Phase 1b translational data demonstrate localized ileocolonic target engagement, suppression of inflammatory and fibrotic gene programs, and early clinical response within seven days
Encouraging safety profile across 89 subjects supports differentiated, colon-targeted PDE4 approach
Translational analyses confirm local suppression of TNF-α, JAK–STAT, NF-κB, MAPK and TGF-β signaling in colon tissue with minimal peripheral immune modulation
Data presented at the 21st Congress of the European Crohn’s and Colitis Organization (ECCO) in Stockholm, Sweden
Carlsbad, CA, Feb. 23, 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 new translational data for PALI-2108 at the 21st Congress of the European Crohn’s and Colitis Organization (ECCO) in Stockholm, Sweden.
The poster, titled “Oral Locally Bioactivated PDE4 Inhibitor Prodrug PALI-2108 Demonstrates Rapid Clinical, Histologic, and Biomarker Improvement in Ulcerative Colitis: Phase 1b Translational Findings,” highlights data showing that PALI-2108 produced measurable clinical response within seven days, improved histologic markers of inflammation in colon tissue, and reduced key inflammatory biomarkers. The data also demonstrates localized pharmacologic activity in the colon, including reduced PDE4B expression and modulation of inflammatory signaling pathways, supporting the intended targeted mechanism of the program. Access the poster here.
Key Highlights
Colon biopsy RNA sequencing revealed:
- Significant downregulation of inflammatory and fibrosis-associated gene expression programs
- Suppression of TNF-α, JAK–STAT, NF-κB, MAPK and TGF-β pathway activity using PROGENy-derived pathway scoring
- Reduced inflammatory cell signatures, including lymphocyte-associated markers, based on cellular deconvolution analyses
- Decreased mucosal PDE4B expression accompanied by increased tissue cAMP levels
Clinical Context:
As previously reported, in the Phase 1b cohort of patients with moderate-to-severe ulcerative colitis (UC) treated for seven days:
- 100% achieved clinical response by modified Mayo Score
- 40% achieved clinical remission by modified Mayo Score
- Histologic improvement and reductions in fecal calprotectin and hsCRP were observed
- Demonstrated localized target engagement in colon tissue with reduced PDE4B expression and increased cAMP
- No UC patient discontinuations (which follows the Company’s earlier findings of no serious adverse events across 84 normal healthy volunteers)
“These mechanistic data provide important molecular support for PALI-2108’s colon-targeted design,” said Mitch Jones, M.D., Ph.D., President and Chief Medical Officer of Palisade Bio. “RNA sequencing and pathway analyses demonstrate suppression of key inflammatory and fibrotic signaling networks directly within colonic tissue, while peripheral immune profiles remain largely unchanged. This localized pharmacology supports our strategy to enhance the therapeutic index of PDE4 inhibition by concentrating activity at the site of disease.”
In the Phase 1b cohort, five adults with moderate-to-severe UC received titrated PALI-2108 for seven days. All patients achieved clinical response, with a subset reaching clinical remission. Improvements were accompanied by reductions in mucosal inflammatory gene expression, fibrosis-associated gene signatures and key inflammatory pathways including JAK-STAT, NF-κB, TNF-α, MAPK, and TGF-β. Colon tissue analyses demonstrated reduced lymphocyte infiltration, decreased neutrophil signatures and broad dampening of inflammatory programs consistent with PDE4 inhibition–mediated elevation of cAMP. Importantly, peripheral blood immune profiles remained largely unchanged, supporting localized pharmacologic activity in the colon.
Dr. Jones added, “We believe the convergence of pharmacokinetics, tissue pharmacodynamics, gene expression modulation and previously reported clinical responses helps to further de-risk the program as we advance PALI-2108 into later-stage development.”
About PALI-2108
PALI-2108 is a once-daily, oral prodrug designed for targeted delivery of PDE4 inhibition to the terminal ileum and colon through local bacterial bioactivation. The prodrug is pharmacologically inactive until it reaches the lower intestine, where bacterial enzymes convert it into the active PDE4 inhibitor at sites of inflammation and fibrosis. This targeted activation strategy prevents absorption in the upper gut, enables sustained local exposure with controlled systemic distribution, and is engineered to reduce peak plasma levels, thereby improving the overall therapeutic index and reducing tolerability limitations such as diarrhea, nausea and headache that have constrained systemic PDE4 inhibitors.
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 prodrugs 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. In a recently reported Phase 1b trial, PALI-2108 achieved a 100% clinical response in the UC cohort, with no serious adverse events, favorable tolerability and pharmacokinetics consistent with localized activation in the lower intestine, low systemic exposure, and controlled release within the GI tract.
Palisade Bio is now advancing towards a Phase 2 clinical study in UC designed to evaluate clinical remission, response and pharmacodynamic biomarkers over 12 weeks, with an extension phase assessing maintenance of remission. In addition, the Company is completing early studies in fibrostenotic crohn’s disease to further characterize PALI-2108’s safety, pharmacology and potential therapeutic benefit across inflammatory bowel disease indications. 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: statements regarding the timing and results of clinical trials, the potential mechanisms of action and therapeutic benefits 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, dosing or durability of effect, observed from preclinical or clinical trials, 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, 2024, filed with the Securities and Exchange Commission (“SEC”) on March 24, 2025, 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.
Investor Relations Contact
JTC Team, LLC
Jenene Thomas
908-824-0775
PALI@jtcir.com
