Complement C1s + Factor Bb

Class

AAV gene therapy encoding two antibody fragments for dual classical/alternative complement-pathway suppression

Complement is part of the innate immune system, a network of blood proteins that detect pathogens or damaged tissue and trigger inflammation, opsonization (marking targets for immune clearance), and direct cell lysis. Two entry routes feed into this cascade: the classical pathway, initiated when antibodies or certain proteins bind a target and activate the C1 complex (of which C1s is the enzymatic component), and the alternative pathway, which is continuously active at low levels and amplifies through a fragment called Bb combining with C3b to form a convertase. Both routes converge on generating C3 convertases that cleave C3, driving inflammation and tissue injury. In diseases where complement is chronically or inappropriately activated, such as inflammatory eye disease, kidney disease, or certain neurologic and hematologic disorders, excessive signaling through either or both pathways contributes to damage. Blocking a single enzyme sometimes fails because the other pathway compensates; targeting both C1s and Bb aims to suppress classical and alternative activation simultaneously without shutting down complement's lectin pathway or terminal membrane-attack complex entirely. Delivering this as an AAV gene therapy encoding antibody fragments is intended to produce sustained local inhibition from a single administration, rather than relying on repeated injections of separate biologic drugs.