Palisade Bio Reports Early PALI-2108 Findings Supporting Phase 2 Studies in Ulcerative Colitis and Crohn’s Disease

Key Points

• Palisade Bio presented five research posters on its experimental oral treatment, PALI-2108, at ACG 2026.
• Small, early-stage studies showed improvements in symptoms, intestinal inflammation and tissue measurements in patients with ulcerative colitis and Crohn’s disease.
• Drug-exposure findings support further testing of once-daily dosing.
• Two presentations received ACG Presidential Poster Awards.
• The patient studies included only five people each, lasted seven or 14 days and had no placebo groups. Larger trials are needed to confirm the findings.

Palisade Bio (NASDAQ: PALI) has reported new findings that support continued Phase 2 testing of PALI-2108, its experimental oral treatment for ulcerative colitis and Crohn’s disease.

Presented at the American College of Gastroenterology’s annual meeting in Nashville, the research examined whether the drug reaches intestinal tissue, acts on its intended target and produces early signs of improvement. The results provide a rationale for further development, but do not establish that the treatment is effective.

Ulcerative Colitis Study Shows Early Improvement in Five Patients

Five patients with moderate-to-severe ulcerative colitis received PALI-2108 for seven days in an open-label study, meaning patients and researchers knew which treatment was being given.

All five met the study’s criteria for clinical response, and two achieved clinical remission. The average modified Mayo score, a measure used to assess ulcerative colitis severity, fell by 62.8%.

Intestinal tissue analyses also showed signs of reduced inflammation. Four patients had lower fecal calprotectin, an inflammation marker, and tissue measurements supported activity on the drug’s intended PDE4 target.

These findings support the ongoing Phase 2 ASCENTRA-UC study, which is designed to compare once-daily doses of 15 mg and 30 mg with placebo in approximately 204 patients.

Crohn’s Disease Study Reports Early Changes After 14 Days

A separate study treated five adults with symptomatic fibrostenotic Crohn’s disease affecting the ileum, a section of the small intestine. This form of the disease involves intestinal narrowing associated with scarring.

Patients received PALI-2108 for 14 days. Four were also taking biologic therapies, which makes it harder to isolate PALI-2108’s contribution to the observed changes.

The average endoscopic disease-severity score fell by 47.5%. Two patients met criteria for endoscopic response, and two met criteria for endoscopic remission.

All reported side effects were mild, with no serious adverse events or treatment discontinuations. No nausea, vomiting or diarrhea was reported. However, five patients followed for two weeks cannot establish long-term safety.

Researchers also observed changes in blood markers related to collagen breakdown and tissue remodeling. Those findings warrant further study, but they do not show that PALI-2108 reverses intestinal scarring or narrowing.

Drug-Exposure Findings Support Once-Daily Testing

PALI-2108 is a prodrug: it is designed to be converted into its active form, PALI-0008, by the gut microbiome. The active drug inhibits PDE4, the target being studied for its effects on intestinal inflammation.

In the evaluated Crohn’s disease group, active-drug concentrations in sampled intestinal tissue were approximately seven times higher than peak blood concentrations.

At a 30 mg once-daily dose, blood exposure remained above an estimated level needed for substantial PDE4 inhibition over 24 hours. Together, these findings support further evaluation of once-daily dosing. They do not prove that once-daily treatment will deliver sustained clinical benefits.

Microbiome and Biomarker Research Remains Exploratory

The microbiome analysis found that PALI-2108 was converted into its active form in both healthy volunteers and patients with ulcerative colitis. Researchers detected no statistically significant changes in measured microbiome diversity during seven days of treatment.

Separately, an analysis of approximately 3,000 gene-expression samples from more than 15 studies explored patterns that might help predict treatment response. Those candidate biomarkers still need prospective validation and are not established tools for choosing patients for PALI-2108.

Two of the five presentations received ACG Presidential Poster Awards, a distinction the announcement says goes to approximately 5% of accepted abstracts. The awards recognize the research, not the treatment’s effectiveness.

Investor Takeaway: Encouraging Early Signals, With Phase 2 Still the Key Test

For PALI investors, the announcement connects several elements of the development program: intestinal drug delivery, activity on the intended target and early patient improvements.

The main limitation is the strength of the clinical evidence. Both patient studies were very small, short and lacked placebo comparisons. The larger Phase 2 studies will be the more meaningful test of whether these early findings translate into reliable benefits and an acceptable safety profile.