ADI-15742

ADI-15742 is a human monoclonal antibody isolated from an Ebola virus disease survivor that exhibits broad and potent neutralizing activity against all known ebolaviruses by targeting a highly conserved epitope at the base of the viral glycoprotein fusion loop. It binds the internal fusion loop/fusion peptide region spanning GP1 and GP2 subunits across neighboring protomers, recognizing a pan-ebolavirus-conserved site of vulnerability and neutralizing both uncleaved and endosomally cleaved GP species with sub-nanomolar potency in pseudotyped and authentic virus systems. Structural and functional studies show that ADI-15742 is clonally related to ADI-15878 and, like that antibody, can act late in the entry pathway by engaging cleaved GP in NPC1-positive endosomes, thereby blocking the membrane fusion step and providing robust protection in small-animal models of multiple ebolavirus species.[1][5][9][11][12]