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%).