Data demonstrate colon tissue PDE4/cAMP pathway modulation and sustained active metabolite exposure above IC90 across the dosing interval
Steady-state pharmacokinetic findings provide mechanistic support for previously reported Phase 1b clinical activity
Additional findings support PALI-2108’s potential as a once-daily, gut-targeted oral therapy
Data presented at Digestive Disease Week 2026 – Access the Poster Here
Denver, CO, May 05, 2026 (GLOBE NEWSWIRE) -- Palisade Bio, Inc. (Nasdaq: PALI) (“Palisade” or the “Company”), a clinical-stage biopharmaceutical company developing next-generation, once-daily, oral PDE4 inhibitor prodrugs designed for targeted delivery to the terminal ileum and colon, today announced the presentation of additional Phase 1a/b analyses of PALI-2108, including delayed ileocolonic activation, high tissue-to-plasma exposure, and sustained steady-state concentrations of the active metabolite (PALI-0008) above IC90, at Digestive Disease Week 2026, further characterizing the pharmacokinetic and translational profile of the program.
These findings build on previously reported positive data demonstrating rapid improvements across clinical, histologic, and biomarker endpoints in ulcerative colitis. Additional analyses describe a differentiated pharmacokinetic profile, including steady-state trough concentrations of PALI-0008 relative to IC90 that are consistent with sustained target engagement over the dosing interval.
Additional pharmacokinetic and translational findings show a steady-state pharmacokinetic analyses demonstrated that pre-dose trough concentrations of the active metabolite PALI-0008 exceeded the IC90 threshold and were approximately 20% higher than single-dose Cmax, supporting continuous target inhibition across the dosing interval. The active metabolite exhibited an extended half-life and reached steady state within ~48 hours, supporting once-daily dosing. Tissue-to-plasma exposure ratios of approximately 6-fold further support preferential localization of drug activity to the intestinal mucosa. Treatment with PALI-2108 resulted in colon-selective suppression of key inflammatory and fibrotic pathways, including JAK–STAT, NF-κB, TNF-α, and TGF-β signaling. These transcriptional changes were observed in colonic tissue but not peripheral blood, supporting localized pharmacologic activity. These effects were supported by biomarker changes consistent with PDE4 inhibition, including decreased mucosal PDE4B expression (~71%), increased cAMP (~27%), reductions in lymphocytes (~30–40%), and decreases in fecal calprotectin (~70%). Further, histological improvements were observed across multiple indices, including reductions in Nancy score (−58%), Robarts Histopathology Index (−56%), and Geboes score (−36%).
“These additional pharmacokinetic and translational analyses further characterize the differentiated profile of PALI-2108, which is designed to be selectively bioactivated in the ileum and colon,” said Mitch Jones, President and Chief Medical Officer of Palisade Bio. “We are encouraged by the sustained steady-state trough levels of the active metabolite, PALI-0008, relative to the IC90 threshold, with trough levels exceeding IC90 throughout the dosing interval, a profile that compares favorably to currently approved systemic PDE4 inhibitors. The observed colon-selective pathway modulation further supports our strategy of localized bioactivation to maximize efficacy while minimizing systemic exposure. We believe this differentiated profile strengthens the case for PALI-2108 as a once-daily oral therapy in ulcerative colitis.”
Previously reported Phase 1a/b data demonstrated rapid and consistent improvements across clinical, histologic, and biomarker endpoints. PALI-2108 showed robust pharmacodynamic activity, including increased cAMP and decreased PDE4B expression, along with reductions in inflammatory markers such as fecal calprotectin, hsCRP and lymphocyte counts. These findings were associated with clinical outcomes, with 100% of patients achieving clinical response and 40% achieving clinical remission. Collectively, these findings highlight a differentiated profile characterized by localized drug activation, sustained target inhibition above IC90, and colon-selective pharmacodynamic effects, supporting continued clinical development of PALI-2108 as a next-generation PDE4 inhibitor for inflammatory bowel disease.
The poster titled, “Gut-Targeted PDE4 Inhibition with PALI-2108 Demonstrates Rapid Clinical, Histologic, and Biomarker Improvement in Ulcerative Colitis: Translational Findings from a Phase 1 Study,” can be accessed here.
About Palisade Bio
Palisade Bio, Inc. (Nasdaq: PALI) (“Palisade” or the “Company”) is a clinical-stage biopharmaceutical company advancing a next-generation oral PDE4 inhibitor prodrug designed to improve pharmacology, tolerability and convenience for patients with inflammatory and fibrotic diseases. Through its differentiated prodrug platform and precision pharmacology strategy, Palisade Bio is committed to transforming proven PDE4 biology into better, safer oral therapies for patients living with chronic inflammatory and fibrotic diseases.
The Company’s lead program, PALI-2108, is a once-daily oral PDE4 inhibitor prodrug designed to be selectively bioactivated in the ileum and colon, initiating targeted PDE4 inhibition at sites of disease while enabling systemic distribution of the active drug. PALI-2108 has demonstrated positive results in a Phase 1a and two Phase 1b clinical trials, including studies in ulcerative colitis (UC) and fibrostenotic Crohn’s Disease (FSCD).
Palisade Bio is now advancing towards two Phase 2 clinical studies in UC and Crohn’s disease (CD). 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: the potential mechanisms of action and therapeutic benefits of PALI-2108, dosing levels and timing of PALI-2108 and plans for regulatory submissions. 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 or durability of effect, observed from preclinical or clinical trials 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.
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