Autoimmune - TYK2/JAK1 kinases

The TYK/JAK cell signalling family (TYK2, JAK1, JAK2, JAK3) is important for maintaining a healthy immune system. TYK2 and JAK1 are involved in a signalling pathway that is deregulated in multiple autoimmune diseases, notably psoriasis

Members of the JAK family are the targets of several marketed and clinical-stage drugs for cancer and autoimmune diseases, although there are currently no marketed products specifically targeting TYK2. In clinical trials, there has been strong clinical validation (from BMS and Pfizer) for TYK2 and TYK2/JAK1 in psoriasis and psoriatic arthritis. These companies are also undertaking mid-stage clinical trials of TYK2 and TYK2/JAK1 inhibitors for lupus, ulcerative colitis, Crohn’s disease, vitiligo and other autoimmune diseases.

Sareum's TYK2/JAK1 preclinical devlopment candidate molecule, SDC-1801, demonstrates high selectivity for TYK2 and JAK1 kinases (particularly over related JAK2 and JAK3), compelling activity in disease models of psoriasis and rheumatoid arthritis, the potential for once-daily oral dosing and a good early safety profile. Closely related molecules, including SAR-20347, also show good activity in models of inflammatory bowel disease and systemic lupus erythematosus (lupus). These attributes have supported the progression of SDC-1801 through preclinical development and, pending regulatory approval, advancement into human clinical trials.

Preclinical development candidate SDC-1801 was nominated from a novel series of compounds designed and identified by Sareum following a rigorous selection process. The company is also completing its assessment of further dual TYK2/JAK1 inhibitors for the potential treatment of certain cancers and/or as a back-up to SDC-1801.

The JAK cell signalling family (TYK2, JAK1, JAK2, JAK3) is an area of growing commercial focus. There is strong clinical validation (BMS, Pfizer) for TYK2 and TYK2/JAK1 in psoriasis and psoriatic arthritis. Additionally, there is strong scientific evidence for the roles of TYK2/JAK1 role in modulating the severe inflammatory responses and respiratory symptoms arising from coronavirus and other viral infections. Several JAK family inhibitors have been approved or are in clinical trials for use against Covid-19.

Further information on Sareum's TYK2/JAK1 Covid-19 research programme can he found here.

Selection of TYK2/JAK1 for autoimmune diseases

Sareum/SRI Journal of Immunology paper: Inhibition of TYK2 and JAK1 Ameliorates Imiquimod-Induced Psoriasis-like Dermatitis by Inhibiting IL-22 and the IL-23/IL-17 Axis.