The complement cascade plays a pivotal role in both innate and adaptive immune systems. It is responsible for recognizing and eliminating pathogens and damaged cells.
Complement proteins are produced primarily by the liver and circulate in the blood and through the body’s tissues. The complement cascade may be activated through three principal pathways, known as the classical, lectin, and alternative pathways, all of which converge at C3. The C3 protein enables three principal immune responses: opsonization, inflammation and formation of the membrane attack complex. When C3 is activated, C3 fragments, such as C3b, tag cell surfaces in a process called opsonization, which marks the cells for removal from tissues or the bloodstream. Two other fragments, C3a and C5a, are released, contributing to inflammation in the surrounding tissues. Further complement activation causes membrane attack complex formation on cell surfaces, piercing holes and causing cells to lyse, or rupture.
Under conditions of excessive or uncontrolled activation, the complement cascade is believed to play a key role in the onset and progression of a broad range of serious diseases. In these diseases, the complement cascade acts directly through tissue destruction by the membrane attack complex and indirectly by signaling other elements of the immune system to inappropriately target otherwise healthy tissues. Because the contribution of complement activation to the development and progression of these diseases is not fully understood, it has been difficult to develop therapeutics that ameliorate the conditions contributing to these diseases by targeting only one of the complement activation pathways.
We have designed pegcetacoplan (APL-2) to target complement proteins centrally at the level of C3. We believe that this approach can regulate uncontrolled or excessive complement activation that occurs in several debilitating diseases, including those within hematology, ophthalmology, and nephrology. We believe that pegcetacoplan has the potential to be a best-in-class and first-in-class treatment that may address the limitations of existing treatment options or provide a treatment option where today there is none.