Fig. 4

Preclinical and clinical trials of complement therapy. Complement therapy progresses through different stages, spanning from preclinical work to market authorization. These stages include laboratory research, animal models, clinical phases I, II, and III, and final clinical implementation. The therapeutic goals are categorized into four quadrants, representing major complement categories: anaphylatoxins, active pathways, amplification and terminal pathways, and effectors. Each arrow denotes a specific agent and its development stage. Drugs targeting C1r/s and MASP include Cinryze (Shire), Berinert (CSL Behring), Cetor (Sanquin), and Ruconest (Pharming), which are already being used in clinics; drugs targeting C1q include ANX005 (Annexon); drugs targeting C1s include TNT003 (True North), TNT009 (True North), and BIVV020 (Sanofi); TP10 (CDX-1135; Celldex Therapeutics) targets the soluble form of complement receptor type 1 (CR1); OMS721 (Narsoplimab, Omeros) targets the MASP-2 target; Drugs targeting MASP-3 include OMS906 (Omeros); drugs targeting Properdin include CLG561 (Novartis) and NM9401 (Novelmed); drugs targeting C3 include AMY-101 (Amyndas), APL-1 (Apellis), APL-2 (Apellis), CB2782 (Catalyst), Cp40 (Amyndas); drugs targeting C3b and convertases include AMY-201 (Amyndas), and Mirococept (MRC); drugs targeting FB include Bikaciomab (Novelmed); drugs targeting FD include Lampalizumab (Genentech), ACH-4471 (Achillion), and “Compound 6”(Novartis); drugs targeting C5 include Eculizumab (Soliris, Alexion), ALXN1210 (Alexion), ALXN5500 (Alexion), LFG316 (Novartis), Coversin (Akari), RA101495 (Ra Pharma), ALN-CC5 (Alnylam), RA101348 (RaPharma), ARC 1905 (Zimura; Ophthotech), and the affibody SOBI002 (Swedish, Orphan Biovitrum) targets C5 (programme recently terminated); drugs targeting C5a include IFX-1 (InflaRx), ALXN-1007 (Alexion), NOX-D21 (Noxxon Pharma); drugs targeting C5aR include CCX168 (Chemocentryx); C6 target drug includes Regenemab (Regenesance); CR2–FH target drug includes TT30 (ALXN 1102; Alexion)