Next-Generation ETB Targeting CTLA-4

MT-8421 is an ETB candidate designed to preferentially destroy high CTLA-4-expressing Tregs in the tumor microenvironment (“TME”) relative to peripheral Tregs, which are lower CTLA-4 expressing, through a direct cell-kill mechanism independent of the effector cell presence that antibodies rely upon while not effecting Tregs in the periphery, the major mechanism of antibody-mediated autoimmune toxicity. Preclinical data from MT-8421 showed that in a transgenic mouse model expressing human CTLA-4 and bearing syngeneic subcutaneous tumors, MT-8421 treatment depleted immune suppressive Tregs in the TME but not in the periphery. MT-8421 was well tolerated in a non-human GLP primate toxicology study and achieved serum levels well-above projected IC₅₀ concentrations for Tregs in the TME. The IND for MT-8421 was accepted March 2023 and a Phase 1 study of MT-8421 is expected to initiate mid-year 2023.