Palisade Bio Successfully Completes Microbiome Study Confirming Bacterial Enzymes for Local Bioactivation of Lead Product Candidate

Palisade Bio, Inc. recently announced the successful completion of a microbiome study demonstrating that beta-glucuronidase is present at similar levels among dog, mouse, and human microbiota as well as within healthy humans and those with Crohn’s disease (CD) and ulcerative colitis (UC).

“We are pleased to bolster our growing body of data for PALI-2108. The study completed by CosmosID, which uses direct identification of beta-glucuronidase by multiple databases, indicates that the presence of this enzyme is not significantly different among the species or between healthy and disease human cohorts. This allows the prodrug to break down in the areas of the GI tract where we are trying to deliver the active drug and confirms our previous findings of adequate bioactivation of PALI-2108 in NHV and UC patients’ stool,” said Dr. Mitch Jones, CMO of Palisade Bio.

Publicly available data for dog, mouse, and human whole genome metagenomic sequencing was obtained from the NCBI Sequence Read Archive (https://www.ncbi.nlm.nih.gov/sra). These samples were found by searching for metagenomic data for the specific host species and further filtered for Illumina paired-end whole genome sequencing (WGS) data.

These data samples were subsampled to 6 million reads each to allow for accurate functional pathway and gene identification while keeping the maximum number of samples for comparison. After subsampling, the samples were uploaded to the CosmosID-HUB (app.cosmosid.com) for functional identification of genes, enzymes, and pathways utilizing the MetaCyc, Gene Ontology, and Enzyme Commission databases.

Findings from the study demonstrated that although there are overall significant differences by species among the functional data as a whole, beta-glucuronidase-specific functions are not significant. The superpathway of beta D-glucuronoside degradation does show significant differences by species, but this pathway does not directly identify the enzyme beta-glucuronidase. Beta-D-glucuronoside is the substrate for beta-glucuronidase (MetaCyc pathway), which may imply that the enzyme is present. However, direct identification of beta-glucuronidase by both EC and GO databases indicate that the presence of this enzyme is not significantly different among the species or between healthy and disease human cohorts.

Palisade continues to advance PALI-2108 for the treatment of moderate-to-severe UC toward a Phase 1 clinical study, expected to be initiated before the end of 2024. The Company’s PALI-1908 candidate is a microbiota-activated PDE4 inhibitor prodrug that leverages the advancements made with PALI-2108 and is being developed for the treatment of fibro stenotic Crohn’s Disease.

Palisade Bio is a biopharmaceutical company focused on developing and advancing novel therapeutics for patients living with autoimmune, inflammatory, and fibrotic diseases. The company believes that by using a targeted approach with its novel therapeutics it will transform the treatment landscape. For more information, visit www.palisadebio.com.