Integrins in Human Disease

Integrins have vital roles in a diverse set of human diseases, including platelet disorders, atherosclerosis, cancer, osteoporosis, fibrosis, retinopathy, macular degeneration, and various autoimmune and chronic inflammatory diseases.

Morphic Therapeutic is focusing on three related therapeutic areas of high unmet medical need by combining our innovative platform and deep knowledge in integrin biology.  Morphic’s unparalleled know-how and experience has enabled the formation and advancement of an exciting portfolio of transformative integrin-based therapies.

Our ever-growing technology platform and domain knowledge has prepared us for rapid success in the integrin class of targets and beyond.

Autoimmune Diseases

The aberrant activation of the immune system against self-tissues leads to local or systemic autoimmunity.  The incidence of autoimmune disease is increasing in the industrialized world. Numerous diseases are the result of aberrant autoimmunity, such as ulcerative colitis, Crohn’s disease, psoriasis and systemic lupus erythematosus.

The infiltration of lymphocytes into inflamed tissues is central to any inflammatory response including those in autoimmunity.  Integrins belonging to the α4 and β2 subfamilies control the interactions that allow immune cells to migrate from circulation to reach sites of inflammation.  In addition, collagen-binding integrins facilitate the retention of immune cells at sites of chronic inflammation.  Blocking these integrins can repress pathological immunity across many autoimmune conditions.

Fibrosis

Sustained organ injury leads to uncontrolled fibrosis, a pathological process characterized by the formation of excessive extracellular matrix (ECM).  Fibrosis is a common feature of most chronic diseases involving tissue injury and affects multiple organs, such as lung, liver, skin, and kidney. The replacement of normally functional cells with architecturally distorted scar tissue greatly impacts the progressive loss of organ function and eventually leads to organ failure.

The pro-fibrotic cytokine TGF-β is a key regulator of fibrosis, but the attempts to globally suppress its activity has suffered from a narrow therapeutic index.  Several members of RGD-binding integrins play a dominant role in local activation of TGF-β directly in disease tissues.  Thus, pharmacological inhibition of these integrins is a key strategy for treating chronic fibrotic diseases with significant advantage over TGF-β inhibitors.

Cancer

Cancer is the leading cause of death in the Western world. Recent advances in immuno-oncology are changing the standard of care of many types of cancers but only a fraction of patients respond to the new treatment. There are significant gaps in the treatment armamentarium.

Excessive, local TGF-β signaling promotes an immunosuppressive tumor microenvironment (TME) leading to poorer prognosis in patients. This pathway impacts both immune and non-immune cell types to support tumor growth and greatly reduce the potential of anti-tumor immune responses. Therefore, selective inhibition of TGF-β activating integrins offers a significant opportunity to reduce tumor immune tolerance and be a powerful therapeutic approach in immuno-oncology.

Pipeline

Morphic is developing highly differentiated molecules for the treatment of autoimmune diseases, fibrotic diseases, and cancer. We have created a balanced portfolio of novel and highly validated targets.