Palisade Bio (PALI) investor relations material

Program overview and clinical progress

• Lead candidate PALI-2108 is a once-daily oral PDE4 inhibitor prodrug targeting inflammatory and fibrotic diseases, with phase I completed and phase II programs initiated for ulcerative colitis and Crohn's disease.

• Phase I data showed favorable safety, sustained plasma exposure above IC90, targeted ileal and colonic distribution, and early clinical and endoscopic signals.

• IND and CTA clearances have been obtained for phase II studies in the US and Canada, with enrollment underway for 204 UC patients and 60 Crohn's patients across North America and Europe.

• PALI-2108's targeted bioactivation in the distal ileum and colon aims to overcome the therapeutic window limitations of previous PDE4 inhibitors.

Mechanism of action and differentiation

• PDE4 inhibition is a validated anti-inflammatory and anti-fibrotic mechanism, but prior drugs were limited by tolerability and dosing constraints.

• PALI-2108 is designed for local activation in disease tissue, reducing systemic side effects and enabling a wider therapeutic window.

• The prodrug approach avoids upper GI exposure, mitigating common PDE4-related side effects like nausea and diarrhea.

Phase I results and rationale for phase II

• In phase I, all five UC patients achieved clinical response after seven days, with two reaching endoscopic response and remission; similar positive signals were seen in fibrostenotic Crohn's patients.

• Clinical signals were supported by direct evidence of drug exposure and target engagement in intestinal tissues.

• Consistency across clinical, histologic, and pharmacodynamic measures in small cohorts provided confidence to expand into broader Crohn's populations.