Results demonstrate the use of selective inhibitors of multiple key cytokines as an effective strategy in treating autoimmune diseases driven by T and NK cells
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 data presented at the annual La Jolla Immunology Conference. The research highlights the potential for multi-cytokine inhibitors such as EQ101 and EQ102, as potentially effective strategies for the treatment of certain autoimmune diseases.
“The complexity of cytokine signaling to regulate immune homeostasis presents unique drug development challenges when treating disease,” said Steve Connelly, chief scientific officer at Equillium. “EQ101 and EQ102 are both first-in-class multi-cytokine inhibitors that provide selective targeting of biological redundancy and synergy at the receptor level, which has significant advantages over other approaches, including JAK inhibition. The results shown here demonstrate the effects of EQ101 and EQ102 in the modulation of important biology relevant to several autoimmune and inflammatory diseases. We look forward to initiating a Phase 2 clinical study of EQ101 in subjects with alopecia areata, and a Phase 1 first-in-human study of EQ102 in normal healthy volunteers – as well as celiac patients – both by the end of this year.”
Title: EQ101 and EQ102, selective multi-cytokine antagonists, inhibit cytotoxic T cell and NK activity
Author: Phoi Tiet, Senior Research Associate, Equillium, Inc., et al.
The presentation highlights important roles of cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells in the pathogenesis of various autoimmune and inflammatory diseases, and their activity being driven by multiple cytokines. For this research, human peripheral blood mononuclear cells (PBMCs) were stimulated with anti-CD3 and CD28 antibodies, rested overnight, labeled with a proliferation dye, treated with EQ101 or EQ102, and stimulated with IL-15 for 72 hours, then analyzed for surface activation markers by flow cytometry. Treatment of PBMCs with EQ101 or EQ102 resulted in an approximate 50% decrease in proliferation of CD4 T cell subsets, and an approximate 40% decrease of CD8 subsets. In addition, an approximate two-fold reduction of the cytotoxic NK cell population was observed with EQ101 and EQ102 treatments. Analysis revealed that EQ101 and EQ102 inhibited the production of CD4/CD8 relevant cytokines IL-6, IL-10, IFN-γ, IL-22, IL-17F, TNF-α and Fas/FasL and that production of perforin, granzyme A, granzyme B, and granulysin, secreted by CTLs and NK cells, was also significantly reduced. These results demonstrate that the use of selective inhibitors for multiple key cytokines can be an effective strategy in treating autoimmune diseases driven by T and NK cells.
The poster is available under the Multi-Cytokine Inhibition tab of the Presentations page of the Technology section of the company website.
About Multi-Cytokine Platform: EQ101 & EQ102
Our proprietary multi-cytokine platform (MCP) 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. This approach provides multi-cytokine inhibition at the receptor level and is expected to avoid the broad immuno-suppression and off-target safety liabilities that may be associated with other therapeutic classes, such as JAK inhibitors. Many immune-mediated diseases are driven by the same combination of dysregulated cytokines, and we believe identifying the key cytokines for these diseases will allow us to target and develop customized treatment strategies for multiple autoimmune and inflammatory diseases.
Current MCP assets include EQ101, a first-in-class, tri-specific inhibitor of IL-2, IL-9 and IL-15, and EQ102, a first-in-class, selective inhibitor of IL-15 and IL-21.
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 fourth quarter 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 fourth quarter 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 benefits of using our multi-cytokine platform to develop treatments for patients with certain autoimmune and inflammatory diseases, 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.
Vice President, Investor Relations & Corporate Communications