SKY59, A Novel Recycling Antibody for Complement-mediated Diseases

Area of Science:

• Immunology
• Pharmacology

Background:

• The complement system plays a dual role in host defense and disease pathogenesis.
• Eculizumab effectively treats Paroxysmal Nocturnal Hemoglobinuria (PNH) by inhibiting complement component 5 (C5), but limitations include frequent infusions and breakthrough hemolysis.
• Some patients with PNH exhibit C5 mutations rendering them resistant to eculizumab.

Purpose of the Study:

• To introduce recycling technology for developing novel complement inhibitors.
• To evaluate the therapeutic potential of SKY59, a novel recycling anti-C5 antibody, for PNH and other complement-mediated disorders.

Main Methods:

• Development of SKY59, a novel anti-C5 antibody utilizing recycling technology with pH-dependent C5 binding.
• Assessment of SKY59's inhibitory effects and duration of action in cynomolgus monkey models.

Main Results:

• SKY59 demonstrated prolonged inhibition of C5 and complement activity in cynomolgus monkeys compared to conventional antibodies.
• SKY59 effectively inhibited the C5 p.Arg885His variant, unlike eculizumab, indicating efficacy in a subset of patients resistant to current therapy.

Conclusions:

• SKY59 represents a promising biologic agent for C5 inhibition with a longer duration of action.
• SKY59 exhibits significant advantages over existing therapies, including efficacy against C5 variants, offering new therapeutic possibilities for PNH and complement-mediated diseases.