Executives from Equillium (NASDAQ:EQ) outlined the scientific rationale and near-term development plans for its lead program, EQ504, during a recent fireside chat focused on immunology and inflammatory bowel disease (IBD).
Positioning EQ504 in ulcerative colitis
Company representatives described ulcerative colitis as a disease driven by three intertwined factors: immune dysregulation, impaired barrier function, and reduced ability of mucosal tissues to heal. They noted that more than a dozen approved therapies primarily target immune modulation, but clinical remission rates have remained “30%-ish,” with mucosal healing identified as a key bottleneck to achieving remission.
AhR as a target and how EQ504 differs
Speakers emphasized that AhR is a well-characterized receptor expressed in barrier tissues including skin, gut, lung, eye, and other epithelial surfaces. They described it as a “xenosensor” that translates chemical signals into biological responses, including detoxification programs and tissue immune homeostasis. They pointed to several forms of validation:
- Genetic and translational evidence: AhR knockout models lose barrier homeostasis and develop inflammation in tissues such as the skin, lung, and gastrointestinal tract.
- Clinical examples: Tapinarof (VTAMA), an AhR modulator used topically in inflammatory skin diseases, shows target engagement through CYP1A1 induction along with improvements in inflammatory signals and barrier function.
- Botanical data in ulcerative colitis: Indigo Naturalis, described as enriched in indirubin (a potent but “not selective” AhR modulator), has been tested in multiple phase II studies and was cited as achieving clinical remission rates of 40%–50%, with strong mucosal healing outcomes. In those studies, investigators observed AhR pathway activation in colonic mucosa, including CYP1A1 and increases in IL-22, a cytokine tied to protective mucosal function.
Management also discussed why relatively few AhR modulators have advanced in IBD. They highlighted two main drug development hurdles: identifying molecules with the right potency and selectivity profile, and delivering them to the target tissues. They contrasted pollutant-derived ligands, which can preferentially induce detoxification pathways, with compounds designed to produce an immunomodulatory profile without inherent toxicities.
Equillium said EQ504 is derived from ITE, which it called a “gold standard” selective AhR modulator, and described EQ504 as a more drug-like analog that is potent, selective, binds to relevant barrier tissues, and is rapidly cleared. Executives also referenced activity in the broader field, including past work at Takeda and a portfolio of structurally designed AhR agonists at Eli Lilly, while noting ongoing challenges in achieving the desired drug-like properties.
Development status: formulation as the pacing item
Equillium said key IND-enabling studies have been completed, and that the main rate-limiting step before dosing healthy volunteers is finalizing the colon-targeted formulation. The company described an enteric-coated system using mini-tablets or spheres designed to dissolve in the colon and distribute drug throughout the colon to increase local exposure while reducing systemic exposure.
The team said it is working with a partner described as a global leader in the technology and noted that similar delivery approaches are already used in ulcerative colitis therapies. For the initial clinical work, Equillium expects to conduct the first-in-human study in Australia, citing a faster regulatory turnaround, rather than submitting a U.S. IND for that initial work.
Phase 1 design, biomarkers, and timing
Executives characterized the planned study as a typical single-ascending dose (SAD) and multiple-ascending dose (MAD) trial in normal healthy volunteers. They said the company plans to use flexible sigmoidoscopy and colon biopsies to measure tissue exposure and pharmacodynamic effects directly in colonic tissue—an approach they contrasted with relying only on systemic drug levels as a proxy for colon exposure.
On biomarkers, management said CYP1A1 is expected to be a consistent target-engagement marker for AhR activation, and IL-22 is among the markers of interest for mucosal protection. They indicated IL-22 changes would be more likely observed after multiple dosing rather than in single-dose cohorts. Equillium said it is consulting its advisory board on whether to add patient cohorts (a potential “1B/1C” component) versus moving from phase 1 directly to a phase 2 patient study.
The company said it is tracking to initiate the phase 1 study mid-year, with SAD/MAD data expected in the first half of 2027.
Cash runway and longer-term opportunities
Equillium also discussed its financing and runway. Management referenced an August financing totaling $50 million, comprised of $30 million upfront and a second $20 million tranche to be triggered at the start of the first clinical study. The company said its public cash runway guidance reflects only the $30 million received and extends “towards the end of 2027,” while the additional tranche would extend runway “well into” the 2027–2028 timeframe. Executives said this should fund the SAD/MAD program and, in their view, likely support progression to some patient-level data.
Beyond ulcerative colitis, the team highlighted potential expansion opportunities for AhR modulation in lung diseases, noting AhR’s importance in lung tissue and suggesting EQ504’s water solubility could support potential nebulized delivery. They also mentioned the possibility of adapting gastrointestinal delivery for Crohn’s disease, while noting that Indigo Naturalis historically did not show strength in Crohn’s and that distribution to different regions of the GI tract could be a contributing factor.
About Equillium (NASDAQ:EQ)
Equillium, Inc (NASDAQ: EQ) is a clinical-stage biopharmaceutical company focused on developing novel immunotherapies to treat severe autoimmune diseases and prevent organ transplant rejection. The company’s lead therapeutic candidate, EQ001 (itolizumab), is a humanized monoclonal antibody that modulates T-cell activation by targeting the CD6 receptor. Equillium’s pipeline also includes additional biologic candidates aimed at addressing indications such as acute graft-versus-host disease (GVHD) and lupus nephritis.
Founded in 2015 and headquartered in La Jolla, California, Equillium in-licensed itolizumab from Biocon Limited, leveraging the antibody’s established safety profile in earlier clinical studies.
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