Definition

A humanized monoclonal antibody directed against complement factor Bb (FBb; Bb) that can be used to treat various alternate pathway (AP)-mediated diseases. Upon administration, anti-factor Bb monoclonal antibody NM8074 selectively targets, binds to and neutralizes Bb. This prevents the binding of Bb to C3 and prevents the formation of protease C3 convertase (C3Bb). This prevents the conversion of C3 into the fragments C3a and C3b, thereby preventing C3b deposition and C3b-mediated extravascular hemolysis. Also, by preventing the formation of C3Bb, C3Bb is unable to bind to C3b to form the protease C5 convertase (C3BbC3b). As C5 convertase is responsible for the conversion of C5 to C5a/C5b and initiation of membrane attack complex (MAC), NM8074 is able to prevent MAC-mediated tissue damage. Altogether, NM8074 inhibits the activation of the alternative complement pathway (ACP). Overactivation of AP plays a key role in the initiation and propagation of C3b deposition, inflammation and tissue destruction. Bb is created when complement factor D, a serine protease, cleaves complement factor B into 2 fragments, Ba and Bb, in the AP of the complement cascade. NM8074 does not block the classical pathway (CP) which is critical for host defense against infections.