An Adaptive Design Study of MTX228

MTX228 was developed as a treatment for gastric ulcers but did not advance beyond phase 2 clinical trials because of lack of efficacy. Subsequently, MTX228 has been identified as an activator of Lyn kinase and was considered as a treatment for type 2 diabetes as an insulin sensitizer because of Lyn's interaction with insulin signaling molecules. More recently, Lyn has been identified as a critical regulator of beta-cell mass, with genetic and biochemical inactivation of Lyn provoking beta-cell death in isolated human islets and precipitated diabetes in mice, and activation of Lyn stimulating beta-cell survival and beta-cell proliferation. These findings strongly suggest that small molecule activators of Lyn, such as MTX228, could represent new therapeutic options to promote beta-cell regeneration in type 1 diabetes.

MTX228 has not been testing in clinical studies in type 1 diabetes and the optimal dose to use is not clear from the clinical trial in type 2 diabetes, where lower doses (100 mg once or twice daily) were more effective than higher doses (200 mg once or twice daily). The purpose of this study is to compare the effect of different doses of MTX228 in order to determine the most effective dose to move forward in a subsequent phase 2b study.