Investigating the therapeutic potential of TYK2 / JAK1 inhibitor SDC-1801 in severe phase Covid-19

Sareum正在开发SDC-1801，一种TYK2和JAK1酶的小分子抑制剂，作为一种潜在的治疗各种炎症性疾病的药物，如牛皮癣、狼疮和克罗恩病。细胞之间使用细胞因子相互传递信号，SDC-1801的工作原理是阻断特定的细胞因子信号通路，从而减少炎症。Covid-19是由SARS-CoV-2病毒引起的，通常会导致轻微的疾病自行解决。然而，一些患者会患上一种潜在的致命的严重疾病，原因是免疫系统的“细胞因子风暴”引起的炎症，导致急性呼吸窘迫综合征(ARDS)，需要重症监护。在重症新冠肺炎患者中，一种主要的炎症途径被过度激活，称为干扰素1型，被SDC-1801阻断。因此，我们相信SDC-1801可以通过阻断干扰素1型信号和减少细胞因子风暴期间的炎症而使重症新冠肺炎患者受益。此外，抑制TYK2已经被证明可以减少流感患者的细菌性肺炎。我们相信SDC-1801将在新冠肺炎患者中起到同样的作用，潜在地降低高达50%的新冠肺炎患者的细菌感染水平。本研究的目的是研究SDC-1801在人类细胞感染SARS-CoV-2后对细胞因子信号的影响，以确保在这种疾病中能够阻断干扰素1型途径。我们还将使用小鼠模型来研究SDC-1801是否可以减少SARS-CoV-2感染后的细菌性肺炎。如果这项研究成功，我们的目标是在2021年开始对重症新冠肺炎患者进行SDC-1801的临床试验。

Sareum is developing SDC-1801, a small-molecule inhibitor of kinases TYK2 and JAK1, as a potential therapeutic for a wide range of inflammatory diseases such as psoriasis, lupus and Crohn's disease. Cells signal to each other using cytokines, and SDC-1801 works by blocking specific cytokine signalling pathways, leading to reduced inflammation.Covid-19 is caused by the virus SARS-CoV-2, and usually results in a mild disease that resolves on its own. However, some patients develop a potentially fatal severe disease due to inflammation arising from a 'cytokine storm' overreaction of the immune system leading to Acute Respiratory Distress Syndrome (ARDS), requiring intensive care. A major inflammatory pathway over activated in severe Covid-19 patients, known as Interferon Type 1, is blocked by SDC-1801\. We believe that SDC-1801 could therefore benefit severe phase Covid-19 patients by blocking Interferon Type 1 signals and reducing the inflammation during 'cytokine storm'.Furthermore, inhibiting the kinase TYK2 has been shown to reduce bacterial pneumonia in influenza patients. We believe SDC-1801 will have the same effect in Covid-19 patients, potentially reducing the levels of bacterial infection that have been seen in up to 50% of Covid-19 patients.The aim of this research is to investigate the effects of SDC-1801 on cytokine signalling after human cells are infected with SARS-CoV-2 to ensure that the Interferon Type 1 pathway can be blocked in this disease. We will also use mouse models to investigate whether SDC-1801 can reduce bacterial pneumonia after SARS-CoV-2 infection. If this research is successful, we would aim to begin a clinical trial of SDC-1801 in severe-phase Covid-19 patients during 2021\.