Opportunities in high unmet disease areas
Morphic Therapeutic is focused on three main therapeutic areas where integrin antagonists could have a major impact on human suffering.
Fibrosis and Immunooncology
Sustained organ injury leads to fibrosis, a pathological process characterized by the formation of excessive connective tissue.
The pro-fibrotic cytokine TGF-β activates fibroblasts, cells that synthesize the extracellular matrix and collagen.
Several members of αv integrin subfamily can activate TGF-β directly. Thus, pharmacological inhibition holds promise in treatment of liver, kidney and lung fibrosis.
In addition, excessive TGF-β signaling promote immunosuppressive microenviroment in the sites of oncogenic growth and dampen anti-tumor immune responses. Therefore, selective inhibition on TGF-β via integrin blockade can be a powerful therapeutic approach in immunooncology.
The aberrant activation of the immune system against self-tissues leads to local or systemic autoimmunity. The infiltration of lymphocytes into inflamed tissues is central to the excessive inflammatory response.
Integrins belonging to the α4 and β2 subfamilies control the interactions that allow immune cells to reach sites of inflammation. In addition, collagen-binding integrins facilitate the retention of immune cells in the sites of chronic inflammation.
Blocking these integrins could repress pathological Immunity across many autoimmune conditions.
Vasculogenesis and angiogenesis are the key mechanisms for the formation and repair of many human organs including blood vessels, eye and renal microvasculature.
Integrins belonging to the αv and β1 subfamilies control these processes by anchoring vasculature cells to extracellular matrix that provides structural and biochemical support for their migration, proliferation, differentiation and survival.
A dysregulation of these processes is common in heart, kidney and eye diseases, as well as in solid tumors and achieving vascular normalization through integrin inhibition can become an effective therapeutic strategy.