Cure8 news brief
Early Phase 1 findings suggest a gut-targeted PDE4 prodrug may engage its target in diseased tissue and produce early improvements in symptoms, endoscopy, and tissue inflammation — findings that, if confirmed in Phase 2, could offer a new oral option for some people with UC or fibrostenotic Crohn’s disease.
The work also explores biomarkers and the microbiome to help identify who might benefit.
Adult patients with ulcerative colitis or Crohn’s disease (including those with fibrostenotic disease), clinicians following emerging IBD therapies, researchers in IBD drug development, and patients on concomitant biologic therapy interested in oral adjunctive options.
Palisade Bio presented Phase 1a/1b clinical and translational data for PALI-2108, an investigational oral, locally activated PDE4 inhibitor prodrug, at ACG 2026.
Small open-label cohorts in moderate-to-severe UC and fibrostenotic Crohn’s disease showed early clinical, endoscopic, pharmacokinetic, and tissue biomarker signals (including increased tissue cAMP, reduced PDE4B expression, reductions in fecal calprotectin, and histologic changes).
The company reported pharmacokinetic support for once-daily dosing and microbiome/transcriptomic analyses suggesting possible precision-medicine approaches. These were short, placebo‑free Phase 1 cohorts and the company says larger randomized Phase 2 studies are ongoing.
These reports come from small, short-duration, open-label Phase 1 cohorts without placebo control; the findings are hypothesis‑generating and need confirmation in larger randomized Phase 2 trials. The source is a company press release summarizing poster abstracts presented at ACG 2026.
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Early clinical data suggest PALI-2108 may affect both inflammation and fibrosis in Crohn’s disease and shows biomarker changes (like fecal calprotectin) that could matter to people monitoring disease activity.
If fecal GP2 reliably reflects UC activity and microbial changes, it could become a noninvasive marker to track inflammation or to study disease mechanisms that differ between UC and CD.
Non-invasive fecal lipid markers could help differentiate UC from CD and improve diagnostic molecular profiling in IBD if validated, which may be useful for patients and clinicians seeking less-invasive diagnostic tools.
