Background: The complement system usually helps protect against microbial infection, but
it could also be involved in the onset of various diseases. Inhibition of complement component 5 (C5)
with eculizumab has resulted in a significant reduction of hemolysis, reduction of thromboembolic
events, and increased survival in patients with Paroxysmal Nocturnal Hemoglobinuria (PNH). However,
eculizumab requires frequent intravenous infusions due to the abundance of C5 in plasma and
some patients may still experience breakthrough hemolysis. This review introduces the recent body of
knowledge on recycling technology and discusses the likely therapeutic benefits of SKY59, a novel
recycling antibody, for PNH and complement-mediated disorders.
Methods: By using recycling technology, we created a novel anti-C5 antibody, SKY59, capable of
binding to C5 pH-dependently.
Results: In cynomolgus monkeys, SKY59 robustly inhibited C5 and complement activity for significantly
longer than a conventional antibody. SKY59 also showed an inhibitory effect on C5 variant
p.Arg885His, whereas eculizumab does not suppress complement activity in patients with this type of
Conclusion: SKY59 is a promising anti-C5 biologic agent that has significant advantages over current
therapies such as long duration of action and efficacy against C5 variants.