City Therapeutics closes $99.5M Series B for RNAi pipeline
What's the deal? City Therapeutics, a California biotech developing next-generation RNA interference medicines, has closed a $99.5M series B round. Backers include Regeneron VenturesDealroom has a profile for this one. Try Dealroom →, ARCH Venture Partners, Rock Springs CapitalDealroom has a profile for this one. Try Dealroom →, and new investors Sofinnova InvestmentsDealroom has a profile for this one. Try Dealroom → and Viking Global InvestorsDealroom has a profile for this one. Try Dealroom →.
The funds will advance City's pipeline, starting with its lead asset CITY-FXI — a therapy designed to prevent dangerous blood clots without increasing bleeding risk. CITY-FXI targets the coagulation protein Factor XI and is in Phase 1 development for thromboembolic diseases.
City is also working on a therapy for Stargardt disease and three other undisclosed targets, though none of those programmes have entered the clinic. Part of the raise will go toward its next-generation RNAi engineering platform and unspecified business development activities.
Why now? City launched in October 2024 with $135M in series A funding, bringing its total raise to roughly $235M in under a year. The company is led by John MaraganoreDealroom has a profile for this one. Try Dealroom →, former chief executive officer of AlnylamDealroom has a profile for this one. Try Dealroom → and a heavyweight in RNA therapeutics, who co-founded City and serves as executive chairman.
Momentum has been building fast. In May 2025, BiogenDealroom has a profile for this one. Try Dealroom → signed a research partnership worth up to $1B to co-develop an RNAi therapy for an undisclosed central nervous system disease — a significant validation of City's platform. The company also made BioSpace's NextGen class of 2026, ranking among the industry's most promising early-stage players.
What could go wrong? Most of City's pipeline is preclinical, with only CITY-FXI in Phase 1. The biotech's core bet — that RNAi can be delivered effectively beyond the liver — remains technically challenging and largely unproven at scale.
RNAi medicines have historically been limited to liver targets, and expanding to other tissue types introduces significant delivery hurdles. City's platform uses "trigger molecules" paired with targeting ligands to reach a wider range of tissues, but clinical proof is still early.
The signal: Raising roughly $235M in under a year — and attracting crossover investors like Viking Global Investors alongside deep-sector specialists such as ARCH Venture Partners and Sofinnova Investments — underscores how quickly capital is converging on extra-hepatic RNAi as a distinct investment thesis. Biogen's billion-dollar partnership adds big-pharma validation, suggesting that the incumbents see City's trigger-molecule approach as a credible path to unlocking tissue types the first wave of RNAi companies could not reach.
Read more: BioSpace
