Atoltivimab

Ebola virus (EBOV) is one of several viruses within the Ebolavirus genus known to infect humans with an average case fatality rate of 43.92%. EBOV particles expose the GP1,2 glycoprotein on their surface, which comprises a trimer of GP1 and GP2 subunit heterodimers, with the subunits connected by a disulfide bond. GP1,2 plays an important role in both cell surface attachment/entry and eventual lysosomal escape through binding to the NPC intracellular cholesterol transporter 1/Niemann-Pick C1 protein (NPC1). In this manner, GP1,2 is integral to the pathogenic cycle of EBOV.

Atoltivimab is a fully-humanized IgG1κ monoclonal antibody (mAb) directed against the EBOV GP1,2 glycoprotein, which binds the GP1,2 glycan cap parallel to the viral surface with a binding affinity (KD) of between 7.74 and 7.84 nM. Atoltivimab exhibits strong (<90%) neutralization of chimeric lentiviral particles expressing EBOV GP1,2 with a half-maximal inhibitory concentration (IC50) value of 0.27 nM. In addition, Atoltivimab is capable of dose-dependent activation of FcγRIIIa signalling in effector cells in the presence of GP1,2-expressing cells with a half-maximal effective concentration (EC50) of 2.9 nM. Combined with Odesivimab and Maftivimab, Atoltivimab works to block EBOV cell infection and lysosomal escape, as well as the potential antibody-dependent cell-mediated killing of EBOV-infected cells.