GNX201

GNX201 (also known as L-HKM4) is a preclinical-stage, protease-activated pro-antibody targeting the Lewis Y (LeY) carbohydrate antigen (CD174), which is overexpressed in various epithelial cancers, including gastric and colorectal cancers. Developed by GlycoNex in collaboration with PrecisemAb Biotech, GNX201 utilizes PrecisemAb's proprietary "Antibody Lock" technology. The antibody is engineered by modifying the N-terminal of the anti-Lewis Y antibody HKM4 with an autologous IgG1 hinge domain (acting as a spatial-hindrance-based lock) connected via a matrix metalloproteinase-2/9 (MMP-2/9)-cleavable linker. This design ensures that the antibody remains inactive in systemic circulation, minimizing on-target, off-tumor toxicities (such as gastrointestinal toxicity). Upon reaching the protease-rich tumor microenvironment, endogenous MMP-2 and MMP-9 cleave the linker, releasing the lock and restoring the antibody's binding and cytotoxic activities (such as ADCC and CDC). GNX201 is also being developed as an antibody-drug conjugate (GNX201-ADC) in collaboration with Nippon Kayaku.

Other names

Lock-HKM4Lock-HKM-4Lock-HKM 4pro-HKM4pro-HKM-4pro-HKM 4pro-antibody GNX201protease-activated anti-LeY antibodyprotease-activated anti-Lewis Y antibody