Human Anti-IFNAR1 Recombinant Antibody (clone MEDI546) (CAT#: PABL-228)

Figure 1 Mean (±SD) serum MEDI-546 concentration.

A. Single IV Administration; B. Multiple IV Administrations. LLOQ, lower limit of quantitation; SD, standard deviation. Mean data below LLOQ are not plotted.

Goldberg, A., Geppert, T., Schiopu, E., Frech, T., Hsu, V., Simms, R. W.,... & Wang, B. (2014). Dose-escalation of human anti-interferon-α receptor monoclonal antibody MEDI-546 in subjects with systemic sclerosis: a phase 1, multicenter, open label study. Arthritis research & therapy,16(1), R57.

Figure 2 Membrane binding of A488-labelled anifrolumab to IFNAR1, and the APC-labelled membrane marker CD11b antibody, on primary human monocytes at 0 and 30min after placing cells under internalisation conditions of 37°C and 5% carbon dioxide (CO2).

Riggs, J. M., Hanna, R. N., Rajan, B., Zerrouki, K., Karnell, J. L., Sagar, D.,... & de los Reyes, M. (2018). Characterisation of anifrolumab, a fully human anti-interferon receptor antagonist antibody for the treatment of systemic lupus erythematosus.Lupus science & medicine, 5(1), e000261.

Figure 3 Anifrolumab inhibits type I interferon (IFN)-induced IFN-stimulated response element (ISRE) signalling.

Type I IFNinduced luciferase activity in HEK293-ISRE reporter cells elicited by (A) recombinant IFN-α2 protein (100 (triangles), 1000 (squares), 10 000 (circles) or 100 000 (diamonds) U/mL); (B and C) CpG-A-stimulated and DNA/IgG–immune complexes (DNAIC)-stimulated pDC supernatant (diluted 1:10 (triangles), 1:100 (squares) or 1:1000 (circles)), with preincubation with anifrolumab (black symbols) or isotype control antibody (white open circles). Type I IFN-induced luciferase activity in pIL5-ISRE reporter cells elicited by sera from patients with SLE with and without preincubation with anifrolumab or isotype control antibody; (D) representative assay with a single serum sample and anifrolumab IC50 of 0.05nM and (E) relative IFN activity of 20 serum samples. Mean IC50 for sera from three patients with SLE was 0.32±0.50nM.

Riggs, J. M., Hanna, R. N., Rajan, B., Zerrouki, K., Karnell, J. L., Sagar, D.,... & de los Reyes, M. (2018). Characterisation of anifrolumab, a fully human anti-interferon receptor antagonist antibody for the treatment of systemic lupus erythematosus.Lupus science & medicine, 5(1), e000261.

Figure 4 Anifrolumab inhibits cytokine production, plasmacytoid dendritic cell (pDC) activation and the type I (interferon gene signature) IFN gene signature.

IFN-α production by CpG-A-stimulated and DNA/IgG–immune complexes (DNA-IC)-stimulated (A) peripheral blood mononuclear cells (PBMCs) and (B) pDCs with and without preincubation with anifrolumab or isotype control antibody. Dose–response curve of antibody inhibition of IFN-α from a representative donor stimulated with (A and B, left panel) CpG-A or (A and B, centre panel) DNA-IC and (A and B, right panel) quantification of IFN inhibition in multiple donors at 10µg/mL (67.7 nM) anifrolumab or isotype control antibody. (C, left panel) Induction of the 21-gene IFN gene signature in CpG-A-stimulated PBMCs from three donors. (C, right panel) Inhibition of the 21-gene IFN gene signature in CpG-A-stimulated PBMCs from seven donors with and without preincubation with anifrolumab or isotype control antibody. (D) CD80 activation and CD83 maturation surface marker expression in CpG-A-stimulated pDCs with and without preincubation with 10µg/mL (67.7 nM) anifrolumab or isotype control antibody. (E) TNF-α, interleukin (IL)-6 and IL-8 secretion from CpG-A-stimulated pDCs with and without preincubation with 10 µg/mL (67.7 nM) anifrolumab or isotype control antibody.

Riggs, J. M., Hanna, R. N., Rajan, B., Zerrouki, K., Karnell, J. L., Sagar, D.,... & de los Reyes, M. (2018). Characterisation of anifrolumab, a fully human anti-interferon receptor antagonist antibody for the treatment of systemic lupus erythematosus.Lupus science & medicine, 5(1), e000261.

Figure 5 Anifrolumab suppresses plasmacytoid dendritic cell (pDC)-dependent plasma cell differentiation.

(A) Representative flow cytometry plots and quantification of plasma cell (CD19+ CD27highCD38high) differentiation in untreated, interleukin (IL)-21- stimulated (positive control) or CpG-A-stimulated B cell/pDC co-cultures. (B) Representative flow cytometry plot and (C and D) quantification of plasma cell differentiation in CpG-A-stimulated B cell/pDC co-cultures with and without preincubation with anifrolumab or control antibody.

Riggs, J. M., Hanna, R. N., Rajan, B., Zerrouki, K., Karnell, J. L., Sagar, D.,... & de los Reyes, M. (2018). Characterisation of anifrolumab, a fully human anti-interferon receptor antagonist antibody for the treatment of systemic lupus erythematosus.Lupus science & medicine, 5(1), e000261.