Palisade Bio, Inc. announced the successful completion of its analysis to determine the effects of bioactivated PALI-2108 on TNF-a production in a whole blood (WB) assay. PALI-2108 is Palisade?s orally administered, locally acting, colon-specific phosphodiesterase-4 (PDE4) inhibitor prodrug in development for patients affected by UC. This study included WB samples from 14 clinically healthy adults (five women and nine men).

Twelve samples meeting the inclusion criteria were included for TNF-a measurement and calculation of IC50 values. Donor whole blood was treated with different concentrations of PALI-2108 and two control compounds known to inhibit the PDE4 pro-inflammatory pathway. Blood was then challenged with the pro-inflammatory molecule lipopolysaccharide (LPS).

Anti inflammatory potency was determined by calculating the IC50 values for TNF-a inhibition. Findings from the study demonstrated that PALI-2108 exhibited efficacy in inhibiting TNF-a production induced by LPS in this ex-vivo peripheral whole blood assay. Pre-treatment of human whole blood samples with bioactivated PALI-2108 resulted in a significant reduction in LPS-induced TNF-a production compared to non-pretreated samples.

Specifically, the Company?s proprietary PDE4 inhibitor, shown to be released by the local bioconversion of PALI-2108 prodrug in the colon, demonstrated a mean IC50 for TNF-a inhibition of 0.022 µM, compared to 0.41 µM for apremilast, showcasing its potent anti-inflammatory activity. The study was conducted in collaboration with Paraza Pharma, Inc. based in Montreal, QC.