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Equillium announced that the European Hematology Association EHA has published an abstract highlighting the Phase 3 EQUATOR study in first-line acute graft-versus-host disease aGVHD. The abstract discusses acute graft-versus-host disease aGVHD being a major cause of morbidity and mortality following allogeneic hematopoietic stem cell transplant allo-HSCT and that there is no approved first-line treatment, where corticosteroids remain standard of care. Itolizumab, a humanized IgG1 monoclonal antibody that binds CD6 and blocks interaction with activated leukocyte cell adhesion molecule ALCAM to inhibit T effector cell activity and trafficking to target organs, represents a promising therapeutic approach to treat aGVHD, as suggested by safety and efficacy results from the Phase 1b EQUATE study. These results and benefit-risk profile led to the currently enrolling Phase 3 EQUATOR study, a randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of itolizumab in combination with corticosteroids for the treatment of first-line aGVHD.

Equillium announced that three posters were presented over the weekend at IMMUNOLOGY2022, the annual meeting of The American Association of Immunologists. The meetings are taking place at the Oregon Convention Center in Portland, Oregon, May 6 - 10, 2022. Itolizumab is a first-in-class anti-CD6 monoclonal antibody that selectively targets the CD6-ALCAM pathway, which plays a central role in modulating both the activity and trafficking of the pathogenic T cells driving a number of immuno-inflammatory diseases. Details of Itolizumab Data Presented Title: CD6 - a costimulatory receptor at the nexus of Teff / Treg development: Key Highlights, Summary and Conclusions from Presentation: First study to directly characterize the role of CD6 in the development and activity of T regulatory cells. T regulatory cells derived from CD6 low cells had greater co-expression of FOXP3 and HELIOS vs. T regulatory cells derived from isotype-treated CD6 high cells. T regulatory cells possessed greater suppressive function, with an increase of at least 50% greater inhibition of proliferation and cytokine release by T responder cells than T regulatory cells derived from CD6 high cells. CD6 low T regulatory cells were able to suppress T responder cell production of pro-inflammatory cytokines by 60% - 90% compared to CD6 high T regulatory cells. Data suggests that reduced levels of cell surface CD6 facilitate the development of T regulatory cells with greater stability and suppressive activity, and that modulating the levels of CD6 may increase the T regulatory to T effector cell ratio in patients with autoimmune and inflammatory diseases. Title: Modulating levels of cell surface CD6 is a novel mechanism for regulating T cell activity. Key Highlights, Summary and Conclusions from Presentation: CD6 high cells are highly pathogenic and levels of CD6 have been implicated in numerous autoimmune and inflammatory diseases including multiple sclerosis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, and acute graft-versus-host disease. Itolizumab-induced CD6 cleavage from the surface of T cells occurs through a transcellular event between a CD6 positive T cell and a CD14 positive monocyte. This cleavage event is mediated by functional Fc receptor binding of itolizumab to FcgammaRI. The loss of the extracellular domains of CD6 from the surface results in T cells that are hyporesponsive and less alloreactive to T cell stimulation. These results further support targeting CD6 as an effective means to inhibit pathogenic T cell activity in the treatment of autoimmune and inflammatory diseases as CD6 cleavage results in prolonged modulation of T cell activity. Title: The CD6-ALCAM pathway selectively modulates pathogenic T cell migration. Key Highlights, Summary and Conclusions from Presentation: CD4 positive and CD8 positive T cells that migrate in response to CXCL12, express higher levels of CD6 and that the amount of migration correlates with levels of CD6 expression, suggesting that CD6 is engaged during T cell migration across the endothelial monolayer. Decreasing CD6 expression led to decreased migration of effector memory T cells and terminally differentiated effector memory T cells while migration of T regulatory cells was unaffected, thus suggesting that targeting CD6 in autoimmune and inflammatory diseases would decrease infiltration of pathogenic T cells while still permitting modulation of the immune response by T regulatory cells. Th17 cells were stained from the total peripheral blood mononuclear cells population that migrated in response to CXCL12. Data showed a reduction of the migration of those cells after blocking the CD6-ALCAM pathway with itolizumab. This data suggests that CD6-ALCAM pathway is involved in the movement of T cells through the endothelial tissues and confirms CD6 as a target to prevent pathogenic T cell recruitment into inflamed organs.