TYK2/JAK1 - Covid-19

Diseases such as Covid-19, SARS, MERS, influenza etc. can be fatal due to a "cytokine storm" overreaction of the immune system leading to acute respiratory distress syndrome (ARDS).

Key cytokines elevated in Covid-19 intensive care unit patients are reported to include: IL-2, IL-6, IL-7, IL-10, TNFa – all of which signal via JAK-family kinases.

Clinical trials of JAK-family inhibitors ruxolitinib, tofacitinib, baricitinib, TD-0903 in Covid-19 patients are in progress or planned.

Viral induced secondary bacterial infections induce IL-1β and GM-CSF3, and GM-CSF administration reported to improve outcome in patients with pneumonia-associated ARDS. This IL-1β - GM-CSF pathway is blocked by virally-induced IFNα and IFNγ.

JAK inhibition can block IFNα/γ signalling and thus restores GM-CSF levels. However, GM-CSF signals via JAK2, indicating that a JAK2 inhibitor is likely to counter the beneficial effects of GM-CSF level restoration. This suggests a JAK inhibitor that inhibits JAKs other than JAK2 would be optimally beneficial, and Sareum's SDC-1801 fits this profile, inhibiting TYK2 and JAK1, but not JAK2.

Whilst developing SDC-1801, we have produced compelling cellular and in-vivo data in models of autoimmune disease to demonstrate the beneficial effects of SDC-1801 in modulating the key cytokines involved in the cytokine storm phase of Covid-19.

Sareum has been conditionally awarded a grant of approximately £174,000 by UK Research & Innovation (“UKRI”) to investigate the therapeutic potential of SDC-1801 in preclinical models of severe phase Covid-19.

Further details can be made available to potential funding, collaboration and/or licensing partners on request.

Glossary:

IFN - Interferon; G-CSF – Granulocyte Colony Stimulating Factor ; GM-CSF – Granular Macrophage Colony Stimulating Factor

References:                                                                                       

Huang et al Lancet 2020; 395:497-506
Berg et al Eur Respir J 2017; 50:160193
Herold et al Am J Respir & Criti Care Med 2015; 189(5):609-11

 

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