Palisade Bio’s PALI-2108 Sees 47.5% SES-CD Reduction, Advances to Phase 2
PALI-2108 showed favorable safety with no serious adverse events and robust pharmacodynamic engagement in five fibrostenotic Crohn’s patients, achieving a 47.5% mean SES-CD reduction after two weeks. 40% of patients achieved endoscopic response and remission, while plasma and ileal PK data support once-daily oral dosing, justifying progression to a Phase 2 trial in moderate-to-severe disease.
1. Phase 1b Trial Design and Results
The Phase 1b study enrolled five patients with confirmed fibrostenotic Crohn’s disease receiving once-daily oral PALI-2108 over 14 days. No serious adverse events occurred; all adverse events were mild and self-limited. Endoscopic assessments showed a 47.5% mean SES-CD score reduction, with 40% of patients achieving both endoscopic response and remission by Day 14.
2. Pharmacokinetics and Pharmacodynamics
Plasma concentrations exceeded the IC90 threshold at doses as low as 20 mg daily, while ileal and colonic tissue levels were approximately threefold and fivefold higher than plasma by Day 14. A mean 41% increase in tissue cAMP confirmed robust PDE4 inhibition, with a 59% mean fecal calprotectin reduction and strong inverse correlation (r = −0.92) between cAMP and inflammatory biomarkers.
3. Plans for Phase 2 Expansion
Based on these topline data, the company will initiate a Phase 2 trial in moderate-to-severe Crohn’s disease, including luminal and fibrostenotic patients to assess clinical remission, response and anti-fibrotic effects over 12 weeks. Regulatory clarity for broader luminal Crohn’s indications could more than double the addressable patient population without anatomical constraints.