magacizumab

**Magacizumab** is a humanized hinge-stabilized IgG4 monoclonal antibody that functions as a function-blocking agent against leucine-rich alpha-2-glycoprotein 1 (LRG1), a protein promoting pathogenic angiogenesis and vascular dysfunction in conditions like neovascular age-related macular degeneration (wet AMD), cancer, and other retinopathies. Developed from the lead mouse monoclonal 15C4 by researchers at UCL Institute of Ophthalmology, it binds specifically to an epitope on LRG1, preventing its interaction with partners like TGF-β and inhibiting abnormal blood vessel growth without internalization in tested models. Preclinical studies demonstrate efficacy in reducing choroidal neovascularization, tumor growth, and metastasis, with an ADC version (conjugated to MMAE via cleavable linker) showing enhanced antitumor activity comparable to chemotherapy in melanoma models while sparing systemic toxicity.[1][3][5][6]