
Core Insights - PALI-2108 is a promising orally delivered, colon-specific PDE4 inhibitor prodrug for Ulcerative Colitis (UC) treatment, demonstrating safety, efficacy, and tolerability in preclinical studies [1][3][8] - The company plans to initiate Phase 1 human clinical trials for PALI-2108 by the end of 2024 [1] Group 1: Preclinical Data and Efficacy - Preclinical studies showed PALI-2108 exhibited a dose-dependent efficacy response in two DSS colitis mouse models, achieving efficacy comparable to intolerable doses of apremilast for human use [1][8] - Significant advancements were made in assessing on-target PDE4 binding within colon tissue, utilizing a cellular thermal shift assay (CETSA) [3] - In a DSS colitis mouse model, PALI-2108 significantly prevented colon length reduction and improved various disease activity scores in a dose-dependent manner [8] Group 2: Safety and Therapeutic Window - PALI-2108 demonstrated no systemic toxicity in dogs, indicating a large therapeutic window due to its local activation [8] - A single oral dose of PALI-2108 prevented emesis observed with lower doses of the active PDE4 moiety, showcasing an enhanced therapeutic profile [5][8] Group 3: Company Overview - Palisade Bio is focused on developing novel therapeutics for autoimmune, inflammatory, and fibrotic diseases, aiming to transform treatment landscapes with targeted approaches [9]