Key Takeaways

  • The first participant has been dosed in a phase 1 trial of CITY-RBP4 for Stargardt disease, with initial data expected in mid-2027

  • The randomized, placebo-controlled study will assess safety, tolerability, pharmacokinetics, and RBP4 suppression following subcutaneous administration

  • CITY-RBP4 targets vitamin A transport to the eye and is also being explored as a potential treatment for geographic atrophy

City Therapeutics announced that the first person has been dosed in a phase 1 clinical trial evaluating CITY-RBP4, an investigational RNA interference (RNAi) therapeutic candidate for Stargardt disease type 1. The company expects to report initial trial data in mid-2027.

CITY-RBP4 is designed to silence expression of retinol-binding protein 4 (RBP4), potentially reducing vitamin A delivery to the eye and slowing retinal damage and vision loss associated with Stargardt disease. The first-in-human, multicenter, randomized, double-masked, placebo-controlled trial will evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple subcutaneous doses of CITY-RBP4 in healthy volunteers and patients with Stargardt disease.

Pharmacodynamic assessments will measure RBP4 suppression and associated reductions in circulating retinol. Patients with Stargardt disease may also enroll in a planned open-label extension study evaluating long-term safety and preliminary efficacy, including exploratory retinal imaging and visual function assessments.

Stargardt disease is an inherited macular degeneration caused by mutations in the ABCA4 gene, resulting in the accumulation of toxic vitamin A byproducts in the retina and progressive, irreversible central vision loss. There are currently no approved treatments.

CITY-RBP4 is a GalNAc-conjugated small interfering RNA therapeutic designed to suppress hepatic RBP4 expression. Preclinical studies demonstrated durable RBP4 suppression and reductions in circulating retinol, while pharmacodynamic modeling suggests the potential for infrequent subcutaneous administration.

City Therapeutics is also exploring CITY-RBP4 for geographic atrophy secondary to age-related macular degeneration, which shares pathological features involving toxic vitamin A byproduct accumulation.

The trial marks the company's second clinical-stage program, with a third program expected to enter clinical testing through an investigator-initiated trial by year-end.