Dual and synergistic signaling of IL-15 and IL-21 robustly augments NK and CD8 T cell responses

Highlights importance of dual inhibition or activation for therapeutic approaches

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, today announced that a poster was presented over the weekend at the 39th Annual Meeting of the Society for Immunotherapy of Cancer. The conference took place at the George R. Brown Convention Center in Houston, Texas from November 6 to 10, 2024.

“These data provide deeper insights into the dual and synergistic signaling of IL-15 and IL-21 that drives aggressive T and NK cell responses that promote the cytolytic activity and interferon gamma production observed in multiple inflammatory diseases,” said Dr. Stephen Connelly, chief scientific officer at Equillium. “As such, in the context of treating inflammatory disease, or augmenting anti-tumor responses, it would be optimal to inhibit or activate both cytokines in a single agent and is a focus of the multi-cytokine platform at Equillium.”

Title: Interleukin (IL)-15 and IL-21 synergistically enhance NK and CD8+ T cell responses Presenting Author: Phoi Tiet, Senior Research Associate, Equillium, Inc. Poster Number: 908

Key Highlights, Summaries & Conclusions from Presentation:

  • Synergistic signaling of IL-15 and IL-21 enhanced markers of activity including CD25, PD-1, Tim-3 and ICOS, in addition to increased production of granzyme A, granzyme B and perforin, indicating that these two cytokines play important roles in activation, development, and survival of NK and CD8+ T cells.
  • IL-15 and IL-21 cooperatively amplified CD8+T and NK cytolytic activities and IFNγ production, suggesting that targeting these two pathways can amplify cell-based immunity.
  • Preliminary evaluation of IL-15 and IL-21 in an antigen-based T cell exhaustion model described here suggests that the combination of the two cytokines has a modest effect on reversing the phenotype and function of terminally exhausted CD8+ T cells as shown by the increase in the percentage of TCF-1 positive cells, decrease in the percentage of TOX positive cells, and increase the percentage of polyfunctional cells.
  • These results indicate that the combination of IL-15 and IL-21 robustly augments NK and CD8 T cell activity. The ability to not only boost cytolytic function of naïve and effector cells but to partially rescue the exhausted phenotype of cytotoxic CD8+ T cells is a promising therapeutic approach and addresses the challenges of immuno-oncology.

The poster presentation is available under the Multi-Cytokine Inhibition tab on the Presentations page of the Technology section on the corporate website.

About Multi-Cytokine Platform and Multi-Cytokine Inhibitors EQ101 & EQ302

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 clinical stage, first-in-class, selective, tri-specific inhibitor of IL-2, IL-9, and IL-15 for intravenous and subcutaneous delivery and EQ302, a preclinical stage, first-in-class, selective, bi-specific inhibitor of IL-15 and IL-21 for oral delivery.

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. Itolizumab: a monoclonal antibody that targets the CD6-ALCAM signaling pathway which plays a central role in the modulation of effector T cells that drive a number of immuno-inflammatory diseases; currently under evaluation in a Phase 3 clinical study of patients with acute graft-versus-host disease (aGVHD) and announced positive data from a Phase 1b clinical study of patients with lupus/lupus nephritis in April 2024. Equillium acquired rights to itolizumab through an exclusive partnership with Biocon Limited, who also provides commercial manufacturing for the product. EQ101: a selective tri-specific cytokine inhibitor targeting IL-2, IL-9, and IL-15; recently announced positive results from a Phase 2 proof-of-concept clinical study of patients with alopecia areata. EQ302: an orally delivered, selective bi-specific cytokine inhibitor targeting IL-15 and IL-21 at pre-clinical stage.

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. 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.

Investor Contact Michael Moore Vice President, Investor Relations & Corporate Communications 619-302-4431 ir@equilliumbio.com

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