Palisade Bio Announces PALI-2108 Clinical Data
Palisade Bio announced topline data from its Phase 1b clinical study evaluating PALI-2108, a once-daily oral PDE4 inhibitor prodrug designed to be selectively bioactivated in the ileum and colon, in patients with fibrostenotic Crohn's disease. This Phase 1b study demonstrated favorable safety and tolerability, robust pharmacodynamic target engagement in ileal tissue, and encouraging early signals of clinical activity in the five participating patients. These data support the continued development of PALI-2108 as a potential first therapy designed to address both inflammatory and fibrotic components of Crohn's disease. No serious adverse events reported. No clinically significant laboratory, vital sign, or EKG abnormalities observed. PALI-2108 was generally well tolerated across all patients. All adverse events were mild and self-limited; no PDE4 class-related adverse events observed. Pharmacokinetic profile supported once-daily dosing with measurable systemic and tissue exposure; patients achieved plasma drug concentrations above IC90 by the end of titration with doses as low as 20 mg daily. Tissue levels were above IC90, and increased over plasma by approximately 3x in ileum and 5x in colon by Day 14. Robust ileal pharmacodynamic activity demonstrated by a mean 41% increase in tissue cAMP, a key marker of PDE4 inhibition, with no decreases observed across patients. Ileal target engagement exceeded prior colonic cAMP responses observed in ulcerative colitis studies, supporting effective localized drug activation in the ileum. Mean fecal calprotectin decreased by approximately 59% after 14 days of treatment. Strong inverse correlation between ileal cAMP and FCP, linking target engagement with reduction in inflammatory burden. Plasma and tissue biomarker trends were consistent with modulation of inflammatory and fibrosis-related pathways. Mean SES-CD improved by -3.8 points. Overall, 40% of patients achieved endoscopic response and 40% achieved endoscopic remission. Convergent improvements observed across pharmacodynamic, biomarker, and endoscopic endpoints. In the context of published benchmarks, Week 12 endoscopic response rates of 29%-40% and remission rates of 19%-24% have been reported for risankizumab, and 34%-46% and 19%-30% for upadacitinib. While differences in trial design and timing preclude direct comparison, the early endoscopic improvements observed with PALI-2108 at Week 2 fall within these ranges.
