Palisade Bio Presents Rapid Endoscopic Improvement and New Translational Evidence for PALI-2108 in Inflammatory Bowel Disease at UEG Week 2026

Five-patient Phase 1b Crohn’s disease cohort showed a 47.5% reduction in mean endoscopic disease activity and a 58.8% reduction in mean fecal calprotectin after 14 days

Intestinal exposure and tissue analyses strengthen the rationale for an oral, once-daily therapy targeting the ileum and colon

Phase 2b ASCENTRA-UC study enrolling; Phase 2a Crohn’s disease study being initiated

Denver, CO, Oct. 20, 2026 (GLOBE NEWSWIRE) — Palisade Bio, Inc. (Nasdaq: PALI) (“Palisade” or the “Company”), a clinical-stage biopharmaceutical company developing oral therapies for immune-mediated diseases, announced clinical and translational findings presented in one oral presentation and three moderated posters at United European Gastroenterology (UEG) Week 2026, held October 17–20 in Barcelona, Spain. The findings connect targeted intestinal exposure to PALI-0008, the active metabolite of PALI-2108, with PDE4 target engagement, reduced intestinal inflammation and early clinical activity in ulcerative colitis (UC) and fibrostenotic Crohn’s disease (FSCD).

The new analyses build on previously reported Phase 1b results: a 47.5% reduction in mean endoscopic disease activity after 14 days in five patients with FSCD, and clinical response in all five patients in a separate UC cohort assessed after seven days. Palisade is enrolling the Phase 2b ASCENTRA-UC study and initiating a Phase 2a open-label study in Crohn’s disease.

“The strength of these findings is the connection between drug exposure at the site of disease, biological activity in intestinal tissue and early improvement on endoscopy,” said Mitch Jones, M.D., Ph.D., President and Chief Medical Officer of Palisade Bio. “In patients with longstanding fibrostenotic Crohn’s disease, most of whom were receiving biologic therapy, we observed endoscopic improvement within two weeks alongside reduced intestinal inflammation. Together with our UC findings, these results strengthen our confidence in advancing PALI-2108 as a once-daily oral treatment targeting both the ileum and colon. The exploratory tissue-remodeling signals also provide us with a compelling rationale to investigate its potential beyond inflammation.”

Rapid Endoscopic Improvement in Fibrostenotic Crohn’s Disease

Oral presentation OP003, presented by Florian Rieder, M.D., Cleveland Clinic, describes a Phase 1b open-label study in five patients with symptomatic ileal strictures and a mean disease duration of 15.4 years. Four of five patients were receiving concomitant biologic therapy. Patients received PALI-2108 once daily with food over 14 days, with titration to target doses of 20, 25 or 30 mg.

• Previously reported endoscopic activity: Mean Simple Endoscopic Score for Crohn’s Disease (SES-CD) decreased by 47.5%. Two of five patients (40%) achieved endoscopic response, and two of five (40%) achieved endoscopic remission, defined as an SES-CD of 0–2.
• Reduced intestinal inflammation: Mean fecal calprotectin decreased by 58.8% from baseline. Ileal tissue cAMP increased, consistent with PDE4 target engagement; exploratory analyses identified an inverse association between changes in tissue cAMP and fecal calprotectin.
• Evidence of tissue-level activity: Paired biopsy analyses showed reductions in inflammatory-cell populations. Exploratory single-nucleus RNA analyses identified reduced PDE4D expression in ileal enterocytes in three of four patients with paired sprovamples.
• Exploratory stricture observation: One stricture that could not be traversed by the endoscope at baseline was traversable at Day 14. This single-patient observation does not establish reversal of fibrosis.
• Favorable short-term tolerability: All reported adverse events were mild. No serious adverse events, treatment discontinuations, nausea, vomiting, diarrhea or headache were reported in this five-patient cohort.

Exploratory changes in collagen-degradation and macrophage-associated biomarkers were consistent with potential extracellular matrix remodeling and support further investigation of PALI-2108’s effects on fibrotic disease. These analyses do not establish an antifibrotic clinical benefit.

Early Clinical Activity and Histologic Improvement in Ulcerative Colitis

Moderated poster MP0844 builds on previously reported findings from five patients in the Phase 1b UC cohort, which evaluated titration to 30 mg twice daily. At the Day 7 assessment, all five patients achieved clinical response and two achieved clinical remission. Tissue analyses showed reductions in inflammatory-cell populations and improvements in histologic disease activity, alongside evidence of PDE4 target engagement.

These findings support ASCENTRA-UC, the ongoing Phase 2b study evaluating PALI-2108 at 15 mg and 30 mg once daily versus placebo in approximately 204 patients.

Intestinal Drug Exposure Supports Once-Daily Development

Moderated poster MP0564 further characterizes PALI-2108’s targeted delivery profile. In evaluated FSCD patients, mean intestinal tissue concentrations of active PALI-0008 were approximately 7.3-fold higher than peak plasma concentrations, with exposure demonstrated in the ileum, ascending colon and descending colon. Pharmacokinetic findings also supported sustained plasma exposure above the estimated PDE4 IC90, the concentration associated with 90% inhibition in vitro, over 24 hours at 30 mg once daily.

Together, these findings support the development of a once-daily oral therapy designed to concentrate PDE4 activity in intestinal tissue while providing sustained systemic exposure with a more gradual rise in plasma drug concentrations.

Transcriptomic Analyses Support Biomarker Development

Moderated poster MP0845 describes an exploratory analysis of approximately 3,000 transcriptomic samples from more than 15 studies. Composite signatures incorporating PDE4/cAMP signaling and inflammatory pathways improved separation of responder and non-responder phenotypes compared with PDE4 gene expression alone. The work supports further investigation of biomarkers that may help characterize treatment response; prospective predictive utility for PALI-2108 has not been established.

The UC and FSCD clinical findings are exploratory and derive from small, short-duration, open-label cohorts without placebo controls. They require confirmation in larger controlled studies. The studies do not establish comparative efficacy or safety, durable benefit, or reversal of intestinal fibrosis.

The presentations are available on the Publications page of the Company’s website.

About PALI-2108

PALI-2108 is an investigational oral PDE4 inhibitor prodrug designed for localized bioactivation in the terminal ileum and colon and being developed for once-daily dosing. Its active metabolite, PALI-0008, inhibits PDE4, increasing intracellular cAMP to modulate inflammatory signaling. Phase 1 studies have provided evidence of intestinal exposure, target engagement, favorable short-term tolerability and early clinical activity, supporting Phase 2 development in UC and Crohn’s disease. PALI-2108 has not been approved for any indication.

About Palisade Bio

Palisade Bio is a clinical-stage biopharmaceutical company developing oral therapies for immune-mediated diseases. Its lead program, PALI-2108, is advancing through Phase 2 development in inflammatory bowel disease.

For more information, please go to www.palisadebio.com.

Forward Looking Statements

Any statements contained in this communication that are not statements of historical fact may be deemed to be forward-looking statements for purposes of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include but are not limited to: implied or express statements regarding the pharmacological properties, safety, tolerability, clinical response and efficacy, and therapeutic potential of PALI-2108, dosing levels and timing of key PALI-2108 development milestones such as regulatory submissions and approvals, trial enrollments and commencements and efficacy readouts, and the Company’s expected cash runway. These forward-looking statements are based on the Company’s current expectations. Forward-looking statements involve risks and uncertainties. Important factors that could cause actual results to differ materially from those reflected in the Company’s forward-looking statements include, among others, the timing of enrollment, commencement and completion of the Company’s clinical trials; the Company’s reliance on PALI-2108, and its early stage of clinical development; the risk that prior results, such as signals of safety, clinical response and efficacy, dosing, durability of effect or pharmacological properties, observed from preclinical or clinical trials (such as our Phase 1b findings) with a limited number of patients, will not be replicated or will not continue in ongoing or future studies or clinical trials involving the Company’s product candidates in clinical trials focused on the same or different indications; and other factors that are described in the “Risk Factors” and “Management’s Discussion and Analysis of Financial Condition and Results of Operations” sections of the Company’s Annual Report on Form 10-K for the fiscal year ended December 31, 2025, filed with the Securities and Exchange Commission (“SEC”) on March 20, 2026, and the Quarterly Reports on Form 10-Q or other SEC filings that are filed thereafter. Investors are cautioned not to put undue reliance on these forward-looking statements. These forward-looking statements speak only as of the date hereof, and the Company expressly disclaims any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in the Company’s expectations with regard thereto or any change in events, conditions or circumstances on which any such statements are based, except as required by law.

Investor Relations Contact
JTC Team, LLC
Jenene Thomas
908-824-0775
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