Palisade Bio to Present Preclinical Results for PALI-2108 Showing Key Fibrotic Pathway Engagement in Crohn's and UC

On November 21, 2024, Palisade Bio, a clinical-stage biopharmaceutical company dedicated to developing innovative treatments for autoimmune, inflammatory, and fibrotic diseases, released preclinical data for their new drug candidate, PALI-2108. This prodrug, a local PDE4 inhibitor, demonstrated significant potential in treating fibrostenotic Crohn’s disease in preclinical tests. The recent studies utilized the Dextran Sulfate Sodium (DSS) colitis mouse model, where PALI-2108 showed a dose-dependent impact on crucial fibrotic pathways, highlighting its promise as an effective treatment option.

The findings will be shared in a presentation titled "Detailing Characteristics of Fibrostenotic Crohn’s Disease Biology & the Potential of a Local PDE4 Inhibitor Prodrug to Minimize Off-Target Effects & Maximize Efficacy" by Dr. Mitch Jones, the Chief Medical Officer of Palisade Bio, at the 8th Annual Antifibrotic Drug Development Summit in Boston, MA, from November 19-21, 2024.

Dr. Jones emphasized the significant unmet need in Crohn’s disease treatment, noting that many patients suffer from severe fibrosis leading to stenosis, often requiring surgical procedures. He highlighted that the DSS mouse model data for PALI-2108 suggests it could be a potent targeted anti-inflammatory and anti-fibrotic therapy for fibrostenotic Crohn’s disease. The drug appears to engage and modify critical fibrotic pathways directly in the intestinal and colonic mucosa, addressing the primary cause of fibrosis while reducing systemic side effects typically associated with systemic PDE4 inhibitors. This could provide a safer, more effective treatment alternative for patients.

The preclinical study assessed PALI-2108 in an inflammatory bowel disease (IBD) animal model complicated by intestinal fibrosis. The prodrug, which activates locally in the ileum and colon, influenced key fibrotic pathways linked to Crohn’s disease and ulcerative colitis (UC). Detailed gene expression analysis indicated that PALI-2108 modulated 187 genes involved in the major fibrotic pathways of IBD, showing both upregulation and downregulation of critical markers. This suggests the potential of PALI-2108 to prevent or reverse fibrotic progression in the intestines.

The research also demonstrated that PALI-2108 reduced key intracellular markers of inflammation and fibrosis in the colon, such as PDE4B expression, while increasing cAMP levels, essential for maintaining tissue balance. The dose-response data showed that higher doses of PALI-2108 enhanced the fibrotic signature, reinforcing its potential as a localized treatment for fibrostenotic Crohn’s disease. The findings suggest that PALI-2108 could offer improved safety and therapeutic benefits compared to existing treatments. Unlike systemic PDE4 inhibitors, PALI-2108 is designed for local activation, potentially minimizing common side effects like nausea, which are often associated with oral PDE4 inhibitors used in other conditions like fibrotic COPD and inflammatory diseases.

Palisade Bio is currently evaluating PALI-2108 in a Phase 1 single-center, double-blind, placebo-controlled study focusing on its safety, tolerability, pharmacokinetics, and pharmacodynamics in healthy volunteers, along with an open-label study involving UC patients. Preliminary data from the Phase 1 study is expected in the first half of 2025.

Palisade Bio aims to transform the treatment landscape for autoimmune, inflammatory, and fibrotic diseases through targeted approaches with novel therapeutics. The Company believes that the comprehensive data gathered from the ongoing studies will support their precision medicine strategy, which seeks to identify patient responders for future clinical trials.