it can, Rosan said, but in areas where it could create “a really differentiated clinical profile.”
Eli Lilly appears to have cleared that bar. The companies have signed a research collaboration worth up to $1.9 billion, giving Lilly the chance to discover and develop RNA exon editing therapeutics for genetic kidney diseases.
The deal combines Ascidian’s RNA exon editing product engine with Lilly’s genetic medicines and renal disease expertise. Ascidian did not disclose the upfront payment, but said the deal could be worth up to $1.9 billion through that payment, development and commercial milestones, plus tiered royalties on worldwide sales.
“Being able to partner with Lilly, which not only has genetic medicines expertise but has significant experience both in preclinical, clinical and commercial products in the renal disease space, helps give us the confidence that if we build this best-in-class payload, we’re partnering with somebody who’s going to be able to advance it to patients,” Ascidian Chief Scientific Officer Robert Bell, Ph.D., told Fierce Biotech.
Ascidian’s platform is designed to edit RNA, rather than DNA, by excising disease-causing exons and replacing them with wild-type exons in vivo. The goal is to restore normal protein production without directly modifying the genome.
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The platform uses the cell’s natural splicing machinery without introducing foreign enzymes, a design meant to reduce risks associated with direct DNA editing and gene replacement. That approach helped Ascidian earn a spot on Fierce Biotech’s 2024 Fierce 15 list.
Bell said the company has focused on four core areas: genes that are too large to package into a single AAV vector, genes with high mutational variance, genes with narrow therapeutic indexes and dominant disorders, where the same reaction could reduce toxic proteins while restoring wild-type protein.
“The platform is applicable across a very broad, diverse set of both genetic and non-genetic disorders,” Bell said.
The kidney disease-focused collaboration between Ascidian and Lilly will have Ascidian lead discovery and selected preclinical activities, while Lilly takes responsibility for additional preclinical work, clinical development, manufacturing and commercialization of any potential products.
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Kidney disease affects an estimated 35.5 million Americans, according to the American Kidney Fund, and inherited forms are part of that burden. The group has also said research has identified more than 600 genetic diseases that can directly or indirectly affect kidney function.
“The reality is that the unmet need and the amount of people living with inherited kidney diseases justifies starting to apply innovative genetic medicine technology such as RNA exon editing to these problems,” Bell said. “Many of the genetic kidney diseases are outside of the scope for conventional gene therapy, or they have too many mutations, so it fell squarely into the sweet spot of what RNA exon editing can do.”
The Lilly pact follows Ascidian’s 2024 partnership with Roche, which included $42 million upfront and up to $1.8 billion in research, clinical and commercial milestone payments to develop RNA exon editing therapeutics for neurological diseases.
The two deals give Boston-based Ascidian major pharma partners in two complex areas: Roche in neurology and Lilly in genetic kidney diseases. Roche has also made a series of RNA-focused bets in recent years, including collaborations with Arrakis Therapeutics, Ribometrix and Remix Therapeutics.
Lilly, meanwhile, entered a 2025 deal with MeiraGTx for the retinal gene therapy AAV-AIPL1, paying $75 million upfront with more than $400 million in potential milestone payments. Last month, Lilly also signed a pact with Profluent Bio worth up to $2.25 billion to develop AI-designed recombinases for genetic medicines.
Ascidian is balancing its collaborations with the development of its wholly owned lead asset, ACDN-01, which targets Stargardt disease, one of the most common forms of inherited blindness and a disease with no approved treatments. Like conventional retinal gene therapies, ACDN-01 is delivered via AAV, but rather than replacing a gene, the payload is designed to edit RNA by replacing disease-causing exons without modifying the underlying genome.
The candidate is in a phase 1/2 clinical trial and has received Fast Track and Rare Pediatric Disease designations from the FDA. Ascidian says ACDN-01 is the first RNA exon editing clinical candidate tested in humans. Adult dose escalation has been completed in the STELLAR trial, and early safety data have allowed Ascidian to expand the study into additional adults and begin dosing pediatric patients.
Rosan said the Stargardt program is one that Ascidian can prosecute on its own because the disease biology and delivery path for retinal genetic medicines are relatively well understood. That calculus changes in areas such as neurology and kidney disease, where drug development and delivery challenges may call for a larger partner.
“In the renal disease space, unpacking how you deliver a genetic medicine to the kidney is also really, really difficult,” Rosan said. “We anticipate that it will be one of the core problems that we’re going to work on with our partners.”
That is why Ascidian is being selective about when to go alone and when to partner, Rosan said.
“There are assets where they will do better in the hands of a collaboration between an innovative biotech and a big pharma than they would in the hands of the innovative biotech by itself,” Rosan said. “Our philosophy really starts with: Who’s the best owner of the asset at any given time?”
