On March 23th, 2020, Shenzhen Chipscreen Biosciences Co., Ltd. (Chipscreen Biosciences, Stock Symbol: 688321.SH) announced that the company’s application for Investigational New Drug (IND) of CS12192 has been accepted by Center for Drug Evaluation, National Medical Products Administration of China (Application No.: CXHL2000118, CXHL2000119). CS12192 is a new chemical entity with novel mechanism of actions discovered and developed by Chipscreen Biosciences for the treatment of autoimmune diseases (AD) and other related diseases like graft versus host diseases (GVHD).

Autoimmune diseases include a group of diseases that express with continuous damage to a variety of tissues and organs due to the abnormal immune response against self-antigens, pathogens or other environmental factors. As one of the most common chronic diseases, over 100 types of autoimmune diseases have been identified such as rheumatoid arthritis and psoriasis etc. The prevalence of autoimmune diseases is around 3% to 5% of total population worldwide. Autoimmune diseases are highly heterogeneous in pathogenesis with largely unknown, and have high rates of recurrence and disability. Currently, there are needs for long-term efficient and safe clinical treatment for autoimmune diseases, showing an obvious gap in unmet clinical need. In addition, the over-activated immune cells in some acute and chronic infectious diseases and/or allogenic organ transplantation may cause uncontrolled tissue inflammatory damage and could sometimes be life-threatening. For these kinds of autoimmune-related diseases, there still lacks effective targeted intervention drugs.

Previous research showed that the elevated level of multiple cytokines and activation of JAK signaling pathways are common in all autoimmune diseases. Janus kinases (JAK) are a family of cytokine receptor-associated tyrosine kinases that mediate the intracellular signaling upon immune cytokine stimulation. JAK family consists of four subtypes such as JAK1, JAK2, JAK3 and Tyk2, mediating intercellular signaling of various immune cytokines as well as down streaming biological activities, which is strongly related to immune system regulation. Therefore, inhibitors targeting JAK family has become a new strategy in drug development against autoimmune diseases. At present, there are four JAK kinase inhibitors that inhibit all three JAK subtypes approved for different autoimmune diseases such as rheumatoid arthritis and psoriasis, etc. There is no approval yet of selective JAK3 inhibitor so far. Although these pan-JAK inhibitor drugs have shown certain clinical benefits, obvious limitations in safety and some undesired side effects restrain their clinical applications.

CS12192 is a selective JAK3 inhibitor discovered by Chipscreen Biosciences and protected with global intellectual property, also partially inhibits JAK1 and TBK1 kinases. TBK1 also plays a key role in the induction of interferon signaling during inflammation, which may cause excessive tissue damage. No TBK1 inhibitor has been currently approved. In preclinical evaluation, CS12192 showed significant efficacy in multiple autoimmune disease models in preclinical studies, such as rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, and GVHD. Particularly, it showed encouraging therapeutic effects in some autoimmune disease models which clearly differentiate from the existing JAK inhibitors. Further, CS12192 showed a good safety profile with not only effectively inhibiting the immune over activation-mediated inflammation, but also reducing the tissue invasion by immune cells through TBK1 inhibition. CS12192 is expecting with better efficacy and safety profile over comparators via its target selectivity and may add a new treatment option for the clinical treatment of autoimmune diseases and autoimmunity-related diseases.

Chipscreen Biosciences has applied for almost 20 patents with CS12192. Also, the discovery and development of CS12192 has been partially supported by a number of national, provincial and municipal research grands in China.