Crovalimab

Crovalimab (SKY59; RO7112689) is a novel humanized antibody against C5 in a pH-dependent manner with KDs of 15.2 nM and 16.8 μM at pH 7.4 and 5.8, respectively. Crovalimab binds human FcRn with great affinity (KD: 17 μM at pH 6.0). Crovalimab can block cleavage of C5 by the C5 convertase and inhibite the activity of a C5 variant (p.Arg885His). Crovalimab inhibits C5b-9 formation significantly in all three complement pathways, the classical pathway (CP), lectin pathway (LP), and alternative pathway (AP). Crovalimab has the potential for paroxysmal nocturnal hemoglobinuria (PNH) and complement-mediated diseases research.

Crovalimab (SKY59; RO7112689; 0-100 μg/mL) inhibits haemolysis in classical pathway and reactive lysis systems^[2].

Crovalimab (SKY59; RO7112689; 20 mg/kg; iv; only once at day 0) completely prevents accumulation of plasma C5 in cynomolgus monkeys. SKY59-IgG1 (SG115) shows slower clearance: 1.87 mL/day/kg^[1].
Crovalimab (20 mg/kg; iv; a single dose) stably suppressed complement activity in plasma for 8 weeks^[1].
Crovalimab (5 mg/kg by iv at day 0 and 2 mg/kg by sc at day 7, 21, 35, 49, and 63) causes over 20% of serum hemolytic activity in the cRBC lysis assay to correlate with events such as dysphagia and dramatic increases in lactate dehydrogenase (LDH) and alanine aminotransferase (ALT) levels^[1].

References:
[1]. Taku Fukuzawa, et al. Long lasting neutralization of C5 by SKY59, a novel recycling antibody, is a potential therapy for complement-mediated diseases. Sci Rep. 2017 Apr 24;7(1):1080.
[2]. Wioleta M Zelek, et al. Characterizing a pH-switch anti-C5 antibody as a tool for human and mouse complement C5 purification and cross-species inhibition of classical and reactive lysis. Immunology. 2018 Nov;155(3):396-403.