ART26.12, A NOVEL FATTY ACID BINDING PROTEIN 5 (FABP5) INHIBITOR, SHOWS EFFICACY IN PRECLINICAL MODELS OF PSORIASIS

Fatty acid-binding protein 5 (FABP5) is upregulated in psoriasis. This study assessed the efficacy of the potent, selective, and orally active FABP5 inhibitor ART26.12 in preclinical psoriasis models. ART26.12 (25 or 100 mg/kg BID) or BMS-986165 (TYK2 inhibitor; 10 mg/kg QD) were given orally for 10 days in the imiquimod mouse model. Imiquimod increased psoriasis-like symptoms. ART26.12 (25 mg/kg BID) and BMS-986165 comparably reduced psoriasis-like symptoms by Day 6 of IMQ treatment. Histopathology showed that ART26.12 reduced symptom severity, e.g., hyperkeratosis, parakeratosis, epidermal acanthosis, and inflammatory infiltrates. Proteomic analysis indicated ART26.12 rescued expression of fillagrin-2, promoted epidermal differentiation complex associated proteins and modulated PPAR, NF-kB, and PKC pathways likely downstream of lipid modulation. Lipidomic analysis showed widespread modulation including ceramides and linoleic acid derivatives. These data suggest ART26.12 may be a potential psoriasis treatment