City Therapeutics Advances RNAi Pipeline as CITY-FXI Enters Clinic and Stargardt Program Approaches IND

City Therapeutics has completed a $99.5 million Series B financing round that will support advancement of its next-generation RNA interference (RNAi) platform and pipeline, including an ongoing phase 1 clinical trial evaluating CITY-FXI for thromboembolic diseases and additional programs expected to enter clinical development later this year.¹

According to the company, proceeds from the financing will be used to advance RNAi therapeutic candidates, further develop its RNAi engineering platform, and support business development activities.¹

What clinical programs are driving city therapeutics’ development strategy?

The company's lead clinical asset, CITY-FXI, recently entered a phase 1 clinical trial. The investigational RNAi therapeutic targets coagulation Factor XI (FXI), a protein involved in thrombus formation that has emerged as an attractive target for anticoagulant development because inhibition may reduce clotting risk while potentially minimizing bleeding complications.²˒³

Several pharmaceutical companies have pursued FXI inhibition strategies in recent years, reflecting growing interest in the pathway as a next-generation approach to anticoagulation.²˒³

In addition to CITY-FXI, City Therapeutics recently reported positive preclinical data for CITY-RBP4, an RNAi candidate designed to treat Stargardt disease. The inherited retinal disorder is among the most common forms of juvenile macular degeneration and currently lacks approved disease-modifying therapies.¹˒⁴

Company leadership stated that the new capital is expected to support the advancement of two programs into clinical development by the end of 2026, including CITY-RBP4.¹

Why Factor XI matters

Current anticoagulants effectively reduce thrombotic events but can increase bleeding risk. Because FXI appears to contribute more to pathologic clot formation than normal hemostasis, researchers have hypothesized that inhibiting FXI could provide antithrombotic efficacy with less bleeding. Several companies are pursuing FXI-targeted approaches across antisense, monoclonal antibody, and RNAi modalities.²˒³

Why Stargardt disease is attractive for RNAi

Stargardt disease is an inherited retinal degeneration that causes progressive central vision loss, often beginning in childhood or early adulthood. With no approved disease-modifying therapies currently available, gene-based approaches including RNAi are being investigated as potential methods to address the underlying molecular drivers of disease.⁴

How is RNAi technology expanding beyond traditional applications?

RNA interference is a naturally occurring cellular mechanism that uses small RNA molecules to selectively suppress the expression of disease-causing genes. Over the past decade, the modality has matured from a promising research concept into a validated therapeutic platform, resulting in multiple approved medicines for genetic, metabolic, and hepatic diseases.⁵

Despite these advances, delivery beyond the liver remains a significant challenge for many RNAi developers. Companies across the sector are investing in new chemistries, targeting approaches, and delivery technologies designed to expand RNAi's reach into additional tissues and disease areas.⁵˒⁶

City Therapeutics was founded by scientists and executives with extensive experience in RNAi drug development and is positioning its platform as a next-generation approach intended to broaden the therapeutic potential of RNAi-based medicines.¹

"This Series B financing reflects our substantial progress and the confidence our investors, both longstanding and new, have in the City Therapeutics team, platform and pipeline," said Andy Orth, chief executive officer of City Therapeutics, in a company statement.¹

Orth noted that the company has advanced CITY-FXI into clinical testing and established strategic collaborations with Bausch + Lomb and Biogen since completing its Series A financing.¹

What does the financing signal for the RNAi therapeutics market?

The financing represents continued investor confidence in RNAi therapeutics despite a challenging biotech funding environment. The sector has attracted increasing attention as clinical validation and regulatory approvals have demonstrated the potential of gene-silencing approaches to address diseases that may be difficult to treat using conventional small molecules or biologics.⁵

John Maraganore, PhD, co-founder and executive chairman of City Therapeutics, stated that the company's platform is designed to extend the capabilities of traditional RNAi technologies and enable expansion into new tissue types and therapeutic targets.¹

References

1. City Therapeutics Announces $99.5 Million Series B Financing to Advance Next-Generation RNAi Therapeutics. (2026 Jun 8). Business Wire. https://www.businesswire.com/news/home/20260608486606/en/City-Therapeutics-Announces-%2499.5-Million-Series-B-Financing-to-Advance-Next-Generation-RNAi-Therapeutics
2. Weitz JI, Fredenburgh JC. (2017 Feb 24). Factors XI and XII as targets for new anticoagulants. Front Med (Lausanne). https://pubmed.ncbi.nlm.nih.gov/28286749/
3. Gailani D, Büller H. (2016). Factor XI as a therapeutic target. Arterioscler Thromb Vasc Biol. https://pubmed.ncbi.nlm.nih.gov/27174099/
4. National Eye Institute. Stargardt Disease. National Institutes of Health. Accessed June 9, 2026. https://www.nei.nih.gov/eye-health-information/eye-conditions-and-diseases/stargardt-disease
5. Setten RL, Rossi JJ, Han SP. (2019 Jun). The current state and future directions of RNAi-based therapeutics. Nat Rev Drug Discov.
6. Hu B, Zhong L, Weng Y, et al. (2020 Jun 19). Therapeutic siRNA, state of the art. Signal Transduct Target Ther. https://pubmed.ncbi.nlm.nih.gov/32561705/