Denver, CO — May 5, 2026 — Leads & Copy — Palisade Bio, Inc. (Nasdaq: PALI) presented additional Phase 1a/b analyses of PALI-2108 at Digestive Disease Week 2026, showcasing the drug’s delayed ileocolonic activation, high tissue-to-plasma exposure, and sustained steady-state concentrations of the active metabolite (PALI-0008) above IC90.
The data further characterize the pharmacokinetic and translational profile of the program, according to the company.
The 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.
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%).
Mitch Jones, President and Chief Medical Officer of Palisade Bio, said the analyses further characterize the differentiated profile of PALI-2108, which is designed to be selectively bioactivated in the ileum and colon.
Jones added that the company is 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 the strategy of localized bioactivation to maximize efficacy while minimizing systemic exposure, Jones said. He believes 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.
Palisade Bio, Inc. 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. 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).
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.
Source: Palisade Bio
