TYK2 is an intracellular tyrosine kinase protein that mediates immune signaling pathways involved in both innate and adaptive immunity. TYK2 and the cytokines that signal through it participate in inflammatory cascades that can be dysregulated in disease. Therapeutic inhibition of TYK2 and associated cytokine pathways has been broadly validated as a therapeutic approach to address immune dysfunction to treat immune mediated diseases.
The Role of TYK2 in Immune-Mediated Diseases
TYK2 as a target has a significant effect on the IL12/23 pathway and on the interferon pathway. Both pathways are involved in a number of immune-mediated diseases. At Alumis, we also conducted extensive genomic analysis to see how TYK2 is related to multiple diseases and found approximately 20 diseases so far that are affected by TYK2 including psoriasis, lupus (SLE), psoriatic arthritis, rheumatoid arthritis, Crohn’s disease and ulcerative colitis.
We believe that TYK2 plays a role in many of these diseases and that the opportunity to help patients is significant. Genetic studies have identified a naturally-occurring loss of function mutation in the TYK2 gene (in 3-5% of the human population) that appears to be protective against an array of autoimmune or immune-mediated disorders. In other words, for these people, TYK2 function is naturally absent or "inhibited" and this correlates with a reduced risk of developing immune-mediated/autoimmune diseases. These data validate the role of TYK2 in immune-mediated diseases and of TYK2 inhibition as a therapeutic target for patients with these diseases. Given the benign safety and tolerability profile of TYK2 inhibition, we believe TYK2 inhibitors will be fundamental combination partners for multiple treatments moving forward.