Equillium(US:EQ)2025-11-05 17:00EQ504: A Novel AhR Modulator for Ulcerative Colitis - Equillium, Inc is developing EQ504, a novel aryl hydrocarbon receptor (AhR) modulator for ulcerative colitis [1] - EQ504 is derived from ITE, a naturally-occurring, endogenous, non-toxic AhR modulator synthesized in the gut & lungs, and is a highly potent and selective modulator of AhR [143][144] - EQ504 has a multi-modal mechanism of action in mucosal homeostasis, modulating immune cell responses and promoting barrier function & tissue repair [148][149][150] - In vitro, EQ504 increases the number and function of suppressive Treg cells that inhibit activity of Th1 and Th17 cells and promote tissue homeostasis [156] - In a DSS colitis animal model, EQ504 blocks weight loss and induces anti-inflammatory cytokines in colon tissue [158][160] Clinical Validation and Market Opportunity - Modulation of AhR has been clinically validated in skin diseases, with up to 34% of patients achieving a PGA-Pso score of 0-1 by week 12 in psoriasis and up to 34% of patients achieving a vIGA-AD score of 0-1 by week 8 in atopic dermatitis [134][136] - Phase 2 trials of Indigo Naturalis in ulcerative colitis showed up to 50% of patients achieved clinical remission with total Mayo score ≤ 2, no individual subscore > 1, and up to 27% of treatment refractory patients achieved clinical remission with total Mayo score < 3, no individual subscore > 1 [138] - Studies of ulcerative colitis patients treated with indigo naturalis demonstrate on-target engagement of AhR through increased intestinal CYP1A1 and high levels of clinical remission [142] - In vivo experiments demonstrate localized delivery of EQ504 directly to the colon of rats, results in >25X greater peak exposures in colon tissues versus blood [167] - The US market for ulcerative colitis treatments is approximately $6 billion, with a substantial unmet need for new oral agents in the pre-biologic setting and opportunities in biologic failure patients and combination therapy [172][173]