Palisade Bio Reports Rapid Clinical, Histologic and New Mechanistic Colon Tissue RNA Sequencing Data Supporting Targeted Activity of PALI-2108 at ECCO 2026

Core Insights - Palisade Bio, Inc. presented new translational data for PALI-2108, a targeted oral PDE4 inhibitor prodrug, at the 21st Congress of the European Crohn's and Colitis Organization (ECCO) in Stockholm, demonstrating localized target engagement and early clinical response within seven days [1][2][10] Group 1: Clinical Findings - In a Phase 1b trial involving patients with moderate-to-severe ulcerative colitis (UC), PALI-2108 achieved a 100% clinical response rate, with 40% of patients reaching clinical remission as measured by the modified Mayo Score [5][9] - The treatment resulted in significant downregulation of inflammatory and fibrosis-associated gene expression programs, including suppression of TNF-α, JAK–STAT, NF-κB, MAPK, and TGF-β pathways [5][6] - Histologic improvements were observed alongside reductions in fecal calprotectin and high-sensitivity C-reactive protein (hsCRP) levels, indicating a decrease in inflammation [5][6] Group 2: Mechanism of Action - PALI-2108 is designed for localized delivery to the terminal ileum and colon, where it is bioactivated by bacterial enzymes, allowing for targeted PDE4 inhibition at sites of inflammation while minimizing systemic exposure [7][9] - The prodrug's pharmacological activity was confirmed through RNA sequencing and pathway analyses, which showed localized suppression of inflammatory signaling networks in colonic tissue, with peripheral immune profiles remaining largely unchanged [4][6] Group 3: Safety and Tolerability - The safety profile of PALI-2108 was encouraging, with no serious adverse events reported among the 89 subjects in the study, supporting its potential as a differentiated treatment option for inflammatory bowel diseases [1][9] - The localized pharmacology of PALI-2108 aims to improve tolerability by reducing common side effects associated with systemic PDE4 inhibitors, such as diarrhea, nausea, and headache [7][8] Group 4: Future Development - Palisade Bio is advancing PALI-2108 into a Phase 2 clinical study to evaluate clinical remission, response, and pharmacodynamic biomarkers over a 12-week period, with plans for an extension phase to assess maintenance of remission [10]