Anti-Human IFNy (Emapalumab) (IVMB0493)

IFNγ plays roles in Th1 differentiation, macrophage function, leukocyte migration to sites of infection, and increasing major histocompatibility complex expression to improve T-cellrecognition of infected or malignant cells ¹. Hemophagocytic lymphohistiocytosis (HLH) is a rare but severe dysregulation of the immune system characterized by increased IFNγ production, macrophage and lymphocyte hyperactivity with tissue infiltration, hypersecretion of pro-inflammatory cytokines (CXCL9), hemophagocytosis, tissue damage, and multi-organ failure ². IFNγ plays a central role in the pathophysiology of HLH, and blocking IFNγ leads to clinical improvement.

Emapalumab was developed by Novimmune and Swedish Orphan Biovitrum as an immunotherapeutic treatment for HLH ². Emapalumab is a fully human IgG1 monoclonal antibody that targets and binds to IFNγ with high affinity. Emapalumab neutralizes IFNγ activity and inhibits interaction with its receptor by acting as a non-competitive inhibitor binding to free IFNγ and IFNγ-Receptor-1(IFNγR1)-bound IFNγ. Emapalumab inhibits receptor dimerization and transduction of interferon-γ signaling, impairing the interaction induced by IFNγ at the cell surface with IFNγR1 and IFNγ R2 and thereby neutralizing IFNγ biologic activity ^2,3,4. Emapalumab prevents recruitment of IFNγR2 but has no effect on IFNγR1 endocytosis and internalization into lysosomes ^2,4. In HLH patients, emapalumab reduces the plasma concentrations of the cytokine CXCL9.

Emapalumab is composed of anti-(human IFNγ) human monoclonal NI-0501 heavy chain, disulfide with human monoclonal NI-0501 light chain, dimer ². Emapalumab is produced by recombinant DNA technology and is approximately 148 kDa ⁵.