Encouraging Preclinical Results Generated with Sareum’s TYK2/JAK1 Inhibitors in a Disease Model of Lupus
Sareum Holdings plc (AIM: SAR), the specialist drug development company delivering targeted small molecule therapeutics to improve the treatment of cancer and autoimmune diseases, is pleased to announce that encouraging results have been published for its small molecule dual tyrosine kinase 2 (TYK2) and Janus kinase 1 (JAK1) inhibitors in disease model studies of systemic lupus erythematosus (SLE) by its collaborator, SRI International.
These studies were supported by a research grant from the US Department of Defense (DoD) and the report was recently published on the website of the Defense Technical Information Center (https://apps.dtic.mil/sti/citations/AD1087498).
The authors concluded that an approach using selective TYK2/JAK1 inhibitors may lead to the development of a therapy for lupus that does not involve the harmful side effects of systemic immune system suppression and may benefit numerous lupus patients in need of new options. They also noted that the results could influence treatments of other autoimmune diseases such as arthritis and psoriasis.
Specifically, it was reported that treatment with TYK2/JAK1 inhibitor SAR-20351 (now known as SDC-1802) reduces autoantibodies (biological markers of lupus severity) in a spontaneous mouse model of SLE. The data also provided evidence that SAR-20351 inhibits cytokines that play a critical role in lupus, including interferon-alpha, IL-6 and IL-23. The inhibition of IL-23 signalling by SAR-20351 may play a role in the decrease of autoantibodies in the lupus mouse model, as IL-23 signalling drives the differentiation of Th17 cells, which leads to autoantibody production and are pathogenic in lupus.
SAR-20351/SDC-1802 has been selected as a preclinical development candidate targeting cancer based on its overall profile that includes supportive data recently presented in October 2019 at the AACR-NCI-EORTC International Cancer Conference. Sareum is advancing a different TYK2/JAK1 inhibitor – SDC-1801 – as a preclinical candidate targeting autoimmune diseases.
Dr Tim Mitchell, CEO of Sareum, commented :
“These data from studies using our small molecule TYK2/JAK1 inhibitors add to the body of evidence supporting this novel mechanism of action as a promising approach to treating autoimmune diseases such as SLE. Our own studies have also confirmed this potential in autoimmune diseases such as psoriasis and rheumatoid arthritis and we are delighted that this work indicates a possible application in lupus, which remains a condition with high unmet medical need. This approach has also been recognised more broadly in the industry with several molecules targeting this pathway advancing through development. We look forward to reporting further progress as we advance our TYK2/JAK1 candidates through preclinical development.”
Sareum entered into a co-development agreement with SRI International (Menlo Park, CA, USA) in April 2013 to develop TYK2 inhibitors in autoimmune diseases. Sareum retains commercialisation rights for these and other TYK2 inhibitors with profiles optimised for oncology indications.
Lupus is an autoimmune disease in which the body’s immune system attacks healthy tissue in many parts of the body. Common symptoms include painful and swollen joints, fever, chest pain, hair loss, mouth ulcers, swollen lymph nodes, feeling tired and a red rash, which is most commonly on the face. Lupus significantly increases the risk of cardiovascular disease with this being the most common cause of death. The Lupus Foundation of America estimates that at least five million people worldwide have a form of lupus, with systemic lupus erythematosus (SLE) accounting for 70% of all cases. The rate of SLE in developed countries ranges from 20 to 70 per 100,000. Women between the ages of 15 and 45 are affected about nine times more often than men.*
* Sources – The Lupus Foundation of America, Wikipedia
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