Itolizumab-induced reduction of CD6 from T effector cells promotes the development and activity of T regulatory cells
CD6-ALCAM pathway confirmed as a target to prevent pathogenic T cell recruitment into inflamed organs
LA JOLLA, Calif.–(BUSINESS WIRE)–$EQ–Equillium, Inc. (Nasdaq: EQ), a clinical-stage biotechnology company focused on developing novel therapeutics to treat severe autoimmune and inflammatory disorders with high unmet medical need, today 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.
“Our data suggests that by treating T cells with itolizumab to significantly reduce surface levels of CD6, we are enhancing the potential for T regulatory cell development,” said Dr. Steve Connelly, chief scientific officer at Equillium. “This demonstrates that we are not only able to modulate the immune system by suppressing T effector cells but increasing the potential development and activity of T regulatory cells, resulting in an increased ratio of T regulatory cells to T effector cells. Additional translational data presented by our team suggests that the CD6-ALCAM pathway plays an important role in the migration of T cells through endothelial tissue and demonstrates that blockade of CD6 by itolizumab has the potential to prevent recruitment of pathogenic T cell, such as Th17, into inflamed organs. Collectively, these presentations suggest that the CD6-ALCAM pathway is an attractive target for autoimmune and inflammatory diseases and that itolizumab may be ideally suited to target this pathway.”
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
Presenting Author: Jeanette Ampudia, Scientist, Equillium, Inc.
Presentation Type: Poster Session
Poster Number: 532
Session Title: Immunoregulation-Mechanism of Action
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 (~2-fold) 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
Presenting Author: Dalena Chu, Scientist, Equillium, Inc.
Presentation Type: Poster Session
Poster Number: 300
Session Title: Immunoregulation-Infection and Immunity
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 FcγRI.
- 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
Presenting Author: Valeria Marrocco, Scientist, Equillium, Inc.
Presentation Type: Poster Session
Poster Number: 190
Session Title: They Come and They Go: A Leukocyte Migration Extravaganza
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.
All presentations are available on the Presentations page of Equillium’s website.
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 effector T cells while preserving regulatory T 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. Equillium acquired rights to itolizumab through an exclusive partnership with Biocon Limited.
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 immunomodulatory assets targeting immuno-inflammatory pathways. Itolizumab, a first-in-class monoclonal antibody that targets the CD6-ALCAM signaling pathway which plays a central role in the modulation of effector T cells, is currently in a Phase 3 study for patients with acute graft-versus-host disease (aGVHD) and is in a Phase 1b study for patients with lupus/lupus nephritis. EQ101, a first-in-class tri-specific cytokine inhibitor that selectively targets IL-2, IL-9, and IL-15, is Phase 2 ready and expected to begin enrolling patients in an alopecia areata study in the second half of 2022. EQ102, a bi-specific cytokine inhibitor that selectively targets IL-15 and IL-21, is ready for clinical development and expected to begin enrolling patients in a Phase 1 study anticipated to include normal healthy volunteers and celiac disease patients, in the second half of 2022.
For more information, visit www.equilliumbio.com.
Forward Looking Statements
Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements may be identified by the use of words such as “anticipate”, “believe”, “could”, “continue”, “expect”, “estimate”, “may”, “plan”, “outlook”, “future” and “project” and other similar expressions that predict or indicate future events or trends or that are not statements of historical matters. Because such statements are subject to risks and uncertainties, many of which are outside of the Company’s control, actual results may differ materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limited to statements regarding the potential benefit of treating patients with aGVHD or lupus/lupus nephritis with itolizumab, Equillium’s plans and expected timing for developing itolizumab including the expected timing of initiating, completing and announcing further results from the EQUATE, EQUIP, EQUALISE and EQUATOR studies, Equillium’s plans and expected timing for developing EQ101 and EQ102 including the expected timing of initiating, completing and announcing further results from Phase 2 and Phase 1 studies, respectively, the potential for any of Equillium’s ongoing or planned clinical studies to show safety or efficacy, Equillium’s anticipated timing of regulatory review and feedback, and Equillium’s plans and expected timing for developing its product candidates and potential benefits of its product candidates. Risks that contribute to the uncertain nature of the forward-looking statements include: uncertainties related to the abilities of the leadership team to perform as expected; Equillium’s ability to execute its plans and strategies; risks related to performing clinical studies; the risk that interim results of a clinical study do not necessarily predict final results and that one or more of the clinical outcomes may materially change as patient enrollment continues, following more comprehensive reviews of the data, and as more patient data become available; potential delays in the commencement, enrollment and completion of clinical studies and the reporting of data therefrom; the risk that studies will not be completed as planned; Equillium’s plans and product development, including the initiation and completion of clinical studies and the reporting of data therefrom; whether the results from clinical studies will validate and support the safety and efficacy of Equillium’s product candidates; changes in the competitive landscape; uncertainties related to Equillium’s capital requirements; and having to use cash in ways or on timing other than expected and the impact of market volatility on cash reserves. These and other risks and uncertainties are described more fully under the caption “Risk Factors” and elsewhere in Equillium’s filings and reports, which may be accessed for free by visiting EDGAR on the SEC web site at http://www.sec.gov and on the Company’s website under the heading “Investors.” Investors should take such risks into account and should not rely on forward-looking statements when making investment decisions. All forward-looking statements contained in this press release speak only as of the date on which they were made. Equillium undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.
Contacts
Investor Contact
Michael Moore
Vice President, Investor Relations & Corporate Communications
619-302-4431
ir@equilliumbio.com
Media Contacts
Aljanae Reynolds
Wheelhouse Life Science Advisors
areynolds@wheelhouselsa.com