Palisade Bio (PALI) Study result summary

Study design and objectives

• Phase 1b open-label, 2-week study evaluated PALI-2108 in five patients with fibrostenotic Crohn's disease, all with symptomatic ileal strictures, advanced disease, and long disease duration; most were on background biologic therapy.

• Patients received once-daily oral dosing (20, 25, or 30 mg) for 14 days, including a 10-day titration period.

• Intensive PK/PD biomarker assessments, paired ileal biopsies, and endoscopic scoring (SES-CD) were performed.

• Primary endpoint was safety; secondary endpoints included PK, PD, and clinical activity.

• All patients completed the study; 80% were on concomitant biologics, and mean disease duration was over 15 years.

Safety and tolerability

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

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

• Mild fatigue and abdominal discomfort were the only possibly related adverse events.

• Safety profile was consistent with prior ulcerative colitis studies.

• PALI-2108 was generally well tolerated across all patients.

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, confirming targeted delivery.

• Mean 41% increase in tissue cAMP, a key marker of PDE4 inhibition, with robust ileal target engagement exceeding prior colonic responses.

• Strong inverse correlation (r = 0.92) between ileal cAMP and fecal calprotectin, linking mechanism to clinical outcomes.