Palisade Bio Presents Positive Preclinical Data Highlighting Potential of PALI-2108 as a Promising Colon-Specific PDE4 Inhibitor for the Treatment of Ulcerative Colitis and Other Inflammatory Bowel Diseases

Two posters presented at Digestive Disease Week (DDW) 2025

Preclinical results indicate that PALI-2108 effectively modulates inflammatory pathways in the colon, promoting a favorable immune response

Company advancing Phase 1a/b study of PALI-2108 and has demonstrated a favorable safety profile in single-ascending-dose cohorts

Carlsbad, CA, May 06, 2025 (GLOBE NEWSWIRE) -- Palisade Bio, Inc. (NASDAQ:PALI) ("Palisade", "Palisade Bio", or the "Company"), a clinical-stage biopharmaceutical company focused on developing and advancing novel therapeutics for patients living with autoimmune, inflammatory, and fibrotic diseases, today announced the presentation of positive preclinical data from PALI-2108, an orally administered, colon-specific phosphodiesterase-4 (PDE4) inhibitor prodrug in development for patients with ulcerative colitis (UC). The presented data highlighted the efficacy and safety profile of PALI-2108 in a mouse model of colitis, with a particular focus on its impact on PDE4B expression, cAMP levels, and TNF-α suppression as well as predicting efficacious PALI-0008 levels in patients.

The first poster titled, "PALI-2108, A Colon-Specific PDE4 Inhibitor Prodrug, as Bioactivated in the Colon and Reduces Colon Tissue PDE4B in a Dose-Dependent Manner, Increasing c-AMP and Suppressing TNF-α in A Mouse Model of Colitis" was presented as a Poster of Distinction as part of the "In Vivo Models of Gastrointestinal Disorders" session at Digestive Disease Week^® (DDW) 2025 being held May 3–6, in San Diego, California.

"We continue to build a growing body of preclinical and clinical results for PALI-2108 that underscores its potential to be an important option for patients with inflammatory bowel diseases, like ulcerative colitis," said Mitch Jones, MD, Ph.D., Chief Medical Officer of Palisade Bio. "We continue to make encouraging progress in our ongoing Phase 1a/b study of PALI-2108 in UC and expect to report topline data from the completed Phase 1a portion of the study by the end of May 2025."

For the preclinical study, colitis was induced in mice using 4% dextran sulfate sodium (DSS) in drinking water. Mice were treated with PALI-2108 at 20, 40, or 80 mg/kg BID, cyclosporine A (40 mg/kg), or apremilast (12.5 mg/kg). Clinical disease progression was monitored through changes in body weight, stool consistency, and fecal blood scores, with the Disease Activity Index (DAI) calculated to quantify disease severity. Colon biopsies were collected for analysis of PDE4B expression, expression of inflammation related genes, cAMP levels, and TNF-α expression.

Pharmacokinetic (PK) modeling using data from healthy volunteers suggested that PALI-2108 has favorable absorption and bioavailability, supporting its potential for clinical use

Key Highlights

• PALI-2108 treatment significantly improved clinical parameters of colitis, including the DAI, body weight, and colon length in a dose-dependent manner.
• PALI-2108 administration resulted in a marked dose-dependent reduction of PDE4B expression in colon tissues, with higher cAMP levels and a notable suppression of TNF-α compared to standard treatments like cyclosporine A and apremilast.
• By increasing cAMP levels and modulating key inflammatory mediators such as TNF-α, PALI-2108 shows significant potential for reducing symptoms associated with UC.
• The preclinical data underscore PALI-2108's efficacy and safety profile, with minimal CNS toxicity and favorable dose-dependent effects.

In addition to the selected Poster of Distinction, Palisade Bio presented a second poster titled, "A Bioinformatic Approach to PALI-2108 Treatment in Ulcerative Colitis Reveals the Potential for Anti-Fibrotic Efficacy with Local PDE4 Inhibition in Intestinal Fibrosis." The presented posters are now available on the Publications page of the Company's website.

The Company is currently conducting a Phase 1a/b single-center, double-blind, placebo-controlled study focused on safety, tolerability, pharmacokinetics, and pharmacodynamics in healthy volunteers, alongside an open-label study involving a patient cohort with UC. For more information about the Phase 1a/b clinical study, visit clinicaltrials.gov and reference identifier NCT06663605.

About Palisade Bio

Palisade Bio is a clinical-stage 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

Any statements contained in this communication that are not statements of historical fact may be deemed to be forward-looking statements for purposes of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include, but are not limited to, statements regarding the safety and tolerability, PK and drug release characteristics of PALI-2108 based on the Company's preclinical studies and preliminary data from the Company's Phase 1b/2a clinical study, indications and anticipated benefits of PALI-2108 and the expected timing of the release of topline data from the Phase 1b/2a clinical study. These forward-looking statements are based on 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 is heavily dependent on the success of PALI-2108, which is in the early stages of clinical development and may not successfully progress through clinical development or receive regulatory approval; preliminary clinical study results or the results from earlier preclinical studies may not be predictive of final or future results and unexpected adverse side effects or inadequate efficacy of PALI-2108 may limit its development, regulatory approval and/or commercialization; the Company needs to raise significant additional funds to support its operations and the continued development of PALI-2108; the timing and outcome of the Company's current and anticipated clinical studies related to its product candidates; indications of use and estimates about the size and growth potential of the markets for the Company's product candidates, and its ability to serve those markets, including any potential revenue generated; the Company's ability to maintain the Nasdaq listing of its securities; the Company's ability to compete effectively in a competitive industry; the Company's ability to identify and qualify manufacturers to provide API and manufacture drug product; the Company's ability to enter into commercial supply agreements; the Company's ability to attract and retain key scientific or management personnel; the accuracy of the Company's estimates regarding expenses, future revenues, capital requirements and needs for additional financing; and the impact of any global event on the Company's business, and operations, and supply. Additional risks and uncertainties can be found in the Company's Annual Report on Form 10-K for the fiscal year ended December 31, 2024, filed with the Securities and Exchange Commission ("SEC") on March 24, 2025, and the Quarterly Reports on Form 10-Q or other SEC filings that are filed thereafter. Investors are cautioned not to put undue reliance on these forward-looking statements. 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.

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