Innovent Biologics, Inc. announced that the first participant with neovascular age-related macular degeneration (nAMD) has been successfully dosed in the phase 1 clinical trial of IBI333, a recombinant anti-VEGF–A and anti-VEGF-C bispecific fusion protein. This phase 1 study(CTR20222674)aims to evaluate the safety and tolerability of intravitreal injection of IBI333 in participants with nAMD. IBI333 is a recombinant anti-VEGF-A and anti-VEGF-C bispecific fusion protein independently developed by Innovent.

It can simultaneously bind and neutralize the activities of VEGF-A and VEGF-C. Compared with anti-VEGF-A agents, IBI333 can inhibit the compensatory increased activity of VEGF-C, thus achieve a more sufficient blockage of the VEGF/VEGFR signaling, implying the potential to obtain a more desirable outcome of angiogenesis inhibition and vascular leakage reduction. Age-related macular degeneration (AMD) is a chronic progressive disease in which the focus involves the retina of the macular area, resulting in central visual impairment. nAMD is a subtype of advanced AMD characterized by the presence of choroidal neovascularization and vascular leakage, accounting for 80% to 90% of severe visual loss caused by AMD.

The incidence of AMD is increasing year by year in China and has now leapt to the third leading cause of blindness in China. The pathological mechanism of AMD has not been fully elucidated, and it is generally recognized that angiogenesis induced by increased VEGF expression is the main cause of nAMD pathogenesis. Intravitreal injection of anti-VEGF agents is currently the standard treatment for nAMD.

IBI333 is a recombinant anti-VEGF-A and VEGF-C bispecific fusion protein that is independently developed by Innovent. It consists of three parts: a peptide domain derived from vascular endothelial growth factor receptor, a Fc functional region of human IgG1 and an anti-VEGF-C single-domain antibody. IBI333 can block VEGF–A–mediated signaling pathway to inhibit vascular endothelial cell proliferation, thereby inhibiting angiogenesis and reducing vascular leakage.

Meanwhile, IBI333 can also reduce the epithelial cell window formation induced by VEGF-C, further reduce vascular permeability, and inhibit the binding of compensatory up-regulated VEGF-C to endogenous VEGF receptors, achieving a more comprehensive and effective blocking of intraocular VEGF signaling.