Palisade Bio Announces First Patients Dosed in Phase 1b Study of Oral First-In-Class PDE4 Inhibitor Prodrug, PALI-2108, for the Treatment of Fibrostenotic Crohn's Disease (FSCD)

First dual-acting anti-inflammatory and anti-fibrotic candidate in development for FSCD, a condition with no approved therapies

Topline safety, PK, and PD data anticipated in Q1 2026

Advances ongoing development of PALI-2108 across fibrostenotic Crohn's disease and ulcerative colitis, with Phase 2 IND submission planned for H1 2026

Carlsbad, CA, Oct. 20, 2025 (GLOBE NEWSWIRE) -- Palisade Bio, Inc. (NASDAQ:PALI) ("Palisade" or the "Company"), a clinical-stage biopharmaceutical company developing precision therapies for autoimmune, inflammatory, and fibrotic diseases, today announced that the first patients have been dosed in its Phase 1b clinical study evaluating PALI-2108, a first-in-class, ileocolonic-targeted PDE4 inhibitor prodrug, for the treatment of fibrostenotic Crohn's disease (FSCD). Topline data are anticipated in the first quarter of 2026.

"The initiation of patient dosing marks a significant milestone in our mission to address fibrostenotic complications in Crohn's disease, an area with no current approved medical therapies," said Dr. Mitchell Jones, Chief Medical Officer of Palisade Bio. "This mechanistic study is designed to generate critical insights into how PALI-2108 modulates inflammatory and fibrotic pathways in intestinal tissue. Together with data from our ulcerative colitis studies, these findings will inform our planned Phase 2 development and regulatory interactions in 2026."

The open-label, exploratory Phase 1b study will enroll approximately 6 to 12 patients with FSCD. The study is designed to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of once-daily oral dosing of PALI-2108 over a 14-day treatment period. PALI-2108 is a next-generation phosphodiesterase-4 (PDE4) inhibitor prodrug engineered for targeted activation in the terminal ileum and colon, designed to provide high local tissue exposure with minimal systemic absorption.

In addition to safety and PK/PD assessments, the study will evaluate tissue-level pharmacology and molecular responses using paired ileal biopsies and peripheral blood mononuclear cells (PBMCs). Analyses will include single-nucleus and single-cell RNA sequencing to characterize treatment-induced changes in inflammatory and fibrotic signaling. Exploratory endpoints include endoscopic, histologic, and intestinal ultrasound (IUS) measures to assess structural and inflammatory features of FSCD lesions.

Data from this study, together with results from the Phase 1a/1b ulcerative colitis (UC) program, are expected to support Phase 2 Investigational New Drug (IND) submissions to the U.S. Food and Drug Administration (FDA) in the first half of 2026.

About PALI-2108

PALI-2108 is an orally administered, prodrug engineered for local delivery of phosphodiesterase-4 (PDE4) inhibition to the terminal ileum and colon. The prodrug molecule is gut-restricted and pharmacologically inactive until it reaches the lower intestine, where it is cleaved by bacterial enzymes to release its active PDE4 inhibitor metabolite directly at the site of inflammation and fibrosis. This targeted and slow-release design prevents absorption through the upper gut, achieves sustained local exposure and a longer half-life that enables once-daily dosing, and is engineered to produce a blunted peak plasma concentration to improve the overall therapeutic index. Together, these properties are intended to maximize anti-inflammatory and anti-fibrotic effects while minimizing systemic exposure and reducing class-related tolerability issues, such as nausea and headache, that have limited systemic PDE4 inhibitors.

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 timing and results of clinical trials, the potential therapeutic benefits of PALI-2108, and plans for regulatory submissions. These forward-looking statements are based on the Company's current expectations. Forward-looking statements involve risks and uncertainties. Important factors that could cause actual results to differ materially from those reflected in the Company's forward-looking statements include, among others, the timing of enrollment, commencement and completion of the Company's clinical trials; the Company's reliance on PALI-2108, and its early stage of clinical development; the risk that prior results, such as signals of safety, activity, dosing or durability of effect, observed from preclinical or clinical trials, will not be replicated or will not continue in ongoing or future studies or clinical trials involving the Company's product candidates in clinical trials focused on the same or different indications; and other factors that are described in the "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations" sections of 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.

Investor Relations Contact

JTC Team, LLC

Jenene Thomas

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Source: Palisade Bio