Palisade Bio Presents Rapid Endoscopic Improvement and New Translational Evidence for PALI-2108 in Inflammatory Bowel Disease at UEG Week 2026
Intestinal exposure findings support once-daily development, while the exploratory clinical results require confirmation in larger controlled studies.
Sentiment and the balance of points
Rhea-AI Sentiment reads the wording of the document, how positive or negative its language is on a 1 to 5 scale. The balance of points shown with the takes weighs what the document actually discloses, so the two can disagree, for example when a trial that missed its main goal is described in upbeat language.
Rhea-AI Summary
Palisade Bio (PALI) presented early PALI-2108 clinical results and intestinal tissue analyses in inflammatory bowel disease at UEG Week 2026. In five Phase 1b fibrostenotic Crohn’s disease patients, mean endoscopic disease activity fell 47.5% and mean fecal calprotectin, an intestinal inflammation marker, fell 58.8% after 14 days. Two patients achieved endoscopic response and two achieved endoscopic remission. All reported adverse events were mild.
In a separate five-patient ulcerative colitis cohort, all achieved clinical response and two achieved remission at Day 7. Tissue analyses showed biological activity. Both cohorts were small, short-duration and open-label, without placebo controls; results require confirmation and do not establish reversal of fibrosis. Palisade is enrolling the approximately 204-patient Phase 2b ASCENTRA-UC study and initiating an open-label Phase 2a Crohn’s disease study.
How this balance works
Rhea-AI gives every point it takes from this document a weight. Minor counts 1, Moderate 3 and Major 9, so one Major point outweighs several Minor ones. The bar adds up the weights on each side, and when neither side holds more than 65% of the total the balance reads Mixed.
It reads the document as published, with the same rules for every company, and it does not look at what the market expected or at how the stock traded, so a point can be objectively good on a day the stock falls.
Rhea-AI Sentiment measures something else, the tone of the wording.
Hollow bars mark forward-looking points. How the balance works
Positive
- Moderate pointCrohn’s mean endoscopic disease activity decreased 47.5% after 14 days in five Phase 1b patients.
- Moderate pointCrohn’s mean fecal calprotectin decreased 58.8% from baseline, indicating reduced intestinal inflammation.
- Moderate pointUC clinical response occurred in all five patients; two achieved clinical remission at Day 7.
- Moderate pointASCENTRA-UC is enrolling approximately 204 patients, testing 15 mg and 30 mg once daily versus placebo.
- Moderate point. Forward-looking: it has not happened yet and may not happen.Crohn’s development is advancing with initiation of an open-label Phase 2a study.
8 minor points
- Minor pointCrohn’s endoscopic response and remission each occurred in two of five patients (40%).
- Minor pointCrohn’s tolerability findings included only mild adverse events, with no serious events or treatment discontinuations.
- Minor pointCrohn’s cohort reported no nausea, vomiting, diarrhea or headache during the study.
- Minor pointUC tissue analyses showed improved microscopic disease activity and reduced inflammatory-cell populations.
- Minor pointCrohn’s tissue analyses showed PDE4 target engagement and reductions in inflammatory-cell populations.
- Minor pointIntestinal active-metabolite concentrations averaged approximately 7.3-fold higher than peak plasma concentrations in evaluated Crohn’s patients.
- Minor pointDrug exposure at 30 mg once daily remained above the estimated laboratory-derived 90% PDE4 inhibition concentration over 24 hours.
- Minor pointExploratory composite biomarker signatures improved responder/non-responder separation compared with PDE4 gene expression alone.
Negative
- Minor pointClinical findings derive from five-patient, short-duration, open-label cohorts without placebo controls and require larger controlled studies.
- Minor pointCrohn’s cohort included four of five patients receiving concomitant biologic therapy.
- Minor pointStudies do not establish comparative efficacy or safety, or durable benefit.
- Minor pointExploratory stricture and tissue-remodeling observations do not establish fibrosis reversal or an antifibrotic clinical benefit.
- Minor pointExploratory biomarkers have no established prospective predictive utility for PALI-2108.
News Explained
Palisade reports mean intestinal concentrations of active PALI-0008 higher than peak plasma levels and plasma exposure above an estimated in-vitro PDE4 inhibition threshold for 24 hours at 30 mg once daily, supporting the dosing design but not establishing clinical benefit.
Key Figures
- Mean endoscopic disease activity reduction
- 47.5%
- Five-patient Phase 1b FSCD cohort after 14 days
- Mean fecal calprotectin reduction
- 58.8%
- Five-patient Phase 1b FSCD cohort from baseline
- Endoscopic response
- 2 of 5 patients (40%)
- Phase 1b FSCD cohort
- Endoscopic remission
- 2 of 5 patients (40%)
- Phase 1b FSCD cohort; remission defined as SES-CD 0–2
- Clinical response
- All 5 patients
- Phase 1b UC cohort at Day 7
- Intestinal tissue concentration of PALI-0008
- Approximately 7.3-fold higher than peak plasma concentration
- Evaluated FSCD patients
- Plasma exposure above estimated PDE4 IC90
- Over 24 hours at 30 mg once daily
- Pharmacokinetic findings
- ASCENTRA-UC study size
- Approximately 204 patients
- Phase 2b study
Historical Context
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Five FSCD patients had a 47.5% mean endoscopic-score reduction; all five UC patients responded.
24h Move is the share-price change in the day after each event; other market factors may also have contributed.
Key Terms
pde4 medical
fecal calprotectin medical
ses-cd medical
camp medical
AI-generated analysis. How Rhea-AI works. Not financial advice.
Five-patient Phase 1b Crohn’s disease cohort showed a
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
“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
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
PALI@jtcir.com
FAQ
AI-generated questions and answers. How Rhea-AI works. Not financial advice.
What did Palisade Bio’s PALI-2108 Crohn’s disease study show?
In five Phase 1b patients, mean endoscopic disease activity decreased 47.5% and mean fecal calprotectin decreased 58.8% after 14 days. Two patients achieved endoscopic response and two achieved endoscopic remission. The small, open-label study had no placebo control and requires confirmation in larger controlled studies.
What is Palisade Bio testing in the ASCENTRA-UC trial?
The enrolling Phase 2b ASCENTRA-UC study evaluates PALI-2108 at 15 mg and 30 mg once daily versus placebo in approximately 204 patients. The earlier five-patient Phase 1b UC cohort evaluated titration to 30 mg twice daily, with all five achieving clinical response and two achieving clinical remission at Day 7.
Did PALI-2108 reverse intestinal fibrosis in Palisade Bio’s Crohn’s study?
The study did not establish reversal of intestinal fibrosis. One stricture that an endoscope could not pass at baseline was passable at Day 14. This single-patient observation and exploratory tissue-remodeling biomarkers do not establish an antifibrotic clinical benefit.
What supports once-daily development of Palisade Bio’s PALI-2108?
Intestinal tissue exposure and sustained plasma exposure support once-daily development. In evaluated Crohn’s patients, mean intestinal concentrations of active metabolite PALI-0008 were approximately 7.3-fold higher than peak plasma concentrations. At 30 mg once daily, plasma exposure remained above the estimated concentration associated with 90% PDE4 inhibition in laboratory testing over 24 hours.