TY - JOUR T1 - A Humanized Antibody against LRG1 that Inhibits Angiogenesis and Reduces Retinal Vascular Leakage JF - bioRxiv DO - 10.1101/2020.07.25.218149 SP - 2020.07.25.218149 AU - David Kallenberg AU - Vineeta Tripathi AU - Faiza Javaid AU - Camilla Pilotti AU - Jestin George AU - Sterenn Davis AU - Jack WD Blackburn AU - Marie O’Connor AU - Laura Dowsett AU - Chantelle E Bowers AU - Sidath Liyanage AU - Morgane Gourlaouen AU - Alexandra Hoeh AU - Filipa Mota AU - David Selwood AU - James Bainbridge AU - Vijay Chudasama AU - John Greenwood AU - Stephen E Moss Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/07/25/2020.07.25.218149.abstract N2 - Pathological angiogenesis contributes to morbidity in a number of diseases including cancer, diabetic retinopathy and the neovascular form of age-related macular degeneration, leading to significant efforts to develop effective anti-angiogenic therapeutics for these conditions. The field is dominated by inhibitors of vascular endothelial growth factor (VEGF), yet angiogenesis can also be driven and modified by other factors. We have previously demonstrated that leucine-rich alpha-2-glycoprotein 1 (LRG1) contributes to abnormal vessel growth by activating a TGFß switch. Here we report the development and characterisation of a function-blocking fully humanised IgG4 and its Fab fragment, that bind to LRG1 with high affinity and specificity and inhibit vascular leakage in the mouse model of laser-induced choroidal neovascularisation. In summary, we have developed a therapeutic antibody that targets a VEGF-independent signalling axis, which may be effective in a number of conditions either as monotherapy or in combination with other vascular targeted therapies.Competing Interest StatementS.E.M. and J.Gr. are founders of and shareholders in PanAngium Therapeutics that owns the commercialisation rights to Magacizumab and MagaFab. S.E.M., J.Gr. and V.T. are named inventors on patents relating to Magacizumab and MagaFab. V.C. is a Director of the spin-out ThioLogics, but there are no competing financial interests to declare. ER -