FLX193: A Potent, Selective CCR4 Antagonist for Allergic Disorders

Abstract Type 2 helper T cells (Th2)cells have been shown to express CCR4 receptor, and play a critical role in driving the pathogenesis of asthma and atopic dermatitis. FLX193 is a best-in-class, highly-potent and selective small molecule CCR4 antagonist under investigation for the treatment of allergic disorders. FLX193 blocked migration of CCR4+ Th2 cells (human and mouse) towards CCL17 and CCL22 in an in vitro chemotaxis assay. FLX193 is well-tolerated in animals at efficacious doses. In an Ovalbumin (OVA)-induced asthma model, FLX193 significantly reduced lymphocyte and eosinophil counts in the Bronchoalveolar lavage (BAL) fluid and showed a reduction of the effector Th2-relevant cytokines IL-5 and IL-13. FLX193 treatment also reduced the levels of CCL17 and CCL22 in the BAL fluid, indicating an overall reduction of inflammation. In addition, we used an atopic dermatitis mouse model to demonstrate that treatment with FLX193 decreased CCR4+ T-cell mediated inflammation. Hence, FLX193 shows promise in the treatment of atopic dermatitis.