EQ102 selectively blocks IL-15 and IL-21 signaling while preserving signaling of other gamma chain family members
Data suggest that selective blockade of IL-15 and IL-21 inhibits the synergistic signaling that mediates NK and T cell responses in multiple immune disorders including celiac disease
Equillium, Inc. (Nasdaq: EQ), 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, today announced a poster was presented over the weekend at IMMUNOLOGY2023, the annual meeting of The American Association of Immunologists. The meetings are taking place at the Walter E. Washington Convention center in Washington, DC, May 11 – 15.
“We know that signaling of IL-15 and IL-21 is important in driving T and NK cell responses and that each promote cytolytic activity and interferon gamma production, but that blocking only one of these cytokines is unlikely to improve disease outcome,” said Dr. Cherie Ng, vice president of research at Equillium. “Equillium is developing EQ102 to selectively and synergistically block both IL-15 and IL-21 signaling, without affecting other gamma chain family members. We believe this selective blockade could be effective in treating celiac disease, known to be driven by elevated levels of IL-15 and IL-21 that drive the T and B cell responses culminating in tissue damage in these patients.”
Details of EQ102 Data Presented
Title: γc receptor antagonist, EQ102, prevents the NK and T cell-mediated responses driven by IL-15 and IL-21
Presenting Author: Phoi Tiet, Senior Research Associate, Equillium, Inc.
Presentation Type: Poster Session
Poster Number: P854
Session Title: Molecular Mechanisms of Cytokine Function
Key Highlights, Summaries & Conclusions from Presentation:
- Synergistic signaling of IL-15 and IL-21 is important in driving pathogenic T and NK cell responses in multiple inflammatory diseases.
- IL-15 and IL-21 each promote cytolytic activity and IFNγ production but can also synergistically enhance the function of other cytotoxic cytokines. Consequently, blockade of only IL-15 or only IL-21 is not likely to improve disease outcome in pathologic environments.
- EQ102 is a multi-cytokine inhibitor that selectively blocks IL-15 and IL-21 signaling while preserving signaling of other γc family members.
- Co-stimulation of IL-15 and IL-21 enhanced proliferation, activation, and IFNγ, Granzyme A, Granzyme B and Perforin production above single cytokine conditions and EQ102 treatment effectively inhibits the IL-15/IL-21 co-stimulatory cytolytic responses of these cell populations.
- Results suggest that selective blockade of IL-15 and IL-21 by EQ102 inhibits the synergistic signaling that mediates NK and T cell responses in multiple immune disorders.
EQ102 has been shown to inhibit both IL-15 and IL-21 induced signaling pathways in celiac patient-derived intraepithelial cytotoxic T-Lymphocytes and key genes for tissue destruction in patient-derived organoid cultures. Similarly, in pre-clinical studies, EQ102 has demonstrated the prevention of intestinal tissue damage in a humanized mouse model of gastrointestinal inflammation.
About Multi-Cytokine Platform and EQ101 & EQ102
Our proprietary 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. This approach is expected to avoid the broad immuno-suppression and off-target safety liabilities that may be associated with other therapeutic classes, such as Janus kinase 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 platform assets include EQ101, a first-in-class, selective, tri-specific inhibitor of IL-2, IL-9 and IL-15, and EQ102, a first-in-class, selective, bi-specific 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 first-in-class immunomodulatory assets targeting immuno-inflammatory pathways. EQ101: a tri-specific cytokine inhibitor that selectively targets IL-2, IL-9, and IL-15; currently under evaluation in a Phase 2 proof-of-concept clinical study of patients with alopecia areata. EQ102: a bi-specific cytokine inhibitor that selectively targets IL-15 and IL-21; currently under evaluation in a Phase 1 first-in-human clinical study to include healthy volunteers and celiac disease patients. 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 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
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 Equillium’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 benefit of treating patients with celiac disease with EQ102 and Equillium’s plans for developing EQ102. Risks that contribute to the uncertain nature of the forward-looking statements include: Equillium’s ability to execute its plans and strategies; risks related to performing clinical studies; whether the results from clinical studies will validate and support the safety and efficacy of Equillium’s product candidates. 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 the Securities and Exchange Commission’s website at www.sec.gov and on Equillium’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, except as required by law.
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