Morphic is leveraging a proprietary integrin discovery platform to discover and develop first-in-class oral small molecule integrin therapeutics across a range of disease areas with an initial focus on autoimmune diseases, fibrosis and cancer.
The incidence of autoimmune disease is increasing in the industrialized world, including conditions such as Ulcerative Colitis, Crohn’s disease, psoriasis, rheumatoid arthritis and systemic lupus erythematosus.
The infiltration of immune cells into tissues is central to any inflammatory response, including autoimmunity. In the case of IBD, inflammatory T cells that express α4β7 enter the gut tissue by binding to MADCAM-1. Inhibiting this interaction in the bloodstream is a validated approach to treating IBD (UC and Crohn’s Disease), and is the primary mode of action of our lead program, MORF-057. In addition, integrins facilitate the retention of immune cells at sites of chronic inflammation by binding to components of the extracellular matrix. Blocking these integrins may therefore repress pathological autoimmunity across many conditions.
Though there are many disparate causes, human fibrotic diseases represent a significant health challenge globally and frequently result in organ dysfunction and ultimately death.
The uncontrolled and progressive deposition of fibrotic tissue (scar tissue) is the cause of several common conditions affecting the lungs, liver, kidneys, skin or other tissues and can lead to organ dysfunction and even death. Several integrins have been implicated in this process and through a deep understanding of integrin biology, we may be able to selectively arrest this pathologic process by modulating their activity in the relevant organ system.
Cancer is among the leading causes of death worldwide, and responsible for nearly 10 million deaths annually.
The immune system plays a central role in identifying and eliminating pre-cancerous and cancerous cells, via both innate and adaptive mechanisms. However, many cancers have evolved methods to evade this normal immunosurveillance which enables further cancer growth and differentiation. Many integrins, such as αVβ8, play a central role in this process by activating select isoforms of TGFβ in the tumor microenvironment, thus inhibiting the immune response in those tissues. Inhibiting αVβ8 may therefore sensitize these tumors to the normal immunosurveillance and/or checkpoint inhibitors.
Morphic has developed the MInT (Morphic Integrin Technology) platform, an effective drug discovery platform that combines our core capabilities across integrin biology, structural analysis, therapeutic design, and translational development with ongoing input from the Springer laboratory, the long-term integrin research leader. Morphic’s discovery capabilities span every member of the 24-member integrin family and include both inhibitors and activators of integrin activity informed by Morphic’s exclusive know-how in the development of molecules that stabilize specific integrin receptor conformations. Each unique compound in our >16k library paired with our strong computational partnership with Schrodinger informs new designs against current and future integrin targets creating a virtuous cycle of drug discovery.