Morphic demonstrates real-time visual of small molecule alpha4beta7 inhibition

Morphic Therapeutic announced the presentation of new data, using Spinning Disk Intravital Microscopy, IVM, that provides real-time, in vivo visualization of the impact of alpha4beta7 inhibition on lymphocyte trafficking in mouse gut-associated lymphoid tissues, GALT. These data were presented in a poster session at Digestive Disease Week, DDW, 2024 meeting. This real-time footage and the associated data for B cell movement clearly demonstrate that MT-108, a potent and selective small molecule alpha4beta7 inhibitor, leads to increased velocity and flux of rolling lymphocytes. This activity subsequently prevents lymphocyte migration into gut tissue, including Peyer’s patches, which is a key component of inflammatory bowel disease. Notably, MT-108 impacted B cell trafficking with similar speed of onset and efficacy as the anti-alpha4beta7 blocking antibody DATK32, a murine analog of the monoclonal antibody vedolizumab. The onset and extent of alpha4beta7 inhibition can be visualized by the increased velocity of B cells when comparing the lymphocyte movement prior to compound administration. In the absence of inhibitor, cells are slowed by their binding of alpha4beta7 with the ligand MAdCAM-1. Following administration of MT-108, the immune cells transit more quickly through the vessel as a result of inhibition of alpha4beta7-mediated adhesion and fewer cells are seen affixed to vessel walls.