Discovery of cellular mechanism of action of tACPA in rheumatoid arthritis

ModiQuest, a Dutch antibody drug development and diagnostics company focused on chronic inflammatory diseases, has discovered the cellular mechanism of action of its therapeutic anti-citrullinated protein lead antibodies (tACPA) for the treatment of rheumatoid arthritis (RA) and other diseases.

To accelerate tACPA development towards clinical Proof of Concept, facilitate funding, and attract a development partner, Citryll B.V. was founded as a single asset drug development company.

tACPAs inhibit the formation of neutrophil extracellular traps

The tACPAs are active in different validated RA animal models and models for other human diseases. They exert their therapeutic effect by inhibiting the formation of Neutrophil extracellular traps (NETs) as shown with primary human neutrophils. NETs are extracellular lattices of decondensed chromatin decorated with antimicrobial factors, whose function is to eliminate invading microorganisms. Dysregulated NETosis constitutes a pathogenic mechanism in autoimmune and sterile inflammatory diseases. This offers novel therapeutic opportunities for diseases with unmet medical needs, including RA, where existing treatments can have serious side-effects and comprise a significant percentage of non-responders. NETosis is peptidyl arginine deiminase (PAD) dependent, creating neo-epitopes that trigger autoimmunity and breaking of tolerance in RA.

ModiQuest has discovered tACPAs using its proprietary antibody generation technology platforms ModiFuse™ (highly efficient hybridoma electrofusion technology), ModiSelect™ (B cell selection technology for low immunogenic or multiple antigen targets) and ModiPhage™ (proprietary phage display libraries). All three technology platforms are also used by ModiQuest’s service business, ModiQuest Research B.V., for custom antibody lead generation in third party service projects with a recent addition of an innovative platform for difficult antibody drug targets, ModiVacc™.