Innovent Biologics, Inc. announced that the first patient with diabetic macular edema (DME) has been successfully dosed in the Phase 1 study of IBI324, a potential first-in-class ophthalmic recombinant human anti-VEGF-A and anti-Ang-2 bispecific antibody. This Phase 1 dose escalations study (CTR20221524) aims to evaluate the safety and tolerability of intravitreal injection of IBI324 in subjects with diabetic macular edema (DME). IBI324 is a dual-target specific recombinant fully humanized anti-VEGF-A and anti-Ang-2 bispecific antibody developed by Innovent, which can achieve anti-angiogenesis, vascular stabilization and inflammation inhibition by blocking both VEGF-A and Ang-2, aiming to bring more potential clinical benefits to DME patients, such as prolonging the dosing interval and improving treatment compliance.

Diabetic retinopathy is a complication of diabetes, caused by high blood sugar levels damaging the retinal microvascular, DME is a chronic progressive disease that causes impaired vision or even blindness due to swelling of the central part of the retina. The incidence of diabetic retinopathy has gradually increased, and it is also one of the main causes of blindness in working-age adults and the elderly1, which seriously affects the quality of life of diabetic patients, and places a heavy financial burden on society2. Hyperglycemia and associated metabolic pathways, oxidative stress as well as inflammation in diabetes are thought to be closely related to the pathogenesis of diabetic retinopathy and DME, which can lead to neurodegeneration, early microvascular damage, and damage to the neurovascular unit3.

In this state, VEGF expression is upregulated, leading to neovascularization, disruption of vascular endothelial cell integrity, and vascular leakage caused by damage to the blood-retinal barrier; Ang-2, by binding Tie2 receptor on vascular endothelium, can disrupt the stability of the endothelial cell layer and cause leakage4, which acting in combination with VEGF leads to the development of DME. IBI324 is a bispecific anti-VEGF and anti-Ang-2 recombinant fully humanized antibody independently developed by Innovent Biologics. The N-terminus can block VEGF-A-mediated signaling pathway and inhibit the growth and proliferation of vascular endothelial cells, thereby inhibiting angiogenesis, reducing vascular permeability and vascular leakage; the C-terminus of IBI324 is an Ang-2 binding domain independently screened by Innovent that can specific inhibit the binding of Ang-2 to Tie-2 receptor, and therefore improve the sensitivity to other inflammatory factors, further stabilize blood vessels and inhibit vascular leakage.

IBI324 can inhibit neovascularization and stabilize blood vessels and inhibit inflammation that mediated by VEGF-A and Ang-2, which may bring more clinical benefits to patients with DME.