Equillium Eyes Q4 Phase I Start for Ulcerative Colitis Drug EQ504

Key Points

• Equillium plans to start a Phase I trial of EQ504 in ulcerative colitis during the fourth quarter. The healthy-volunteer study will assess safety, tolerability, pharmacokinetics and whether the drug activates AhR in colon tissue, with data expected roughly six months after dosing begins.
• EQ504 is designed for targeted delivery to the colon, potentially providing high local drug exposure with lower systemic exposure. The company believes this approach could improve target engagement and tolerability, and plans to update investors after the first subject is dosed.
• Equillium also is developing an inhaled EQ504 formulation for lung diseases and EQ302, an oral IL-15/IL-21-targeting peptide for celiac disease. The company reported $57.2 million in cash and said its current funding is sufficient to complete EQ504’s Phase I study, with a potential additional $20 million financing tranche.

Equillium NASDAQ: EQ Chief Scientific Officer Stephen Connelly outlined the company’s plans to advance its lead programs, including an oral aryl hydrocarbon receptor, or AhR, modulator for ulcerative colitis and an oral bispecific peptide for celiac disease, during a fireside chat.

Connelly said the company, founded in 2017 and public since 2018, has focused on developing therapies based on novel mechanisms for diseases with significant unmet need. Its current pipeline centers on EQ504, an AhR modulator designed for colonic delivery, and EQ302, an oral peptide intended to inhibit both IL-15 and IL-21.

EQ504 Phase I Study Planned for Fourth Quarter

Equillium plans to begin first-subject dosing in a Phase I study of EQ504 during the fourth quarter, Connelly said. The study will be conducted in healthy volunteers and is expected to generate data within roughly six months of initiation.

The company’s primary goals for the single-ascending-dose and multiple-ascending-dose study are to assess safety and tolerability, while secondary measures will include blood and tissue pharmacokinetics and pharmacodynamics. Equillium also plans to evaluate whether the drug activates AhR in colon tissue using biopsies collected through procedures such as sigmoidoscopies or colonoscopies.

“What we really, at a minimum, would want to see is that we can engage AhR in the colon tissues,” Connelly said. The company expects to use induction of CYP1A1, a downstream marker of AhR activation, as its principal biomarker.

Connelly said the company has obtained good manufacturing practice clinical material and has engaged with regulators. A formulation process took about a month to six weeks longer than expected because it involved multiple participants and shipment logistics, he said.

Equillium intends to provide an update after dosing its first subject. That event is also tied to a potential additional $20 million financing tranche from investors, according to Connelly.

Rationale for Local AhR Delivery

Connelly described AhR as a receptor predominantly found in barrier tissues including the gut, lung and skin. The pathway can influence barrier integrity, immune homeostasis and metabolism of foreign compounds, he said.

EQ504 is derived from ITE, which Connelly described as the first naturally occurring AhR modulator and a compound synthesized in the human gut and lungs. He said EQ504 was selected following medicinal chemistry work intended to improve potency, selectivity, solubility and other drug-like properties compared with natural-product-derived AhR compounds.

According to Connelly, Equillium believes a colon-targeted formulation could provide high local exposure in the tissues most relevant to ulcerative colitis while limiting systemic exposure. He said damaged epithelial cells and inflammatory cells in the gut lining are the primary intended targets for the approach.

“By giving the drug directly to the colon, we can get high local and lower systemic,” Connelly said. He added that the company does not expect systemic exposure to be zero, but believes local delivery could support target engagement while potentially improving tolerability.

Connelly pointed to clinical and preclinical evidence supporting AhR modulation, including results involving Indigo naturalis, a complex mixture containing AhR modulators, as well as an AhR-modulating topical treatment in skin disease. He also cited preclinical work showing EQ504 improved barrier integrity and healing in epithelial models and affected T cells and macrophages involved in inflammation and tissue repair.

Lung Formulation and Celiac Program

Beyond the oral formulation, Equillium is developing an inhaled version of EQ504 for potential fibrotic or inflammatory lung diseases. Connelly said the company is assessing inhalation feasibility, lung toxicology and translational data. Potential indications could include chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis and interstitial lung diseases, though timing for an investigational new drug filing for the lung program remains to be determined.

Equillium is also advancing EQ302, an oral bispecific peptide targeting IL-15 and IL-21 for celiac disease. Connelly said both cytokines are overexpressed in about 70% of patients with persistent inflammation, while IL-2 is generally elevated only following gluten exposure.

The company believes an oral therapy that localizes in tissue could offer a different approach from monoclonal antibodies, particularly in reaching damaged villous areas in the intestine. Connelly said Equillium expects to move EQ302 toward the clinic within 12 to 18 months.

Cash Position

Connelly said Equillium reported cash and equivalents of $57.2 million at the end of its most recent quarter. That figure excludes the potential $20 million second financing tranche. He said the company’s current capital position is sufficient to complete the planned Phase I study of EQ504, while additional guidance on later-stage development plans is expected over time.

About Equillium (NASDAQ:EQ)

Equillium, Inc is a clinical-stage biotechnology company focused on developing therapies for severe autoimmune and inflammatory diseases. The company's research is based on modulating immune pathways involved in T-cell activation, inflammation and tissue damage.

Its lead investigational product is itolizumab, an anti-CD6 monoclonal antibody designed to regulate pathogenic T-cell activity. Equillium has evaluated itolizumab in immune-mediated conditions, including acute graft-versus-host disease and other inflammatory disorders.

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