Core Insights - Palisade Bio announced positive topline results from Phase 1 studies of PALI-2108, a PDE4 B/D inhibitor for fibrostenotic Crohn's disease and ulcerative colitis [1][2] - The study met primary endpoints of safety, tolerability, and pharmacokinetics, supporting progression to Phase 2 development [2][3] Safety & Tolerability - No serious adverse events (SAEs) or treatment-emergent adverse events (TEAEs) related to laboratory values or EKGs were observed across SAD, MAD, and food effect cohorts [7] - In the SAD study (15–450 mg), only mild and reversible TEAEs occurred, limited to the highest dose [7] - The MAD cohorts showed mostly minor TEAEs, with the 15 mg BID dose free of any TEAEs [7] Pharmacokinetics - PALI-2108 achieved therapeutically relevant concentrations in colon tissue up to 24 hours post-dose, confirming its targeted profile [7] - Plasma-to-tissue ratios indicated localized drug activation in the distal gut with low systemic exposure [7] - Population PK modeling supports a therapeutic window aligned with observed safety and tolerability [7] Future Development Plans - Based on the results, Palisade Bio plans to initiate a Phase 1b cohort to further explore safety, tolerability, and pharmacokinetics while completing chronic safety studies [8] - Phase 2 clinical programs will assess PALI-2108's efficacy, safety, and tolerability in patients with fibrostenotic Crohn's disease and moderate to severe ulcerative colitis [8]