Palisade Bio, Inc. Reports Rapid Clinical And Histologic Improvements With New Colon Tissue RNA-Seq Evidence Showing Targeted Activity Of PALI-2108 At The 21st Congress Of The European Crohn’s & Colitis Organization 2026

Palisade Bio, Inc. announced new translational data for its investigational therapy PALI-2108, presented at the 21st Congress of the European Crohn’s and Colitis Organization in Stockholm. The company is developing next-generation, once-daily oral PDE4 inhibitor prodrugs designed to release their active components specifically in the terminal ileum and colon. 

According to the presentation, PALI-2108 demonstrated rapid clinical improvement, meaningful histologic changes in colon tissue, and reductions in key inflammatory biomarkers in patients with ulcerative colitis after only seven days of treatment. The data also showed clear evidence of localized pharmacologic activity in the colon, including decreased PDE4B expression and modulation of inflammatory pathways that align with the drug’s intended mechanism.

The poster highlighted extensive findings from RNA sequencing of colon biopsies. These analyses showed strong downregulation of genes associated with inflammation and fibrosis, along with suppressed activity in major inflammatory pathways such as TNF-α, JAK-STAT, NF-κB, MAPK and TGF-β. Cellular deconvolution further revealed reduced signatures of inflammatory cell types, particularly lymphocyte-associated markers. The tissue also exhibited decreased PDE4B expression and increased cAMP levels, confirming that the drug was active at the site of disease. Together, these results support the idea that PALI-2108 delivers its therapeutic effects directly in the colon rather than systemically.

Clinically, the Phase 1b cohort included adults with moderate-to-severe ulcerative colitis who received titrated PALI-2108 for seven days. All patients achieved clinical response based on the modified Mayo Score, and 40 percent reached clinical remission within the same timeframe. Additional improvements were seen in histologic measures of mucosal inflammation, as well as reductions in fecal calprotectin and hsCRP. Importantly, there were no patient discontinuations, consistent with the company’s previous findings in 84 healthy volunteers where no serious adverse events were reported. The combination of clinical improvements, biomarker reductions, and localized target engagement strengthens the rationale for further development.

Dr. Mitch Jones, President and Chief Medical Officer of Palisade Bio, explained that these mechanistic findings provide strong molecular support for the colon-targeted design of PALI-2108. He noted that the suppression of inflammatory and fibrotic signaling pathways directly within colonic tissue, combined with minimal changes in peripheral immune markers, reinforces the goal of improving the therapeutic index of PDE4 inhibition. By concentrating drug activity where inflammation is occurring, the treatment aims to provide efficacy with fewer systemic effects.

The company reported that the Phase 1b results demonstrated consistent reductions in mucosal inflammatory gene expression, fibrosis-related signatures and inflammatory cell markers such as neutrophils and lymphocytes. These changes, which align with increased cAMP levels and decreased PDE4B expression, reflect the expected pharmacology of PDE4 inhibition. Meanwhile, peripheral immune profiles remained largely unchanged, underscoring the localized activity of the therapy. 

Dr. Jones stated that the alignment of clinical outcomes, pharmacokinetic behavior, tissue-level effects and gene expression changes helps further de-risk the program as PALI-2108 progresses toward later-stage clinical development. The overall findings suggest that PALI-2108 may offer a targeted and potentially well-tolerated therapeutic approach for patients with ulcerative colitis