The Journey to Oral Integrins

The Promise of Integrins

The therapeutic potential of integrins has been widely recognized for years because of their central roles in almost all phases of human biology as well as many diseases. Several intravenous integrin inhibitors have been approved by the U.S. Food and Drug Administration for the treatment of inflammatory bowel disease (Entyvio®, Tysabri®), multiple sclerosis (Tysabri®), psoriasis (Raptiva®), acute coronary syndrome (Reopro®, Aggrastat®, Integrilin®), and dry eye disease (Xiidra®).

Oral therapies: setbacks and solutions

The infusible or topical nature of approved integrin therapies significantly restrict their therapeutic potential. Current integrin inhibitors are limited in  earlier lines of treatment. This significant medical need drove clinical development of several oral integrin drug candidates which all presented toxicity in clinical studies, resulting in the termination of their development.

Morphic’s foundational scientific partner, the Springer Laboratory, was the first to identify the biology that led to this toxicity and develop a new chemical class capable of addressing the issue. These successes are now leveraged by Morphic, which is focused on using its integrin discovery platform to discover and develop first-in-class oral small molecule integrin therapeutics across a range of disease areas.

What did previous attempts get wrong?

Previous attempts to develop oral integrins saw repeated toxicity and clinical failure. After significant research, the Springer laboratory made the crucial discovery that the drug candidates, all integrin antagonists, were inducing agonistic responses, worsening disease. The Springer team identified the molecular mode of action and conformational states involved, and developed a new type of antagonistic integrin inhibitor to stabilize the desired integrin conformation.

Morphic benefits from the decades of integrin expertise built at the Springer laboratory through an exclusive license. Morphic’s candidates are designed to prevent integrins from achieving disease-specific function and signaling through stabilizing appropriate integrin conformations.

Read more about Morphic’s unique platform and integrin class development strategy via the link below.

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