Palisade Bio Inc. (PALI), a clinical-stage biopharmaceutical company, presented findings on PALI-2108 covering both ulcerative colitis and Crohn's disease — drawn from clinical and translational work — at the American College of Gastroenterology's 2026 Annual Scientific Meeting. Across all five presentations, the drug's behaviour in the intestinal tract, its biological mechanisms, early responses observed in patients, and markers that may predict treatment outcomes each received dedicated attention.
Both ulcerative colitis and Crohn's disease fall under the umbrella of inflammatory bowel disease, a group of long-term conditions in which the body's immune response triggers persistent irritation along the digestive tract. Taken orally once a day, PALI-2108 is a prodrug under investigation engineered to become active specifically within the terminal ileum and colon after administration. PALI-0008, the compound's primary breakdown product, targets and inhibits the PDE4 enzyme — a mechanism designed to reduce the body's inflammatory messaging pathways.
A Phase 1a/1b trial enrolled five participants diagnosed with moderate-to-severe ulcerative colitis in a seven-day treatment window with PALI-2108. Of the five participants, two reached clinical remission while the remaining three recorded a clinical response. Averaged across participants, the modified Mayo score dropped by 62.8 percentage points from its baseline value.
Tissue samples showed measurable gains at the histological level, cyclic AMP concentrations in the colon rose, and markers tied to inflammation — fecal calprotectin among them — declined. A distinct Phase 1b arm of the trial enrolled five adults diagnosed with fibrostenotic Crohn's disease, who underwent PALI-2108 treatment across a 14-day period.
Endoscopic measurements from the trial recorded a mean drop of 47.5% on the Simple Endoscopic Score for Crohn's Disease scale, with two participants meeting the threshold for endoscopic response and a further two reaching the benchmark for endoscopic remission. Every side effect logged across the study fell into the low-end category, with no participant withdrawing from treatment and no event reaching a threshold that warranted classification as a health concern.
Tissue samples drawn from the intestinal wall of participants in the Crohn's disease cohort contained active-metabolite levels running roughly sevenfold above the highest plasma concentrations recorded during the study. Drug concentrations recorded at the 30 mg once-daily dose held above the PDE4 IC90 benchmark throughout the full 24-hour window, a finding the company indicated lends weight to continued investigation of that dosing schedule.
In both healthy volunteers and people living with ulcerative colitis, PALI-2108 underwent conversion to its pharmacologically active form, with gut microbiome diversity measurements showing no statistically meaningful shift across the seven-day observation window. Exploratory transcriptomic work, drawing on roughly 3,000 tissue samples pooled across more than 15 independent studies, surfaced potential signatures linked to treatment response — findings that still await confirmation through dedicated validation efforts.
Data gathered at this stage of the Phase 1 trial remain early-stage: each of the two patient groups enrolled just five people, the design was open-label throughout, and no placebo arm was built into either cohort. The company noted that those findings point toward the need for further study, and that validation through larger controlled trials represents a necessary next step.
Two Phase 2 clinical programmes are currently under way for PALI-2108. The ASCENTRA-UC trial is enrolling approximately 204 participants and compares once-daily oral doses of 15 mg and 30 mg against a placebo, with headline efficacy data anticipated in the latter half of 2027. The ASCENTRA-CD trial is enrolling around 60 people living with moderate-to-severe Crohn's disease, with key efficacy data anticipated from analysis in the opening months of 2028.
