Iscalimab

Iscalimab (CFZ-533) is a non-depleting IGg1 monoclonal antibody targeting CD40 (KD: 0.3 nM). Iscalimab can be used for research of Graves' hyperthyroidism and autoimmune diseases.

Iscalimab (0.01-1 μg/mL, overnight) blocks rCD154-induced TNF production by primary monocyte-derived dendritic cells (moDCs), with an IC₅₀ of 0.04 μg/mL^[3].
Iscalimab (3 days) inhibits rCD154-induced proliferation of PBMCs from humans, rhesus and cynomolgus animals with IC₅₀s of 0.02, 0.03, and 0.01 μg/mL, respectively^[3].
Iscalimab bind CD40 on B cells from humans, rhesus and cynomolgus animals with EC50 values of approximately 0.2 μg/mL^[3].
Iscalimab (2 μg/mL, 3 h) is internalized by B cells in a CD40-dependent manner^[3].

Iscalimab (150 mg/kg/week, s.c, for 13 weeks) is well tolerated and does not cause any dose-limiting toxicity in rhesus monkeys^[3].
Iscalimab (10 mg/kg, i.v.) completely inhibits T cell-dependent antibody response in Rhesus monkeys^[3].
Iscalimab (30 mg/kg, i.v.) prolongs allograft survival in kidney transplant cynomolgus^[4].

References:
[1]. Kahaly GJ, et al. A Novel Anti-CD40 Monoclonal Antibody, Iscalimab, for Control of Graves Hyperthyroidism-A Proof-of-Concept Trial. J Clin Endocrinol Metab. 2020 Mar 1;105(3):dgz013.
[2]. Flandre TD, et al. Immunosuppression Profile of CFZ533 (Iscalimab), a Non-Depleting Anti-CD40 Antibody, and the Presence of Opportunistic Infections in a Rhesus Monkey Toxicology Study. Toxicol Pathol. 2022 Jul;50(5):712-724.
[3]. Ristov J, et al. Characterization of the in vitro and in vivo properties of CFZ533, a blocking and non-depleting anti-CD40 monoclonal antibody. Am J Transplant. 2018 Dec;18(12):2895-2904.
[4]. Cordoba F, et al. A novel, blocking, Fc-silent anti-CD40 monoclonal antibody prolongs nonhuman primate renal allograft survival in the absence of B cell depletion. Am J Transplant. 2015 Nov;15(11):2825-36.