Palisade Bio (PALI) Study result summary

Study design and objectives

• Phase 1b open-label, single-arm study evaluated PALI-2108 in five patients with fibrostenotic Crohn's disease, all with symptomatic ileal strictures and mean disease duration over 15 years.

• Patients received once-daily oral dosing (20, 25, or 30mg) for 14 days, with safety, pharmacokinetics, pharmacodynamics, and endoscopic efficacy as key endpoints.

• All patients completed the study; 80% were on concomitant biologics.

• Study included paired ileal biopsies and advanced molecular analyses.

Safety and tolerability

• No serious adverse events, study discontinuations, or PDE4 class-related adverse events were reported; all adverse events were mild and resolved without intervention.

• Two patients experienced mild, possibly related treatment-emergent adverse events (fatigue, abdominal discomfort).

• No nausea, vomiting, diarrhea, or clinically significant laboratory, vital sign, or EKG abnormalities occurred.

• Safety profile was consistent with prior ulcerative colitis studies.

Pharmacokinetics and pharmacodynamics

• Once-daily dosing achieved plasma and ileal tissue drug concentrations above IC90 in all patients.

• Ileum tissue drug levels were 3x higher than plasma at steady state, and colon levels were ~5x higher by Day 14.

• Mean 41% increase in tissue cAMP, with robust ileal target engagement exceeding prior colonic responses.