Five presentations connect targeted intestinal exposure and sustained systemic drug exposure with PDE4 target engagement and early clinical activity, supporting ongoing Phase 2 development
Two presentations selected for ACG Presidential Poster Awards, a distinction received by approximately 5% of accepted abstracts
Microbiome and transcriptomic analyses support the delivery platform and a potential precision medicine approach
Denver, CO, Oct. 12, 2026 (GLOBE NEWSWIRE) -- Palisade Bio, Inc. (Nasdaq: PALI) (“Palisade” or the “Company”), a clinical-stage biopharmaceutical company developing next-generation oral therapies for immune-mediated diseases, today announced clinical and translational findings featured in five poster presentations at the American College of Gastroenterology (ACG) 2026 Annual Scientific Meeting in Nashville, Tennessee. The findings strengthen the scientific rationale for the Company’s ongoing Phase 2 development of PALI-2108, its investigational oral, locally activated PDE4 inhibitor prodrug, in ulcerative colitis (UC) and Crohn’s disease (CD).
“These findings connect the key elements of our development strategy: delivering active drug to diseased intestinal tissue, engaging PDE4, and observing early clinical activity alongside reductions in inflammation,” said Mitch Jones, M.D., Ph.D., President and Chief Medical Officer of Palisade Bio. “The tissue analyses strengthen the mechanistic foundation for the clinical signals observed in UC and fibrostenotic Crohn’s disease, while our microbiome and biomarker work supports the delivery platform and a potential path toward more informed patient selection. As we advance our Phase 2 programs, the two Presidential Poster Awards are meaningful recognition of the work of our investigators and collaborators.”
Ulcerative Colitis Findings Link Target Engagement to Early Clinical and Histologic Improvement
Poster P3504 — ACG Presidential Poster Award: “The Microbiome-Activated Phosphodiesterase (PDE)-4 Inhibitor, PALI-2108 Leads to Rapid Clinical and Histologic Improvement in Moderate-to-Severe Ulcerative Colitis: A Phase1a/1b Study”
Five patients with moderate-to-severe UC received open-label PALI-2108 for seven days, including a five-day titration to 30 mg twice daily. Findings included:
- Early clinical activity: All five patients achieved clinical response and two achieved clinical remission. The poster reported a 62.8% mean reduction in modified Mayo score, alongside improvements in the Nancy, Robarts, and Geboes histologic indices.
- Evidence of target engagement: Colonic tissue cAMP increased in four of five patients, and PDE4B expression decreased in all five. Fecal calprotectin decreased in four of five patients.
- Tissue evidence of reduced inflammation: PathAI-enabled quantitative digital pathology identified reductions in tissue lymphocytes and other inflammatory-cell populations, together with structural changes consistent with early mucosal improvement, including increased normal epithelium and goblet cell mucin and reduced ulceration.
These findings provide clinical and mechanistic support for the ongoing Phase 2 ASCENTRA-UC study, which is designed to evaluate once-daily PALI-2108 at 15 mg and 30 mg versus placebo in approximately 204 patients. Steady-state pharmacokinetic data from healthy volunteers receiving 15 mg, 30 mg and 45 mg once daily demonstrated sustained exposure to PALI-0008, the active metabolite of PALI-2108, providing additional pharmacologic support for dose selection in the Phase 2 program.
Crohn’s Disease Findings Show Early Endoscopic Activity and Changes in Tissue Remodeling Biomarkers
Poster P3611: “Gut-Targeted Inhibition of Phosphodiesterase 4 with PALI-2108 Demonstrates Early Endoscopic and Biomarker Improvements in Fibrostenotic Crohn’s Disease: Results from a Phase 1b Study”
Five adults with symptomatic ileal fibrostenotic Crohn’s disease (FSCD) received open-label PALI-2108 once daily with food for 14 days, including a 10-day titration to target doses of 20, 25, or 30 mg. Four of five patients were receiving concomitant biologic therapy. Findings included:
- Favorable short-term tolerability: All reported adverse events were mild, with no serious adverse events or treatment discontinuations. No nausea, vomiting, or diarrhea were reported.
- Early endoscopic activity: A 47.5% mean reduction in the Simple Endoscopic Score for Crohn’s Disease (SES-CD), with two of five patients achieving endoscopic response and two of five achieving endoscopic remission after 14 days.
- Evidence of local pharmacologic activity: Increased ileal tissue cAMP and reduced fecal calprotectin were accompanied by reductions in inflammatory-cell densities in paired intestinal biopsies.
- Exploratory tissue-remodeling signals: Plasma biomarker changes were consistent with increased collagen degradation and changes in markers associated with macrophage activation. These findings support further evaluation of potential effects on extracellular matrix remodeling; they do not establish reversal of intestinal fibrosis or strictures.
The findings support continued evaluation in the Company’s Phase 2 Crohn’s disease program. The UC and FSCD patient cohorts were small, short-duration, open-label studies without placebo control; their clinical and translational findings require confirmation in larger studies.
Intestinal Exposure and Sustained Pharmacokinetics Support Once-Daily Development
Poster P3413 — ACG Presidential Poster Award: “PALI-2108, a Next-Generation Oral PDE4 Inhibitor Prodrug, Demonstrates Localized Ileocolonic Exposure with Favorable Tolerability in IBD”
Analyses across the Phase 1a/b program support the pharmacologic rationale for targeted intestinal delivery and once-daily dosing:
- Targeted intestinal exposure: Concentrations of PALI-0008, the active metabolite of PALI-2108, in sampled ileal and colonic tissue were approximately sevenfold higher than peak plasma concentrations in the evaluated FSCD cohort.
- Sustained exposure: At 30 mg once daily, the poster reported PALI-0008 plasma exposure above the estimated PDE4 IC90 over 24 hours, supporting continued once-daily development.
- Exploratory pharmacokinetic comparisons: The pooled 30 mg once-daily cohort showed lower trough-concentration variability than published apremilast and mufemilast datasets, alongside comparisons of daily exposure normalized to PDE4 inhibitory potency. These comparisons were based on small cohorts and differing study populations and conditions and do not establish comparative clinical efficacy or safety.
Microbiome Findings Support Prodrug Activation Without Significant Short-Term Diversity Changes
Poster P3412: “Microbiome Beta-Glucuronidase Activity Does Not Limit Bioconversion or Pharmacokinetic Consistency of the Colon-Targeted PDE4 Prodrug PALI-2108 in Ulcerative Colitis”
Because PALI-2108 relies on the gut microbiome for activation, the analysis examined whether differences in microbiome composition could affect its conversion to PALI-0008, the active drug. Findings included:
- Evidence of microbiome activation: PALI-2108 was converted to PALI-0008 in both healthy volunteers and patients with UC, supporting microbiome-mediated activation in the evaluated cohorts.
- Comparability of functional features: Beta-glucuronidase-associated functional features were comparable between evaluated healthy volunteers and patients with UC and remained stable over seven days of treatment.
- Consistency in microbiome diversity: No statistically significant changes in measured alpha or beta microbiome diversity were detected in patients with UC over seven days. These short-term findings support further evaluation of the platform’s compatibility with the intestinal microbiome.
Exploratory Transcriptomic Research Supports a Potential Precision Medicine Approach
Poster P3505: “Development of Mucosal Transcriptomic Signatures to Predict Response to the Microbiome-Activated Phosphodiesterase (PDE)-4 Inhibitor PALI-2108 in Ulcerative Colitis”
An analysis integrating approximately 3,000 transcriptomic samples from more than 15 studies combined UC disease biology with PDE4/cAMP pathway activity to develop candidate treatment-response signatures. Findings included:
- Potential for patient stratification: Exploratory signatures showed preliminary discrimination between responder and non-responder phenotypes, supporting further evaluation of a mechanistically informed approach to patient stratification.
- Integration of inflammatory signaling into framework: The framework integrated inflammatory signaling and PDE4-associated pathways, with additional analyses of fibrosis-related transcriptional activity.
- Potential treatment-response biomarker: The findings support continued prospective validation of a potential treatment-response biomarker; the signatures are not established clinical tools for selecting patients for PALI-2108 treatment.
About the ACG Presidential Poster Awards
Posters P3413 and P3504 were selected for ACG Presidential Poster Awards. Recipients are selected by the ACG Abstract Selection Committee based on scores and scientific merit. Approximately 5% of accepted abstracts receive the distinction each year.
About PALI-2108
PALI-2108 is an investigational oral, locally activated PDE4 inhibitor prodrug designed for targeted 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 in healthy volunteers and patients with UC or FSCD have provided evidence of intestinal exposure, target engagement, favorable short-term tolerability, and early clinical activity, supporting continued Phase 2 development. PALI-2108 has not been approved for any indication.
About Palisade Bio
Palisade Bio is a clinical-stage biopharmaceutical company developing next-generation oral therapies for immune-mediated diseases. Its lead program, PALI-2108, is advancing in inflammatory bowel disease, with Phase 2 studies in ulcerative colitis and Crohn’s disease. For more information, please visit 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
