Morphic : DDW 2024 A4B7 Inhibition IVM Poster

Morphic Demonstrates Novel Real-time Visualization of Small Molecule α4β7 Inhibition of

Gut Trafficking Cells

-α4β7 Inhibition Rapidly Increases the Rolling Velocity and Flux of B Cells in Gut-associated

Lymphoid Tissues-

-Impact of Potent and Selective Small Molecule Inhibitor Comparable to Monoclonal Antibody

Activity-

-Preclinical Findings Presented at Digestive Disease Week 2024-

WALTHAM, Mass., May 21, 2024 --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, using Spinning Disk Intravital Microscopy (IVM), that provides real-time,in vivo visualization of the impact of α4β7 inhibition on lymphocyte trafficking in mouse gut-associated lymphoid tissues (GALT). These data were presented in a poster session at Digestive Disease Week (DDW) 2024 meeting.

This real-time footage and the associated data for B cell movement clearly demonstrate that MT- 108, a potent and selective small molecule α4β7 inhibitor, leads to increased velocity and flux of rolling lymphocytes. This activity subsequently prevents lymphocyte migration into gut tissue, including Peyer's patches, which is a key component of inflammatory bowel disease. Notably, MT-108 impacted B cell trafficking with similar speed of onset and efficacy as the anti-α4β7 blocking antibody DATK32, a murine analog of the monoclonal antibody vedolizumab. The onset and extent of α4β7 inhibition can be visualized by the increased velocity of B cells when comparing the lymphocyte movement prior to compound administration. In the absence of inhibitor, cells are slowed by their binding of α4β7 with the ligand MAdCAM-1. Following administration of MT-108, the immune cells transit more quickly through the vessel as a result of inhibition of α4β7-mediated adhesion and fewer cells are seen affixed to vessel walls.

Videos showing the changes in leukocyte movement in vivo can be viewed for the small molecule α4β7 inhibitorand the test vehicle. The poster presented at DDW can be found on the Morphic website.

"These new data demonstrate not only that a small molecule α4β7 inhibitor drives changes comparable to a monoclonal antibody but also provide stunning real time in vivo visualization of this activity. Unlike other in vivo models, IVM enables the viewer to experience visually the changes Morphic's small molecule α4β7 inhibitor rapidly imparts on lymphocyte trafficking to gut tissues and allows the scientist to quantify those effects," commented Bruce Rogers, PhD, President of Morphic Therapeutic. "Importantly, the onset of activity, and efficacy of our small

molecule α4β7 inhibitor are virtually identical to the effects on cells by DATK32, a murine analog of ENTYVIO™."

DDW Session: 9370

Poster Tu1738: Real-Time Inhibition Of Integrin α4β7 By A Small Molecule Inhibitor Impairs B Lymphocyte Adhesion In Murine Peyer's Patches

Authors: Allison Sang1, Björn Petri2, Naresh S. Redhu1, Dooyoung Lee1, Danielle Granata1, Michael Rowe1, Bryce Harrison1, Matthew Bursavich1, Bryan Goodwin1, Bruce N. Rogers1, Kamala D Patel3, and Jamie Wong1

1Morphic Therapeutic, 35 Gatehouse Drive, Waltham, Massachusetts, USA, 02451,

2Department of Microbiology, Immunology and Infectious Diseases, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada,

3Department of Physiology and Pharmacology, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.

ENTYVIO is a registered trademark of Millenium Pharmaceuticals, Inc.

About Morphic Therapeutic

Morphic Therapeutic is a biopharmaceutical company developing a portfolio of oral integrin therapies for the treatment of serious chronic diseases, including autoimmune, cardiovascular, and metabolic diseases, fibrosis, and cancer. Morphic is also advancing its pipeline and discovery activities in collaboration with Schrödinger 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. 

Cautionary Note Regarding Forward-Looking Statements

This press release contains "forward-looking" statements within the meaning of the Securities Act of 1933, as amended, the Securities Exchange Act of 1934, as amended, and of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to: the MInT platform's ability to discover drug candidates and our plans to develop and commercialize oral small-molecule integrin therapeutics, including MT-108 which is not expected to be developed or commercialized. Statements including words such as "believe," "plan," "continue," "expect," "will be," "develop," "signal," "potential," "anticipate" or "ongoing" and statements in the future tense are forward-looking statements. These forward-looking statements involve risks and uncertainties, as well as assumptions, which, if they do not fully materialize or prove incorrect, could cause our results to differ materially from those expressed or implied by such forward-looking statements. Forward-looking statements are subject to risks and uncertainties

that may cause our actual activities or results to differ significantly from those expressed in any forward-looking statement, including risks and uncertainties in this press release and other risks set forth in our filings with the Securities and Exchange Commission, including, among others, our or a partner's ability to complete a current or future clinical trial of any of our current or future product candidates, our ability to develop or obtain regulatory approval for or commercialize any product candidate, our ability to protect our intellectual property, and the sufficiency of our cash, cash equivalents and investments to fund our operations. These forward-looking statements speak only as of the date hereof and we specifically disclaim any obligation to update these forward-looking statements or reasons why actual results might differ, whether as a result of new information, future events or otherwise, except as required by law.

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Contacts

Morphic Therapeutic Chris Erdman [e-mail]617.686.1718