NYSKAPNING-NYSKAPNING

The innovation project identified a new drug target for small molecule inhibitors, drugs that inhibit the kinase LTK for the treatment of autoimmune diseases such as immune thrombocytopenia (ITP). Autoimmune diseases are characterized by patients having plasma cells that secrete autoantibodies causing tissue damage. In ITP, patients often have autoantibodies that bind to and destroy platelets. ITP patients with low platelet counts risk developing fatal bleeding. We found that the drug target, LTK, is important for the function and survival of plasma cells, LTK allows cells to efficiently secrete proteins like antibodies. We discovered that LTK had a drug binding site nearly identical to another kinase, ALK, and that ALK inhibitors inhibited LTK in cell types completely lacking ALK. Thus, we could use ALK inhibitors to block the crucial function of LTK. This was a completely different usage and drug action than previously described and patented. The new drug action and application were therefore patented. ITP is an autoimmune disease where existing drugs are often not sufficient for effective treatment, and where most patients relapse. There is an unmet medical need. We found that LTK was widely expressed in plasma cells, and that LTK inhibition was an effective way to selectively kill plasma cells in vitro and in immune-deficient mice that had received blood transfusions from humans. The innovation is of particular interest to inhibit plasma cells lacking CD20 and to reduce the level of harmful autoantibodies. We have submitted patent applications globally (PCT) and this has progressed to the national phase in the USA, Europe, Australia, Canada, China, Japan, and Korea. Patents are under processing. Further market and development plans are formulated.

The innovation project identified a new drug target for small molecule inhibitors, drugs that inhibit the kinase LTK for the treatment of autoimmune diseases such as immune thrombocytopenia (ITP). Autoimmune diseases are characterized by patients having plasma cells that secrete autoantibodies causing tissue damage. In ITP, patients often have autoantibodies that bind to and destroy platelets. ITP patients with low platelet counts risk developing fatal bleeding. We found that the drug target, LTK, is important for the function and survival of plasma cells, as LTK allows cells to efficiently secrete proteins like antibodies. We discovered that LTK had a drug binding site nearly identical to another kinase, ALK, and that ALK inhibitors inhibited LTK in cell types completely lacking ALK. Thus, we could use ALK inhibitors to block the crucial function of LTK. This was a completely different usage and drug action than previously described and patented. The new drug action and application were therefore patented. ITP is an autoimmune disease where existing drugs are often not sufficient for effective treatment, and where most patients relapse. There is an unmet medical need. We found that LTK was widely expressed in plasma cells, and that LTK inhibition was an effective way to selectively kill plasma cells in vitro and in immune-deficient mice that had received blood transfusions from humans. The innovation is of particular interest to inhibit plasma cells lacking CD20 and to reduce the level of harmful autoantibodies. We have submitted patent applications globally (PCT, WO2021083555A1) and this has progressed to the national phase in the USA, Europe, Australia, Canada, China, Japan, and Korea. Patents are under processing. Further market and development plans are formulated. This involves plans for a trial to test an LTK-inhibitor in ITP and plans to develop LTK-inhibitors for therapy of CLL, a B cell malignancy that has autoimmune features with plasma cells and secretion of autoantibodies (like the current project), and also proliferating CLL plasma blasts that are sensitive to LTK inhibition.