Looking to spark an antibody-like revolution for RNA interference medicines, City Therapeutics has landed a nearly $100 million series B to fund a clinical push and power further development of its foundational platform.
New investors Viking Global Investors, Sofinnova Investments, Casdin Capital and NYBC Ventures arrived at City's gates to participate in the raise, alongside existing backers like Regeneron Ventures, Arch Venture Partners and Fidelity Management & Research.
City broke ground in 2024 with the backing of RNAi pioneers from Alnylam Pharmaceuticals, like John Maraganore, Ph.D., Mark Keating, M.D. and Tracy Zimmermann, Ph.D.
With eight approved RNAi drugs and hundreds more in the clinic, City CEO Andy Orth told Fierce Biotech that the modality is primed to revolutionize medicine in the same way antibodies once did.
“The underlying belief set here is this is going to be a really meaningful class of medicines,” Orth said. “Within that, just like within the antibodies, there's room for innovation.”
While City’s three wholly owned programs, including a lead phase 1 candidate targeting the blood-clotting protein Factor XI, aim for the liver the same way existing RNAi drugs do, Orth said the biotech is poised to innovate into new tissue types.
“It's going to be all about extra-hepatic delivery of this technology,” the chief exec said. “Less than 5% of the programs in the clinic today are extra-hepatic. That's going to change very rapidly, and that's where City is positioning itself to really leapfrog the competition.”
City’s approach to bringing RNAi outside the liver is all in the name. “City” is actually an acronym that stands for cleavage-inducing tiny RNA. Making RNA molecules themselves smaller, more flexible and less charged should help the company shuttle them into tough-to-reach areas like the central nervous system, Orth said.
“We're at the early days still of proving this out, but we expect these molecules to start showing up in our pipeline and our programs as early as 2027,” Orth explained.
But before then, City should now have enough cash to last through 2027 and advance its current candidates through clinical development. The lead Factor XI candidate should read out its first phase 1 data in the fourth quarter of this year, Orth said, and a phase 2 trial is expected to kick off this year as well.
City’s plan is to pursue Factor XI silencing in patients unable to be treated with existing anticoagulants that target a similar protein called Factor Xa, due to the risk of bleeding, Orth said.
“There is very large patient population that is simply contraindicated for these direct oral anticoagulants, because of that bleed risk,” he told Fierce. These patients, he said, would be ideal recipients of a twice-yearly RNAi injection that shuts down Factor XI, which is known to be a safe target to knock out.
“There are human beings walking around all over this planet with 95% Factor XI deficiency,” Orth said. “They're fine, but they have much fewer strokes and other thromboembolism events than anybody else, so great genetic proof.”
But even a $99.5 million haul can run out quickly if both clinical development and platform science need to move ahead in tandem. But City has plans to supplement the raise by seeking out partnerships, like those it has already inked with Bausch + Lomb and Biogen.
Both of these deals serve as a source of income while also allowing City to expand its platform prowess, Orth said, adding that he expects to forge similar new pacts throughout the next year.
This hunger for partnership even extends to the Massachusetts biotech’s lead candidate, which Orth thinks stands apart in the crowded Factor XI marketplace.
“In the space right now, there are small molecules, antibodies and RNAi programs,” he said. “We're convinced that our molecule is the best, most potent, and most specific or cleanest RNAi program out there. So that may be a partner candidate for us at some point in the future.”