CAMBRIDGE, Mass. — City Therapeutics, Inc., a biopharmaceutical company leading the future of RNA interference (RNAi)-based medicine, presented preclinical data for CITY-RBP4, a potentially first-in-class RNAi therapy for the treatment of Stargardt disease, in an oral session today at the Association for Research in Vision and Ophthalmology (ARVO) 2026 Annual Meeting.
Stargardt disease type 1 (STGD1), the most prevalent form of inherited macular degeneration, is caused by ABCA4 mutations that lead to the buildup of toxic retinoid by-products in the retina, causing irreversible vision loss. Most patients develop symptoms during childhood and become legally blind in their mid-20s. CITY-RBP4 is designed to silence hepatic expression of RBP4, the vitamin A (retinol) carrier, to potentially slow or halt disease progression. Data in non-human primates show that CITY-RBP4 suppressed RBP4 and reduced circulating retinol by approximately 90% at a 3 mg/kg dose, with a duration consistent with quarterly or biannual dosing in humans. Additionally, the levels of A2E, the primary toxic retinoid by-product, were reduced to normal levels in Stargardt mice using an siRNA specific for murine RBP4.
“Reducing retinol delivery to the eye as an approach to Stargardt treatment has long been an area of interest,” said Tracy Zimmermann, Ph.D., chief scientific officer of City Therapeutics. “We are encouraged by these early findings showing substantial reductions in both RBP4 and toxic retinoid by-products, which support the continued development of CITY-RBP4 to improve outcomes for people with STGD1.”
RNAi therapeutics including CITY-RBP4 are designed to enable consistent, sustained target suppression and support less-frequent dosing and improved adherence versus other drug modalities. City Therapeutics plans to submit a regulatory application in mid-2026, with plans to initiate a global Phase 1 clinical study in the second half of this year.
“STGD1 is a devastating condition with no approved treatments, and we are encouraged by the potential of CITY-RBP4 to address the underlying disease process,” said Baisong Mei, M.D., Ph.D., chief medical officer of City Therapeutics. “These preclinical data demonstrate the depth, specificity and durability of CITY-RBP4 in suppressing RBP4 in the liver, and we look forward to continuing to explore its therapeutic promise as we enter the clinic in mid-2026.”
About City Therapeutics
City Therapeutics is a biopharmaceutical company harnessing its next-generation RNAi platform to improve and expand the reach of RNAi-based medicines. The company is building a pipeline of innovative RNAi therapeutics to make a significant impact for patients across multiple therapeutic areas. Co-founded by pioneering executives and scientists in RNAi, City Therapeutics is based in Cambridge, MA, and has raised $135 million from leading life sciences investors. For more information, please visit us at www.citytx.com and follow us on X.
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