Groundbreaking Science

Despite blockbuster commercial success of several integrin-targeting antibodies, this class of receptor has remained elusive for oral small molecule drugs…until now.

Professor Timothy Springer and his post-doc, Albert Lin first cracked the puzzle by understanding the molecular mode of action that leads to the paradoxical agonistic responses that result in the negative clinical outcomes, rather than their intended antagonism. They later identified a new type of antagonistic integrin inhibitors that stabilize specific receptor conformations.

Morphic’s technology is powered by the in-depth knowledge on integrin structure, affinity regulation and dynamics, enabling the discovery of novel oral integrin inhibitors.

Our molecules are designed to prevent integrins from achieving disease-specific function and signaling through engaging appropriate receptor conformations.

Inactive Integrin in the Normal Tissue
Inactive Integrin in the Normal Tissue
Primed Integrin in the Diseased Tissue
Integrin in the Diseased Tissue Activated by a Small Molecule

In their native forms, the majority of integrins are refractory to crystallization, a process needed for X-ray structure elucidation due to their heavy glycosylation and conformational heterogeneity.

Morphic Therapeutic has exclusive rights to the Springer laboratory approach that allows robust determination of structures of integrin heterodimers at Morphic where we now have access to over 100 high-resolution integrin structures.

Graphics of a high-resolution integrin electron density map, like this one below

This technology has enabled the identification of proprietary chemotypes that modulate integrin conformations.

Electron density map