Nanofitins^® as alternative scaffold for complement pathway inhibition

Nanofitins^® efficiently inhibit complement pathway by targeting C3/C3b

Affilogic discovery process was engaged to identify Nanofitins targeting C3/C3b and mimicking compstatin pharmacology, and this therapeutic, namely APL-1030, is developped in collaboration with Apellis, . APL-1030 is thermostable, binds C3 (KD, 1.59 nM) and C3b (KD, 1.11 nM), and inhibits complement activation via classical (IC50 = 110.8 nM) and alternative (IC50 = 291.3 nM) pathways in Wieslab assays. C3b-binding sites of APL-1030 and compstatin were shown to overlap by X-ray crystallography of C3b-bound APL-1030. The proof of concept of inhibition of different complement pathways has been demonstrated in rodents and non-human-primate (NHP) models. Thanks to the Nanofitin scaffold, APL-1030 properties enable bifunctional moieties, gene therapy, and tissue-targeted C3 pharmacologics for diseases with high unmet need. (Garlich et al., Discovery of APL-1030, a Novel, High-Affinity Nanofitin Inhibitor of C3-Mediated Complement Activation, Biomolecules 2022)