Palisade Bio's PALI-2108 Shows Promise in Preclinical Ulcerative Colitis Trials

Palisade Bio, Inc. (Nasdaq: PALI) has presented positive preclinical data for its lead asset, PALI-2108, an orally administered, colon-specific phosphodiesterase-4B (PDE4B) inhibitor prodrug in development for patients affected by moderate-to-severely active ulcerative colitis (UC). The data, presented at the Crohn’s & Colitis Congress in San Francisco, CA, on February 10, 2025, demonstrated the drug's potential in reducing colitis symptoms in a mouse model without causing central nervous system (CNS) toxicity associated with systemic exposure.

PALI-2108 is designed to act locally at the site of disease, targeting the colon-specific PDE4B enzyme. The drug's unique design incorporates a galactose-derived sugar moiety that ensures minimal absorption until cleaved by the colonic bacterium enzyme β-glucuronidase, leading to localized bioactivation and colon-specific distribution with limited systemic exposure. This targeted approach allows PALI-2108 to achieve high local concentrations in the colon while minimizing systemic side effects.

In preclinical studies, PALI-2108 demonstrated clear dose-dependent improvements in clinical outcome measures and outperformed standard treatments in a dextran sulfate sodium (DSS) colitis mouse model. The drug also showed superior potency and target engagement compared to other PDE4 inhibitors, such as apremilast, and exhibited a larger therapeutic window due to its local activation. Additionally, PALI-2108 demonstrated dose-dependent efficacy in two DSS colitis mouse models, achieving comparable efficacy to doses of apremilast considered intolerable for human use.



PALI-2108's colon-specific bioactivation and delayed-release, extended-release characteristics have the potential to improve patient adherence and treatment outcomes. The drug's delayed-release and extended-release characteristics provide sustained, dose-dependent drug exposure with high local concentrations in the colon, which could enhance efficacy and simplify the treatment regimen for patients with UC.

Palisade Bio's precision medicine approach, targeting patients with elevated PDE4B expression, has the potential to significantly impact the market size and commercial success of PALI-2108. By identifying patients who overexpress PDE4B, the Company can maximize the efficacy of its UC PDE4 prodrug therapeutic and enhance therapeutic outcomes. This targeted approach is supported by the Company's bioinformatics and machine learning research, which has identified a measurable threshold of elevated PDE4B expression across more than 1,600 patients and 10 studies, enabling the identification of over-expressing patients in over 70% of cases.



In summary, Palisade Bio's PALI-2108 has shown promise in preclinical trials for the treatment of ulcerative colitis. The drug's colon-specific bioactivation, delayed-release, and extended-release characteristics, along with the Company's precision medicine approach, position PALI-2108 as a potential novel therapy for patients with UC. As the Company advances towards Phase 1 clinical studies, investors and the biopharma industry will closely monitor the progress of this innovative drug candidate.

Dr. Mitch Jones, Chief Medical Officer of Palisade Bio, commented on the positive preclinical data, "PALI-2108 continues to demonstrate promise as a novel therapy for UC, with colon-selective bioactivation, an expanded therapeutic window, reduced CNS toxicity, potent PDE4 inhibitory activity, and impressive efficacy in preclinical models. We are pleased with our growing body of evidence, including support for a precision medicine approach and the selection of potential responders, which validate the continued development of this program. We are working diligently to launch our Phase 1 study later this year, and we are eager to continue to gain experience on the potential of this groundbreaking PDE4 inhibitor prodrug therapy. The journey ahead holds great promise for advancing UC treatment, and we are committed to making a meaningful impact for patients."