**Background**
The complement system is a critical component of the innate immune response, playing a vital role in pathogen elimination and the inflammatory process. However, abnormal activation of the terminal complement pathway can lead to excessive inflammatory damage and tissue injury. Complement protein C5 is a central regulator in this process; its cleavage into C5a and C5b triggers the formation of the membrane attack complex (MAC), which can cause cell lysis and organ damage. This mechanism is heavily implicated in the pathogenesis of various autoimmune and kidney diseases, including IgA nephropathy, lupus nephritis, and myasthenia gravis. Consequently, targeting C5 to block the terminal pathway has become a significant therapeutic strategy. In this context, we will introduce a high-affinity antibody inhibitor – Gefurulimab.
**Definition**
Gefurulimab (ALXN-1720) is a bispecific VHH antibody inhibitor that targets complement protein C5 and serum albumin (HSA). According to the Gefurulimab description, it specifically binds to C5 to inhibit its cleavage into C5a and C5b, thereby blocking the activation of the terminal complement pathway.
**In Vitro Studies**
The Gefurulimab biological activity is characterized by its high affinity and specificity. In vitro studies demonstrate that Gefurulimab binds specifically to human and cynomolgus monkey C5, as well as serum albumin. A key feature of its binding profile is that its affinity for C5 exhibits pH-dependent changes, whereas its affinity for HSA remains relatively stable regardless of pH. Furthermore, the molecule is capable of binding hC5 and HSA simultaneously, a design intended to optimize its pharmacokinetic properties for low-volume subcutaneous administration. By reducing the formation of the membrane attack complex (MAC), Gefurulimab effectively mitigates inflammatory damage. For researchers seeking detailed Gefurulimab technical information, this VH-VH’ format antibody is suitable for applications such as ELISA, FACS, and functional assays. In conclusion, Gefurulimab is a high-affinity bispecific VHH antibody that effectively inhibits C5 activation to treat complement-mediated diseases.
Keywords
Gefurulimab, 2456407-94-4, ALXN-1720, ALXN1720, ALXN 1720, Complement System, bispecific antibody, complement, C5, albumin, Inhibitor, inhibitor, inhibit
References
[1] Sandra Rayego-Mateos, et al. Targeting inflammation to treat diabetic kidney disease: the road to 2030. Kidney Int. 2022 Dec 5:S0085-2538(22)01017-1.
[2] Mullin M, et al. Applications and challenges in designing VHH-based bispecific antibodies: leveraging machine learning solutions. MAbs. 2024 Jan-Dec;16(1):2341443.
[3] Miwa T, et al. Expansion of Anticomplement Therapy Indications from Rare Genetic Disorders to Common Kidney Diseases. Annu Rev Med. 2024 Jan 29;75:189-204.
[4] Jindal S, et al. Characterization of the bispecific VHH antibody gefurulimab (ALXN1720) targeting complement component 5, and designed for low volume subcutaneous administration. Mol Immunol. 2024;165:29-41.