CD6 contributes to cell adhesion/migration both through direct ligand interactions with activated leukocyte cell adhesion molecule (ALCAM) and through the stabilization of cell membrane VLA4

Blockade of CD6 through itolizumab prevents the trans-endothelial migration of effector T cells

Data supports the differentiated mechanism of action of itolizumab

Equillium, Inc. (Nasdaq: EQ), a clinical-stage biotechnology company focused on developing novel therapeutics to treat severe autoimmune and inflammatory disorders, today announced that a poster was presented at IMMUNOLOGY2024, the annual meeting of The American Association of Immunologists. The meetings are taking place at McCormick Place Convention Center in Chicago, Illinois, May 3 – 7.

“Our data demonstrates that CD6 contributes to cell adhesion/migration both through direct ligand interactions with ALCAM and through the stabilization of cell membrane VLA4, and that these functions can be abrogated by itolizumab,” said Dr. Stephen Connelly, chief scientific officer at Equillium. “We previously showed that blockade of CD6 prevents the trans-endothelial migration of effector T cells and this new data further elucidates the molecular mechanism. Moreover, our data continues to demonstrate that increased levels of CD6 facilitate the migration of pathogenic effector T cells into inflamed tissues and that itolizumab can modulate not only their activity, but trafficking too.”

Title: Surface CD6 regulates T cell adhesion and migration through direct ligand interaction and stabilization of VLA4

Lead Author: Valeria Marrocco, Senior Scientist, Equillium, Inc.

Presentation Type: Poster Session

Poster Number: P713

Abstract ID: 4364

Session Title: Migration and Adhesion in Inflammation, Cancer, and Metabolic Disorders

Key Highlights, Summaries & Conclusions from Presentation:

• Itolizumab not only blocks the binding of CD6 to ALCAM, but it also induces the stripping of the receptor on the T cells’ membrane in the presence of antigen presenting cells, generating CD6 low T cells.
• Reduction of CD6 on T cells or blocking of ALCAM on the human umbilical vein endothelial cells (HUVEC), prevents the adhesion of Effector T cells to the endothelial monolayer.
• Itolizumab treatment significantly reduced the trans-endothelial migration of pathogenic T cells, with high correlation of effector T cells’ migration index with the CD6 levels on the cell surface.
• Itolizumab treatments reduced the gene expression important for cell motility and downregulated VLA4 integrin levels on the cell surface and the total protein levels.
• Data identifies a new role of the CD6-ALCAM pathway in adhesion and trans-endothelial migration of effector T cells and demonstrated that CD6 expression at the membrane is required for the expression and stabilization of the integrin VLA4. This suggests a direct role of the CD6-ALCAM pathway and indirect T cell mobility regulation through downregulation of VLA4.

The poster presentation is available on the Presentations page of Equillium’s website under the “Itolizumab MOA” tab.

About Itolizumab

Itolizumab is a clinical-stage, first-in-class anti-CD6 monoclonal antibody that selectively targets the CD6-ALCAM signaling pathway to selectively downregulate pathogenic T effector cells while preserving T regulatory cells critical for maintaining a balanced immune response. This pathway plays a central role in modulating the activity and trafficking of T cells that drive a number of immuno-inflammatory diseases.

About Equillium

Equillium is a clinical-stage biotechnology company leveraging a deep understanding of immunobiology to develop novel therapeutics to treat severe autoimmune and inflammatory disorders with high unmet medical need. The company’s pipeline consists of the following novel first-in-class immunomodulatory assets and product platform targeting immuno-inflammatory pathways. EQ101: a selective tri-specific cytokine inhibitor targeting IL-2, IL-9, and IL-15; currently under evaluation in a Phase 2 proof-of-concept clinical study of patients with alopecia areata being conducted in Australia and New Zealand by Equillium’s Australian subsidiary as the trial sponsor. EQ302: an orally delivered, selective bi-specific cytokine inhibitor targeting IL-15 and IL-21; currently in pre-clinical development. The multi-cytokine platform: generates rationally designed composite peptides that selectively block key cytokines at the shared receptor level targeting pathogenic cytokine redundancies and synergies while preserving non-pathogenic signaling. Itolizumab: a monoclonal antibody that targets the CD6-ALCAM signaling pathway which plays a central role in the modulation of effector T cells; currently under evaluation in a Phase 3 clinical study of patients with acute graft-versus-host disease (aGVHD) and recently completed a Phase 1b clinical study of patients with lupus/lupus nephritis. Equillium acquired rights to itolizumab through an exclusive partnership with Biocon Limited and has entered a strategic partnership with Ono Pharmaceutical Co., Ltd., for the development and commercialization of itolizumab under an option and asset purchase agreement.

For more information, visit www.equilliumbio.com.

Forward Looking Statements

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