Announcement • May 07
Palisade Bio Inc Reports Additional Phase 1a/b Data Demonstrating Colon-Targeted Exposure And Sustained IC90 Coverage Supporting Once-Daily Dosing In Ulcerative Colitis
Palisade Bio, Inc. 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 targect 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-?B, TNF-a, and TGF-ß 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%). 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.
