Odesivimab

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.

Odesivimab is a fully-humanized IgG1κ monoclonal antibody (mAb) directed against the EBOV GP1,2 glycoprotein, which binds within the "chalice" structure near the GP head in partial contact with the glycan cap with a binding affinity (KD) of between 8.26 and 8.42 nM. Odesivimab exhibits weak (<50%) neutralization of chimeric lentiviral particles expressing EBOV GP1,2 and is able to bind soluble GP1,2. In addition, Odesivimab 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 1.6 nM. Combined with Maftivimab and Atoltivimab, Odesivimab works to block EBOV cell infection and lysosomal escape, as well as the potential antibody-dependent cell-mediated killing of EBOV-infected cells.