IBI333

IBI333 is a recombinant anti-VEGF-A and VEGF-C bispecific fusion protein developed by Innovent Biologics for the treatment of neovascular (wet) age-related macular degeneration (nAMD). The molecule consists of three parts: a peptide domain derived from the vascular endothelial growth factor receptor, an Fc functional region of human IgG1, and an anti-VEGF-C single-domain antibody. Its mechanism involves blocking both VEGF-A–mediated signaling to inhibit vascular endothelial cell proliferation and angiogenesis, as well as reducing epithelial cell window formation induced by VEGF-C. This dual inhibition aims to comprehensively block intraocular VEGF signaling, reduce vascular permeability, and address compensatory upregulation of VEGF-C that can occur with standard anti-VEGF therapies. As of April 2025, IBI333 is in phase 1 clinical trials for wet age-related macular degeneration[1][2][5][6].