PALI‑2108 Phase 1b Translational Readout at ECCO 2026

A press release describes Phase 1b translational findings for PALI‑2108 presented at ECCO 2026, pairing early symptom-score signals with colon tissue readouts that included histology and RNA sequencing over a short treatment interval.

The report describes adults with moderate-to-severe ulcerative colitis who received seven days of dosing, with outcomes framed around rapid clinical change alongside biopsy-based translational measures. The emphasis is on aligning short-duration clinical observations with local tissue pharmacology rather than on longer follow-up.

The therapy is described as a once-daily, colon-targeted oral PDE4 prodrug designed to remain pharmacologically inactive until it undergoes local bacterial bioactivation in the terminal ileum and colon. According to the company, the activation strategy is intended to concentrate PDE4 inhibition at sites of intestinal inflammation and fibrosis and to limit systemic exposure, with the stated goal of reducing tolerability limitations seen with prior systemic PDE4 inhibitors. The same background description states that preventing absorption in the upper gut and reducing peak plasma levels are engineered features of the approach, with the goal of improving the overall therapeutic index. In that framing, colon biopsy sampling is described as a direct way to examine whether the intended site-restricted activity is reflected in tissue measurements.

In the Phase 1b ulcerative colitis cohort described in the release, five adults received titrated PALI‑2108 for seven days, and the sponsor reported a 100% clinical response rate (5/5) and a 40% clinical remission rate (2/5) as assessed by modified Mayo Score. Alongside these clinical-score outcomes, the release also describes histologic improvement in colon tissue and reductions in fecal calprotectin and high-sensitivity C-reactive protein (hsCRP) over the same brief period. The company characterized the combined symptom-score, histology, and biomarker package as a rapid, early signal set observed within a one-week dosing window. These are presented as short-duration observations summarized by the sponsor rather than as longer-term efficacy results.

Translational findings from colon biopsy RNA sequencing are presented as a central element of the ECCO poster, with the sponsor reporting significant downregulation of inflammatory and fibrosis-associated gene expression programs. Pathway-level analyses using PROGENy-derived scoring were described as showing suppression of TNF-α, JAK–STAT, NF-κB, MAPK, and TGF-β pathway activity, with additional mention of reduced inflammatory cell signatures based on cellular deconvolution analyses. The release also reports localized pharmacology in colon biopsies, including reduced mucosal PDE4B expression accompanied by increased tissue cAMP levels, and notes that peripheral blood immune profiles remained largely unchanged; the company framed this contrast as consistent with localized colonic activity. In the sponsor’s narrative, transcriptomic pathway scoring and tissue pharmacodynamics together form the mechanistic throughline for the reported readout.

For safety, the release states that there were no ulcerative colitis patient discontinuations in the seven-day cohort and references earlier findings of no serious adverse events across 84 healthy volunteers, describing an “encouraging safety profile across 89 subjects.”

Looking ahead, the company states it is advancing PALI‑2108 into a Phase 2 ulcerative colitis study designed to evaluate clinical remission, clinical response, and pharmacodynamic biomarkers over 12 weeks, with an extension phase intended to assess maintenance of remission. In the release, the Phase 2 program is described in broad terms as a 12-week ulcerative colitis study evaluating clinical remission, clinical response, and pharmacodynamic biomarkers, followed by an extension phase assessing maintenance of remission.

Key Takeaways:

• The sponsor reported modified Mayo Score–based clinical response in all five treated patients and clinical remission in a subset after seven days of titrated dosing.
• Colon biopsy readouts were described as showing RNA-seq–based suppression of inflammatory and fibrosis-associated programs alongside PDE4B/cAMP tissue pharmacodynamic signals, with largely unchanged peripheral blood immune profiles.
• Phase 2 plans were described as a 12-week ulcerative colitis study evaluating remission, response, and pharmacodynamic biomarkers, with an extension phase assessing maintenance of remission.