Morphic Therapeutic brought x-ray crystallography in-house: Here’s why

In today’s capital efficient environment, why would Morphic decide to bring crystallography capabilities in-house?

The majority of Integrins have been refractory to structural characterization, due to heavily glycosylated, heterodimeric metalloproteins composed of many flexible domains and interdomain linkers. The Springer lab is the only lab that has been successful in crystallizing multiple different integrations.

Albert-cropGiven this we knew up front that this would be a very challenging piece of our science to externalize but with the expertise of Albert Lin, an inventor of our technology and postdoc from Tim’s lab, we thought it may be possible to outsource under his leadership.

Even with Albert’s assistance, no outside vendor was making progress.  Since our focus at Morphic is effective structure based drug design of these challenging targets, waiting around for structures was not an option!

December 2015

“How long does it take to get an Integrin structure?”

Albert said, “3 months to Never.

It took him just 2 months.

Any further Crystallography work was coming in-house.

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TL1A and IL-23

Morphic is leveraging its structural biology expertise and medicinal chemistry capabilities to develop small molecule therapeutic candidates against non-integrin targets including TL1-A and IL-23. Inhibition of these pathways have potential as treatments for IBD through monotherapy and possibly in combination with other IBD treatment mechanisms including α4β7 inhibition.

α5β1

Morphic is developing small molecule inhibitors of the integrin α5β1 based on research demonstrating that fibronectin integrin inhibition suppresses pulmonary arterial smooth muscle cell proliferation. Potential indications include severe pulmonary hypertensive disease including pulmonary arterial hypertension.

Integrin Partnership: Janssen

Morphic entered a research partnership with Janssen in 2019 to discover inhibitors of undisclosed integrin targets. In 2021, this partnership was expanded to include an antibody activator of an integrin target, extending the application of Morphic’s knowledge of integrin biology into modalities beyond small molecules. The antibody activator program is the focus of our collaboration with Janssen today.

Undisclosed Targets

Morphic is leveraging the MInT Platform to discover therapeutically relevant small molecule inhibitors of targets across the integrin family to treat autoimmune diseases, cancer and fibrotic diseases.

Undisclosed Target for Pulmonary Arterial Hypertension

Morphic is deploying the MInT Platform to create small molecule inhibitors of an undisclosed integrin target for evaluation as a potential treatment for pulmonary arterial hypertension (PAH). PAH is a devastating, usually fatal disease characterized by elevated mean pressures in the pulmonary artery and associated with lung and heart dysfunction. Morphic’s PAH program is in preclinical development.

αvβ8 (MORF-088)

Morphic is developing small molecule inhibitors of the integrin αvβ8 for potential uses in myelofibrosis and a combination immuno-oncology approach for the treatment of solid tumors. αvβ8 is known to activate selective isoforms of TGF-β and Morphic has demonstrated that αvβ8 inhibition can drive increased platelet production and potentiate immune checkpoint blockade and potentially drive responses in checkpoint refractory tumors. Morphic’s αvβ8 inhibitors are in preclinical development.

Next Gen α4β7 Inhibitors

Morphic is developing a family of next generation α4β7 small molecule inhibitors with enhanced attributes using the MInT Platform. These candidates have distinct chemical properties from our first-generation inhibitors with differentiated selectivity, potency, and pharmacokinetic profiles. Morphic’s next generation α4β7 inhibitors are currently in preclinical development.