APL-2 and complement inhibition; a potential treatment of PNH and other complement complement-mediated diseases
Carolina Vega
Director of Pharmaceutical Development, Apellis Pharmaceuticals
The complement system is part of the body’s immune system. It can be activated by three principal activation pathways: the classical pathway, the lectin pathway and the alternative pathway. All three activation pathways converge on C3, leading to three principal effects of complement activation: opsonization, inflammation and the membrane attack complex formation. Under conditions of excessive or uncontrolled activation, the complement system plays a key role in a wide range of autoimmune and inflammatory diseases. Apellis lead product candidate, APL-2, targets the complement system at the C3 level, inhibiting all effects of the complement cascade. By inhibiting C3, we believe that APL-2 may effect disease control and disease modification.
APL-2 is the conjugate of APL-1, a synthetic cyclic peptide, with a long half-life. It is currently in the clinic for the treatment of PNH and AMD. Recent data from healthy volunteer studies confirmed that pharmacological doses of APL-2 were safe and well tolerated and that APL-2’s PK/PD profile supports daily SC administration. In addition, daily APL-2 doses of 180 mg and 270 mg significantly reduced hemolytic activity as early as eight days after the start of dosing, and this inhibition was maintained through the dosing period.