Palisade Bio (PALI) investor relations material

Drug design and rationale

• PALI-2108 is an oral, once-daily PDE4 prodrug engineered for IBD; it bypasses the upper GI tract and activates in the terminal ileum and colon.

• The approach aims to deliver high local drug concentrations while limiting upper-GI exposure and plasma peaks associated with diarrhea, nausea, vomiting and headache.

• Phase I results showed sustained plasma exposure at IC90 and ~7x higher concentrations in local tissue.

• Historical PDE4 evidence cited included ~20% placebo-adjusted remission with apremilast and 44% with mufemilast; the latter’s higher-dose study showed dose response.

Early clinical evidence

• Phase I SAD, MAD and food-effect studies supported once-daily dosing with food; over 100 patients have been exposed to PALI-2108.

• In a 5-patient UC study over 1 week, modified Mayo results showed 100% response and 40% remission; biomarkers included 70% lower PDE4B and fecal calprotectin.

• In a 5-patient fibrostenotic Crohn’s study over 2 weeks, 20, 25 and 30 mg once daily produced 40% response and 40% remission by SES-CD; two adverse events were reported.

• Dose modeling found systemic IC90 attainment at 15 and 30 mg; at 30 mg, >90% were expected to reach systemic IC90 and tissue exposure was 20x IC90.

• PDE4-associated adverse events typically arose in the first 48–72 hours, with accommodation at later time points, according to management.

Phase II programs and timelines

• The 204-patient UC study compares 15 mg and 30 mg with placebo, with a 12-week induction and treatment through 48-week maintenance; first patient enrolled.

• UC trial assumptions include 12.5% placebo remission, 90% power to detect a 20% difference and 80% power for a 17.5% difference; half of patients will have prior advanced-therapy exposure.

• About 115 sites are planned for UC enrollment; 29 of 30 U.S. sites were activated, with Canadian and Republic of Georgia approvals and further activations planned.

• UC top-line results are targeted by end-2027; enrollment support includes PSI and Iterative Health, with patient education intended to help limit placebo impacts.

• ASCENTRA-CD is a 60-patient, open-label study with centrally read endoscopic response at week 12; site activations were expected before end-2026 and top-line results are guided for Q1 2028.