CAMBRIDGE, Mass. — City Therapeutics presented preclinical data for its investigational RNA interference therapy CITY-RBP4, which is being developed as a potential treatment for Stargardt disease.
The Cambridge-based biopharmaceutical company said the data were presented during an oral session at the Association for Research in Vision and Ophthalmology 2026 Annual Meeting.
CITY-RBP4 is designed to silence hepatic expression of retinol binding protein 4, or RBP4, which carries vitamin A, or retinol. The approach is intended to reduce delivery of retinol to the eye and potentially slow or halt progression of Stargardt disease type 1.
Stargardt disease type 1, the most common form of inherited macular degeneration, is caused by ABCA4 mutations that result in the buildup of toxic retinoid byproducts in the retina, leading to irreversible vision loss. City Therapeutics said most patients develop symptoms during childhood and become legally blind in their mid-20s.
In non-human primates, CITY-RBP4 suppressed RBP4 and reduced circulating retinol by about 90% at a 3 mg/kg dose, with durability the company said could support quarterly or twice-yearly dosing in humans. In Stargardt mice, an siRNA specific for murine RBP4 reduced levels of A2E, the primary toxic retinoid byproduct, to normal levels.
“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 such as CITY-RBP4 are designed to provide sustained target suppression and support less frequent dosing than some other drug types. City Therapeutics said it plans to submit a regulatory application in mid-2026 and begin a global Phase 1 clinical study in the second half of the 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.”
