Recently, the clinical phase II study of LW402, a novel oral highly JAK1-selective inhibitor developed by LWBP, for the treatment of autoimmune diseases such as atopic dermatitis(AD) and rheumatoid arthritis(RA), was successfully initiated and patients were enrolled. The results of the clinical phase I study show that LW402 is a potentially safer and more efficient JAK1 selective inhibitor that inhibits cytokine signalling and suppresses autoimmune disease-associated inflammation by blocking the JAK-STAT signalling pathway, which can effectively control the progression of autoimmune diseases and is expected to be an important strategy for the treatment of autoimmune diseases.
Autoimmune diseases are a class of inflammatory immune diseases marked by abnormal topical and/or systemic inflammatory immune responses. About 5-8% of the world's population is threatened by autoimmune diseases, and the increasing disability and mortality rates reflect the enormous challenges in the diagnosis and treatment of autoimmune diseases. Over 100 autoimmune diseases have been identified, including rheumatoid arthritis (RA), ankylosing spondylitis (AS), juvenile idipathic arthritis (JIA), non-radiographic Axial Spondyloarthritis (nr-AxSpA), psoriasis, psoriatic arthritis (PsA), Crohn's disease (CD), ulcerative colitis (UC), systemic lupus erythematosus (SLE), lupus nephritis (LN), multiple sclerosis (MS), and bronchial asthma. The autoimmune and inflammatory drugs market is ranked No. 2 among the Top 100 drugs in terms of global sales in 2020.
The family of JAK kinases has been a popular target in recent years and several products have been approved worldwide. The first generation of JAK inhibitors targeting multiple JAK family members have shown significant efficacy in inflammatory and oncological indications, and have demonstrated superior efficacy and safety to Methotrexate（MTX）. However, as the JAK family mediates the signalling of multiple cytokines, inhibition of multiple JAK family members increases the risk of thrombosis and tumour. Second generation JAK inhibitors work on specific targets related to the disease signalling pathway while leaving other cytokine-mediated pathways unaffected, thereby reducing side effects. The development of a new generation of JAK1-selective inhibitor with improved efficacy and safety is an unmet clinical need, and there is an urgent need to address the safety and tolerability aspects of JAK inhibitors, which, if successfully developed, could lead to a new generation of therapy.
LW402 is a new generation of oral JAK1-selective inhibitor developed independently by LWBP. It has demonstrated excellent selective inhibition rate of JAK1 in clinical phase I study and no side effects such as infectious diseases and thrombophilia were found as in other drugs. LWBP will fast-track the multi-centre clinical phase II study of LW402 and complete the commercialisation process rapidly in order to bring LW402 to market as soon as possible. This will help LWBP to gain a foothold in the field of autoimmune diseases and provide better treatment options to improve the quality of life for patients.