CVXL-0074 is a small molecule inhibitor targeting both SYK and JAK3 for the oral treatment of diseases with a immune-dedicated inflammatory disease such as rheumatoid arthritis, atopic dermatitis, allergic conjunctivitis and possibly DLBCL. The compound demonstrated an efficacy in a preclinical arthritis model and in a canine model of atopic dermatitis.
The kinases SYK and JAK3 are at the core of immune signaling. SYK is regulating BCR-dependent signaling, therefore a SYK inhibitor is expected to limit B cell proliferation and auto-antibody production. JAK3 is involved in cytokine signaling, and a JAK3 inhibitor is expected to reduce inflammation. The inhibition of these two key signaling pathways may result in a greater clinical benefit. Furthermore, a selective SYK and JAK3 expected to improve the safety profile reducing systemic adverse effects (vs the non SYK selective fostamatinib) and avoiding the JAK-2 related anemia and the LDL increase (vs the pan-JAK inhibitor tofacitinib).