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[1][2].

Research Areas >> Cardiovascular Disease

Signaling Pathways >> Immunology/Inflammation >> Complement System

Research Areas >> Metabolic Disease

Crovalimab (SKY59; RO7112689; 0-100 μg/mL) 抑制经典途径和反应性裂解系统中的溶血[2]。

Crovalimab (SKY59; RO7112689; 20 mg/kg; 静脉注射; 仅第 0 天一次) 完全防止食蟹猴体内血浆 C5 的积累。Crovalimab-IgG1 (SG115) 显示出较慢的清除率：1.87mL/day/kg[1]。 Crovalimab (20 mg/kg; 静脉注射; 单剂量) 稳定抑制血浆中的补体活性 8 周[1]。 Crovalimab (第 0 天静脉注射 5mg/kg; 第 7、21、35、49 和 63 天皮下注射 2mg/kg) 在 cRBC 裂解试验中导致超过 20% 的血清溶血活性，吞咽困难和乳酸脱氢酶 (LDH) 和丙氨酸转氨酶 (ALT) 水平急剧升高[1]。

[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.