α8 inhibition demonstrates efficacy in a cancer model refractory to radiation and checkpoint inhibition

Data provide increased rationale to explore integrin inhibition as a component in combination immunotherapy to drive anti-tumor response via TGFβ pathway

WALTHAM, MA, USA I November 15, 2021 I Morphic Therapeutic (Nasdaq: MORF), a biotechnology company developing a new generation of oral integrin therapies for the treatment of serious chronic diseases, announced the presentation of new data from its αvβ8 integrin inhibition program at the Society for Immunotherapy of Cancer (SITC) 2021 Annual Meeting. These new preclinical data, evaluating a monoclonal antibody targeting αvβ8, reinforce and build upon previous findings that αvβ8 inhibition can drive potent anti-tumor responses in tumor models refractory to current treatment modalities. αvβ8 is known to mediate the activation of tumor growth factor beta (TGFβ1/3). Morphic is developing oral small molecule inhibitors of the αvβ8 integrin which is expressed on cell types central to immune response and is a major contributor to tolerance and suppression of anti-tumor immunity.

“These SITC data show that Morphic’s αvβ8 inhibitors, in combination with radioimmunotherapy, significantly enhance efficacy in a syngeneic mouse preclinical model of advanced colon cancer that was non-responsive to radioimmunotherapy,” commented Bruce Rogers. PhD, Chief Scientific Officer of Morphic. “These results expand our understanding of the potential treatment modalities where addition of αvβ8 inhibition may be beneficial in tumors refractory to standard immunotherapy approaches.”

The research presented at SITC demonstrates that Morphic’s αvβ8 inhibitor, in combination with radioimmunotherapy (RIT), drove tumor response in a syngeneic mouse model refractory to radiotherapy and immune checkpoint blockade alone and in combination. In these data, the addition of αvβ8 inhibitors to RIT markedly increased tumor regression (P=0.0067) and survival (P<0.0001). In the group receiving the αvβ8 inhibitor in combination with RIT there were 8/10 complete responders compared with 3/10 receiving RIT alone. Irradiation of cells in vitro induced αvβ8 expression in dendritic cells that mediate tumor tolerance providing a mechanistic basis for findings.

Title
Inhibition of Integrin α8 in combination with low dose radiation induces antitumor effect in advanced immune checkpoint blockade refractory tumor model

Presenter
Natalia Blanco, PhD

Contributors
Megan Krumpoch, Michaela Mentzer, Vinod Yadav, Brianna Bannister, Dan Cui, Elizabeth Konopka, Dooyoung Lee, Fu-Yang Lin, Terence I. Moy, Eugene Nebelitsky, Qi Qiao, Inese Smutske, Charlotte A. Root, Patrick Allison, Sarah A. Krueger, Dawn Troast, Blaise Lippa, Bruce N. Rogers, Adrian S. Ray

The SITC poster is available on the Morphic website under the Investor tab.

About Morphic Therapeutic

Morphic Therapeutic is a biopharmaceutical company developing a new generation of oral integrin therapies for the treatment of serious chronic diseases, including autoimmune, cardiovascular, and metabolic diseases, fibrosis and cancer. In collaboration with AbbVie, Janssen, and Schrödinger, Morphic is advancing its pipeline and discovery activities using its proprietary MInT technology platform which leverages the Company’s unique understanding of integrin structure and biology. For more information, visit www.morphictx.com.

SOURCE: Morphic