Kodiak Sciences has enrolled the first patients in ALTO, a global phase 3 trial evaluating KSI-501, an investigational bispecific therapy targeting vascular endothelial growth factor (VEGF) and interleukin 6 (IL-6), in patients with diabetic macular edema (DME).

The randomized, double-masked study is designed to test the superiority of KSI-501 5 mg over aflibercept 2 mg (Eylea; Regeneron). Approximately 910 treatment-naïve or previously treated patients will be randomized to 1 of 3 groups: KSI-501 every 8 weeks with monthly assessment for additional individualized dosing, KSI-501 at individualized intervals ranging from every 4 to 24 weeks, or aflibercept every 8 weeks. Patients will be followed for approximately 96 weeks. The primary endpoint is mean change in best-corrected visual acuity from baseline to the average of weeks 48 and 52. A key secondary endpoint will assess the proportion of patients achieving a 2-step or greater improvement on the Diabetic Retinopathy Severity Scale at week 48.

KSI-501 combines a VEGF-trap component with an anti–IL-6 antibody and is intended to address both vascular permeability and inflammatory signaling in DME.

ALTO is the second registrational phase 3 study of KSI-501, following the DAYBREAK trial in neovascular age-related macular degeneration. Kodiak Sciences said that topline data from the 1-year primary endpoint for DAYBREAK are expected in September 2026. RP