Palisade Bio Successfully Completes Microbiome Study Confirming Bacterial Enzymes for Local Bioactivation of Lead Product Candidate, PALI-2108

Rhea-AI Summary

Palisade Bio (Nasdaq: PALI) has successfully completed a microbiome study for its lead product candidate, PALI-2108, aimed at treating Ulcerative Colitis (UC). The study confirmed that beta-glucuronidase, an enzyme important for the bioactivation of PALI-2108, is present at similar levels in mouse, dog, and human microbiota, including healthy humans and those with Crohn's disease and UC.

Key findings include:

• Beta-glucuronidase presence is not significantly different among species or between healthy and diseased human cohorts
• The study supports previous findings of adequate bioactivation of PALI-2108 in Normal Healthy Volunteers and UC patients' stool
• Palisade Bio is advancing towards a Phase 1 clinical study of PALI-2108 for UC treatment, expected to begin before the end of 2024

Positive

• Successful completion of microbiome study confirming bacterial enzymes for PALI-2108 bioactivation
• Beta-glucuronidase presence similar across species and human cohorts, supporting PALI-2108's potential effectiveness
• Advancing towards Phase 1 clinical study for PALI-2108 in UC treatment before year-end 2024

Negative

• None.

Insights

Medical Research Analyst

The successful completion of Palisade Bio's microbiome study for PALI-2108 marks a significant milestone in the development of targeted therapies for ulcerative colitis (UC). The study's findings, demonstrating consistent levels of beta-glucuronidase across species and disease states, are particularly noteworthy.

Key takeaways:

• Beta-glucuronidase levels are similar in dogs, mice and humans, including those with Crohn's disease and UC.
• This enzyme consistency supports the potential for effective bioactivation of PALI-2108 in the intended areas of the GI tract.
• The study utilized advanced metagenomic sequencing and multiple databases for robust enzyme identification.

The implications of these results are substantial. By confirming the presence of necessary bacterial enzymes for local bioactivation, Palisade Bio has effectively de-risked a important aspect of PALI-2108's mechanism of action. This increases the likelihood of successful translation from preclinical to clinical studies.

However, it's important to note that while this study is promising, it doesn't guarantee clinical efficacy. The upcoming Phase 1 trial will be critical in assessing safety and initial efficacy in humans. Investors should monitor this closely, as positive results could significantly boost Palisade Bio's position in the competitive inflammatory bowel disease market.

Biotechnology Analyst

Palisade Bio's microbiome study results for PALI-2108 represent a important step forward in the company's drug development pipeline. The confirmation of bacterial enzyme presence for local bioactivation is a key de-risking event that bolsters the potential of their lead candidate.

From a biotech perspective, several aspects stand out:

• The company's approach leverages the gut microbiome, aligning with cutting-edge trends in drug development.
• The prodrug strategy, utilizing beta-glucuronidase for activation, potentially allows for targeted drug delivery and reduced systemic side effects.
• The consistency of enzyme levels across species supports the translatability of preclinical data to humans, a critical factor in drug development success.

Moreover, Palisade's pipeline diversity, with PALI-1908 targeting fibrostenotic Crohn's Disease, demonstrates a strategic approach to maximizing their technology platform. This could provide multiple shots on goal and mitigate risk for investors.

However, it's important to remember that many promising candidates fail in later-stage trials. The upcoming Phase 1 study for PALI-2108, slated to begin by the end of 2024, will be a critical inflection point. Positive results could significantly enhance Palisade's valuation and attract potential partnerships or acquisition interest from larger pharmaceutical companies.

Findings demonstrate that the microbiome and enzymes are sufficient in mouse, dog, and Normal Healthy Volunteers (NHV) and Ulcerative Colitis (UC) patients

Company advancing toward commencement of Phase 1 human clinical study of PALI-2108 for the treatment of UC before year end

Carlsbad, CA, July 29, 2024 (GLOBE NEWSWIRE) -- Palisade Bio, Inc. (Nasdaq: PALI) (the “Company”), a biopharmaceutical company focused on developing and advancing novel therapeutics for patients living with autoimmune, inflammatory, and fibrotic diseases, today 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,” commented 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.

About Palisade Bio

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, please go to www.palisadebio.com.

Forward Looking Statements

This communication contains “forward-looking” statements for purposes of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include statements regarding the Company’s intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things: the extent of our cash runway; our ability to successfully develop our licensed technologies; estimates about the size and growth potential of the markets for our product candidates, and our ability to serve those markets, including any potential revenue generated; future regulatory, judicial, and legislative changes or developments in the United States (U.S.) and foreign countries and the impact of these changes; our ability to maintain the Nasdaq listing of our securities; our ability to build a commercial infrastructure in the U.S. and other markets; our ability to compete effectively in a competitive industry; our ability to identify and qualify manufacturers to provide API and manufacture drug product; our ability to enter into commercial supply agreements; the success of competing technologies that are or may become available; our ability to attract and retain key scientific or management personnel; the accuracy of our estimates regarding expenses, future revenues, capital requirements and needs for additional financing; our ability to obtain funding for our operations; our ability to attract collaborators and strategic partnerships; and the impact of the COVID-19 pandemic or any global event on our business, and operations, and supply. Any statements contained in this communication that are not statements of historical fact may be deemed to be forward-looking statements. These forward-looking statements are based upon the Company’s current expectations. Forward-looking statements involve risks and uncertainties. The Company’s actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, which include, without limitation, the Company’s ability to advance its nonclinical and clinical programs, the uncertain and time-consuming regulatory approval process; and the Company’s ability to secure additional financing to fund future operations and development of its product candidates. Additional risks and uncertainties can be found in the Company’s Annual Report on Form 10-K for the fiscal year ended December 31, 2023 and Quarterly Report on Form 10-Q, filed with the Securities and Exchange Commission (“SEC”) on March 26, 2024 and May 13, 2024, respectively. These forward-looking statements speak only as of the date hereof and the Company expressly disclaims any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in the Company’s expectations with regard thereto or any change in events, conditions or circumstances on which any such statements are based.

Investor Relations Contact
JTC Team, LLC
Jenene Thomas
833-475-8247
PALI@jtcir.com

Source: Palisade Bio

FAQ

What is the significance of the microbiome study for Palisade Bio's PALI-2108?

The microbiome study confirms that beta-glucuronidase, important for PALI-2108's bioactivation, is present at similar levels in mouse, dog, and human microbiota, including healthy humans and those with UC. This supports the potential effectiveness of PALI-2108 in treating Ulcerative Colitis.

When is Palisade Bio (PALI) expected to begin the Phase 1 clinical study for PALI-2108?

Palisade Bio (PALI) is expected to begin the Phase 1 clinical study for PALI-2108 in the treatment of moderate-to-severe Ulcerative Colitis before the end of 2024.

What is PALI-2108 being developed to treat?

PALI-2108 is being developed by Palisade Bio (PALI) for the treatment of moderate-to-severe Ulcerative Colitis (UC).

What did the microbiome study reveal about beta-glucuronidase levels in different species?

The study revealed that beta-glucuronidase levels are not significantly different among dog, mouse, and human microbiota, as well as between healthy humans and those with Crohn's disease and Ulcerative Colitis.