Palisade Bio Announces Positive Data from Two Ex Vivo Translational Studies of PALI-2108 for the Treatment of Ulcerative Colitis

Targeted, better-tolerated oral PDE4 inhibitors are an unmet need in inflammatory bowel disease (IBD)

PALI-2108 demonstrates in ex vivo studies; targeted activation and reduced side effects, potentially enhancing patient compliance compared to existing PDE4 inhibitors

Data presented at the American College of Gastroenterology’s (ACG) 2024 Annual Scientific Meeting

Carlsbad, CA, Oct. 31, 2024 (GLOBE NEWSWIRE) — Palisade Bio, Inc. (Nasdaq: PALI) (“Palisade,” “Palisade Bio” or the “Company”), a biopharmaceutical company dedicated to developing novel therapeutics for patients with autoimmune, inflammatory, and fibrotic diseases has announced the presentation of data from two translational studies demonstrating the ex vivo bioactivation of PALI-2108 in stool samples and whole blood. This orally administered, colon-specific phosphodiesterase-4 (PDE4) inhibitor prodrug is in development for patients with ulcerative colitis (UC).

The poster titled “Colonic Bioactivation and Potent TNFα Inhibition of PALI-2108 in Human Clinical Studies: A Promising PDE4 Inhibitor Prodrug for the Oral Treatment of Ulcerative Colitis,” was presented by Dr. Mitch Jones, Chief Medical Officer of Palisade Bio, at the ACG 2024 Annual Scientific Meeting, held October 25-30, 2024, in Philadelphia, PA.

“The design of PALI-2108 ensures that activation is targeted primarily in the colon, which should minimize systemic exposure and potential central nervous system side effects. By demonstrating reduced systemic exposure, we believe PALI-2108 can effectively address the toxicity issues commonly associated with other PDE4 inhibitors like roflumilast and apremilast,” stated Dr. Mitch Jones, CMO of Palisade. “These ex vivo data reinforce the potential of PALI-2108 as an innovative therapeutic option for managing UC. We remain committed to advancing toward the launch of our Phase 1 study and are excited to further explore the potential of this novel, orally delivered, intestinally activated PDE4 inhibitor prodrug.”

Researchers assessed prodrug conversion in stool samples from six healthy individuals and six patients with UC using liquid chromatography-mass spectrometry (LC-MS). The enzymatic activity was evaluated by measuring the half-lives of samples from each donor. PALI-2108 was spiked into stool homogenates at a concentration of 100 μM, followed by a 24-hour incubation period.

Additionally, the impact of the active phosphodiesterase 4 (PDE4) inhibitor, PALI-0008, on lipopolysaccharide (LPS)-induced tumor necrosis factor-alpha (TNFα) production was investigated through an ex vivo assay using peripheral whole blood. Whole blood from twelve healthy human donors was pre-treated with PALI-0008 before being challenged with LPS at 1 µg/ml for 24 hours. TNFα production was quantified, and the IC50 values for apremilast and PALI-2108 were calculated.

Furthermore, a microbiome study was conducted in collaboration with CosmosID to evaluate the abundance of the beta-glucuronidase enzyme in microbiome samples from mice, dogs, healthy humans, and UC patients. Publicly available data for dog, mouse, and human whole genome metagenomic sequencing were obtained from the NCBI Sequence Read Archive. These samples were uploaded to the CosmosID-HUB (app.cosmosid.com) for functional identification of genes, enzymes, and pathways, utilizing MetaCyc, Gene Ontology, and Enzyme Commission databases.

Key Highlights

• PALI-2108 was successfully bioactivated into its active form, PALI-0008, in stool samples from both normal healthy volunteers (NHV) and UC patients, achieving a high conversion rate of 90.1% at 24 hours.
• PALI-0008 demonstrated significant inhibition of TNFα production in human whole blood, with an IC50 of 0.022 μM, indicating strong potency.
• PALI-0008 exhibited approximately a 20-fold higher potency in reducing TNFα production compared to apremilast, underscoring its potential efficacy.
• The microbiome study revealed consistent levels of β-glucuronidase across different species and conditions, supporting the activation mechanism of PALI-2108.
• The consistent abundance of this enzyme suggests that PALI-2108 could be effective across diverse patient populations, including those with UC.

The Company is advancing PALI-2108 toward a Phase 1 single-center, double-blind, placebo-controlled study focused on safety, tolerability, pharmacokinetics, and pharmacodynamics in healthy volunteers, alongside an open-label study involving UC patients. Preparations for the clinical study are ongoing, and the Company is on track to initiate patient dosing before year-end. For more information about the Company’s next-generation precision therapies for immune, inflammatory, and fibrotic diseases, please visit palisadebio.com.

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; the timing and outcome of our current and anticipated applications and studies related to our product candidates; 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 most recent Quarterly Report on Form 10-Q for the period ended June 30, 2024, filed with the Securities and Exchange Commission on March 26, 2024 and August 12, 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
908-824-0775
PALI@jtcir.com