Palisade Bio presents preclinical data on PALI-2108 at DDW 2024

Palisade Bio announced the presentation of positive preclinical data from PALI-2108, an orally administered, locally acting colon-specific Phosphodiesterase-4 inhibitor prodrug in development for patients affected by UC, at DDW 2024 being held in Washington, D.C., May 18-21, 2024. The poster titled, “Local Bioactivation and efficacy of PALI-2108: A Promising PDE4 Inhibitor Prodrug for Ulcerative Colitis Treatment,” is being presented by Dr. Mitch Jones as part of the Animal Models of IBD: Pre-Clinical Treatment of Intestinal Inflammation session being held today, May 21, 2024. The preclinical data highlighted in the poster reveal significant advancements in assessing on-target PDE4 binding within colon tissue homogenates when dosed with apremilast, PALI-2108, or Vehicle, utilizing a classic cellular thermal shift assay to detect changes in thermal stability. To comprehensively evaluate PALI-2108’s efficacy across various doses, researchers employed an acute colitis model in mice induced by 4% DSS in drinking water from Day 1 to Day 8. Mice received twice-daily treatments of PALI-2108 at 20, 40, and 80 mg/kg/dose BID, while cyclosporin A and apremilast were administered at 40 and 12.5 mg/kg/dose BID, respectively. The assessment of DSS-induced colitis included monitoring Body Weight score, Stool Consistency score, and Fecal Blood score from Day 1 to Day 8, with evaluations conducted 1 to 2 hours post-dosing. Overall disease state was measured using a Disease Activity Index score, calculated by pooling the three in-life scores, assessed daily from Days 1 to 8. Furthermore, a single oral dose of the prodrug PALI-2108 at 43 mg/kg and active PALI-0008 at 0.1, 0.3, 1, and 3 mg/kg was administered to dogs, with a focus on monitoring key clinical adverse events, including emesis. Remarkably, the PALI-2108 prodrug prevented emesis observed with lower doses of the PDE4 active moiety in the model, demonstrating an enhanced therapeutic window. Key Findings: PALI-2108 demonstrates similar target engagement to the PDE4 inhibitor, apremilast, which is approved for use in psoriasis and psoriatic arthritis. In a DSS colitis mouse model, PALI-2108 significantly prevented colon length reduction in dose dependent manner, and showed dose dependent improvements in body weight score, stool consistency score, fecal blood score, overall disease activity index score, and AUC of DAI over the course of the study. Importantly, PALI-2108 exhibited a dose-dependent efficacy response in two DSS colitis mouse models, achieving efficacy comparable to doses of apremilast considered intolerable for human use in UC patients. No systemic toxicity in dogs and large therapeutic window due to local activation.