City Therapeutics, Inc. (Nasdaq: CTY) announced on November 10, 2026, that the first participant has been dosed in a Phase 1 clinical trial of CITY-RBP4. The trial is an investigational RNAi therapeutic candidate designed to treat Stargardt disease type 1, an inherited macular degenerative disease that is the leading cause of central vision loss in children and young adults.
CITY-RBP4 is a GalNAc-conjugated small interfering RNA (siRNA) therapeutic candidate. It is designed to silence hepatic expression of retinol-binding protein 4 (RBP4). By reducing the delivery of vitamin A to the eye, the company aims to slow the progression of retinal damage and vision loss associated with the disease. Preclinical studies demonstrated potent and durable suppression of RBP4 and corresponding reductions in circulating retinol.
The Phase 1 trial is a first-in-human, multicenter, randomized, double-masked, placebo-controlled study. It is being conducted in healthy volunteers and people with Stargardt disease. The study is designed to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple subcutaneous doses of CITY-RBP4. Pharmacodynamic assessments will include suppression of RBP4 and the associated reduction in circulating retinol.
Participants with Stargardt disease enrolled in this study are eligible to be enrolled in a planned open-label extension study. This extension study will evaluate the long-term safety and preliminary efficacy of CITY-RBP4, including exploratory measures such as retinal imaging and visual function assessments.
City Therapeutics expects to report initial data from the Phase 1 trial in mid-2027. The company’s lead development programs include CITY-FXI for thromboembolic diseases, CITY-RBP4 for Stargardt disease, and CITY-TFR2 for anemia associated with chronic diseases.
