Phase 1 study evaluating safety, tolerability and PK/PD after single and multiple ascending doses in healthy volunteers and biological activity in subjects with celiac disease

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 it has initiated a Phase 1 study of EQ102 in healthy volunteers, completed dosing of the initial cohort of eight study participants and begun dosing the second cohort.

The single ascending dose/multiple ascending dose (SAD/MAD) study is a randomized, double-blind, placebo-controlled study of EQ102 administered subcutaneously as single or multiple doses in up to 64 healthy volunteers. The primary endpoint of the study is to assess the safety and tolerability of EQ102 with secondary endpoints to assess pharmacokinetic and pharmacodynamic (PK/PD) changes. Following the SAD/MAD portion of this study Equillium plans to evaluate the biological activity of EQ102 in subjects with celiac disease.

“This marks a major milestone as the first human study of EQ102, a therapeutic candidate generated de novo from our multi-cytokine inhibitor platform,” said Bruce Steel, chief executive officer at Equillium. “EQ102 inhibits the natural biological synergy of cytokines IL-15 and IL-21 that drive cytotoxic T cell responses in gastrointestinal inflammation. We believe this may be an optimal approach to treating patients with celiac disease, and we look forward to reporting initial clinical data from this study next year.”

“Patients with celiac disease are unfortunately still without an effective therapy to treat their debilitating symptoms and it remains one of the most underserved conditions globally,” said Bana Jabri, M.D., Ph.D., professor of medicine, vice-chair for research in the Department of Medicine at the University of Chicago School of Medicine, and director of research at the University of Chicago Celiac Disease Center. “There is strong evidence that increased levels of the cytokines IL-15 and IL-21 synergize to promote cytotoxic activity of immune cells leading to inflammation and villous atrophy in intestinal tissues of patients with celiac disease. I’m encouraged by the strong pre-clinical and translational data for EQ102 and believe this novel approach and dual-targeting of IL-15 and IL-21 is very well aligned to treat gastrointestinal inflammation in celiac disease and look forward to seeing results from this study.”

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 the Phase 1 Study of EQ102

This is a Phase 1 randomized, double-blind, placebo-controlled study of EQ102 administered subcutaneously as single or multiple doses in up to 64 normal healthy volunteers. In Part A, healthy volunteers will be enrolled and randomized to five cohorts (n=8 per cohort) to receive single ascending doses of EQ102 or placebo. In Part B, healthy volunteers will be enrolled and randomized to three cohorts (n=8 per cohort) to receive multiple ascending doses (MAD) of EQ102 or placebo. The starting dose in Part A will be 50mg with five ascending dose levels planned up to 1,000mg. In Part B, up to three dose levels will be evaluated in healthy volunteers, where the starting dose will be based on safety and pharmacokinetic data from Part A. The primary endpoint of the study is to assess the safety and tolerability of EQ102 after single and multiple ascending subcutaneous doses. Secondary endpoints include the assessment of pharmacokinetic/pharmacodynamic changes after single and multiple ascending doses. Following the MAD portion of this study, Part C of the study will evaluate the biological activity of EQ102 in subjects with celiac disease.

About Celiac Disease

Celiac Disease (CeD), with an estimated global incidence of over 50 million patients, is a chronic inflammatory intestinal disorder caused by an inappropriate immune response to the dietary intake of gluten. It occurs selectively in individuals expressing human leukocyte antigen (HLA)-DQ2 or HLA-DQ8, and results in a mucosal inflammatory response in the intestine. The loss of mucosal integrity in CeD is associated with a high burden of illness resulting from a large number of intestinal and extra-intestinal disease manifestations. Currently, there are no approved treatments and a strict adherence to a gluten-free diet is the only approach for CeD patients to manage the disease. A full recovery is often observed in pediatric CeD patients, but greater than 40% of adult CeD patients maintain histological abnormalities following complete removal of dietary gluten. A significant body of evidence implicates the roles of IL-15 and IL-21 in the pathoetiology of CeD.

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, 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.

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 is a first-in-class tri-specific cytokine inhibitor that selectively targets IL-2, IL-9, and IL-15. Equillium expects to begin enrolling patients in an alopecia areata Phase 2 study of EQ101 in the fourth quarter of 2022. EQ102 is a bi-specific cytokine inhibitor that selectively targets IL-15 and IL-21. Equillium is currently enrolling patients in a Phase 1 study of EQ102, including healthy volunteers and celiac disease patients.

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.

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