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

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\.