Palisade Bio Reports Positive Topline Data from Phase 1b Clinical Study of PALI-2108 in Fibrostenotic Crohn's Disease

• PALI-2108 demonstrated favorable safety and tolerability with no serious adverse events after two weeks of treatment in a difficult-to-treat population
  
  
• Phase 1b data demonstrate endoscopic improvement, with a 47.5% reduction in SES-CD score and 40% of patients achieving endoscopic response and 40% of patients achieving endoscopic remission
  
  
• Pharmacokinetic and pharmacodynamic data from ileal tissue and plasma support once-daily oral dosing for Crohn’s disease showing IC90 coverage, with correlation to accepted inflammatory biomarkers
  
  
• Data support expansion into broader luminal CD, an indication that has regulatory clarity, more than doubles the total addressable patient population, and has no anatomical constraints
  
  
• Company plans to advance PALI-2108 into a Phase 2 trial in moderate to severe Crohn’s disease, including evaluation of anti-fibrotic effects earlier in the disease course
  
  
• Company to host webcast March 31^st at 8:00 AM ET – Access the webcast here
  
  

Carlsbad, CA, March 30, 2026 (GLOBE NEWSWIRE) -- Palisade Bio, Inc. (Nasdaq: PALI) (“Palisade” or the “Company”), a clinical-stage biopharmaceutical company developing next-generation, once-daily, oral PDE4 inhibitor prodrugs designed for targeted delivery to the ileum and colon, today announced positive topline data from its Phase 1b clinical study evaluating PALI-2108, a first-in-class, once-daily oral PDE4 inhibitor prodrug designed to be selectively bioactivated in the ileum and colon, in patients with fibrostenotic Crohn’s disease (FSCD).

This Phase 1b study demonstrated favorable safety and tolerability, robust pharmacodynamic target engagement in ileal tissue, and encouraging early signals of clinical activity in the five participating patients. These data support the continued development of PALI-2108 as a potential first therapy designed to address both inflammatory and fibrotic components of Crohn’s disease.

“These positive data represent an important step in advancing PALI-2108 as a potential first therapy designed to address fibrostenotic complications in Crohn’s disease,” said Mitch Jones, MD, Ph.D., President & Chief Medical Officer of Palisade Bio. “The favorable safety profile, robust ileal target engagement, and convergence of biomarker and endoscopic improvements reinforce the potential of our once-daily oral PDE4 inhibitor prodrug to modulate both inflammatory and fibrotic pathways. We believe these findings support continued development for Phase 2 in ulcerative colitis and luminal and fibrostenotic Crohn’s disease.”

Key Clinical Findings

• Safety and Tolerability
  • No serious adverse events (SAEs) reported
  • No clinically significant laboratory, vital sign, or EKG abnormalities observed
  • PALI-2108 was generally well tolerated across all patients
  • All adverse events were mild and self-limited; no PDE4 class-related adverse events (e.g., nausea, diarrhea, headache) observed
• Pharmacokinetics and Pharmacodynamics
  • Pharmacokinetic profile supported once-daily dosing with measurable systemic and tissue exposure; patients achieved plasma drug concentrations above IC90 by the end of titration with doses as low as 20 mg daily
  • Tissue levels were above IC90, and increased over plasma by ~3x in ileum and ~5x in colon by Day 14
  • Robust ileal pharmacodynamic activity demonstrated by a mean 41% increase in tissue cAMP, a key marker of PDE4 inhibition, with no decreases observed across patients
  • Ileal target engagement exceeded prior colonic cAMP responses observed in ulcerative colitis studies, supporting effective localized drug activation in the ileum
• Biomarkers and Translational Data
  • Mean fecal calprotectin (FCP) decreased by approximately 59% (268 ? 110 µg/g) after 14 days of treatment
  • Strong inverse correlation between ileal cAMP and FCP (r = ?0.92), linking target engagement with reduction in inflammatory burden
  • Plasma and tissue biomarker trends were consistent with modulation of inflammatory and fibrosis-related pathways
• Exploratory Clinical and Endoscopic Measures
  • Mean SES-CD improved by ?3.8 points (~47.5% reduction)
  • 40% of patients achieved endoscopic response and 40% achieved endoscopic remission
  • Convergent improvements observed across pharmacodynamic, biomarker, and endoscopic endpoints
    
    

In the context of published benchmarks, Week 12 endoscopic response rates of 29–40% and remission rates of 19–24% have been reported for risankizumab, and 34–46% and 19–30% for upadacitinib. While differences in trial design and timing preclude direct comparison, the early endoscopic improvements observed with PALI-2108 at Week 2 fall within these ranges.

“Fibrosis-related Crohn’s disease remains a significant unmet medical need, as current therapies primarily target inflammation but do not directly address the fibrotic components of the disease,” said Laurent Peyrin-Biroulet, M.D., Ph.D., Professor of Gastroenterology at the University of Lorraine and investigator in the study. “The results observed in this study are highly encouraging, demonstrating robust target engagement, reductions in inflammatory biomarkers, and meaningful early endoscopic improvements. These data are consistent with modulation of pathways involved in both inflammation and fibrosis. If confirmed in larger studies, this targeted approach has the potential to represent an important advance in the treatment of fibrostenotic and luminal Crohn’s disease.”

The Phase 1b study enrolled five patients with FSCD and confirmed ileal stenosis and was designed to evaluate safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of PALI-2108 following once-daily oral dosing over a 14-day treatment period. The study incorporated paired ileal biopsies and advanced molecular analyses, including cAMP quantification and RNA sequencing, to characterize treatment-induced changes in inflammatory and fibrotic signaling pathways. For more information about the Phase 1a/b clinical study, visit clinicaltrials.gov and reference identifier NCT07428096.

The positive results from the trial support the continued development of PALI-2108, and the Company plans to initiate a Phase 2 study in a moderate to severe Crohn’s disease population. In addition to evaluating clinical remission, response, and pharmacodynamic biomarkers over 12 weeks, the study will also assess anti-fibrotic effects earlier in the disease course.

These topline data will be presented by the Company’s President and Chief Medical Officer, Mitch Jones, MD, Ph.D., at the 4^th Annual Precision Medicine in IBD Summit in Boston, MA. The talk titled, “Targeted PDE4 Inhibition Using PALI-2108 Prodrug as a Novel Therapeutic Strategy in Fibrostenotic Crohn’s Disease,” is scheduled for Wednesday, April 1, 2026 at 9:30 AM ET. The full data set is expected to be presented at future leading medical conferences.

Conference Call and Webcast

Palisade Bio management will host a conference call and webcast for investors, analysts, and other interested parties tomorrow, March 31, 2026 at 8:00 AM ET.

Interested participants and investors may access the conference call by dialing (877) 869-3847 (domestic) or (201) 689-8261 (international) and referencing the Palisade Bio Conference Call. The live audio webcast will be accessible on the Events page of the Investors section of the Palisade Bio website, palisadebio.com, and will be archived for 90 days.

About Palisade Bio

Palisade Bio, Inc. (Nasdaq: PALI) (“Palisade” or the “Company”) is a clinical-stage biopharmaceutical company advancing a next generation oral PDE4 inhibitor prodrugs designed to improve pharmacology, tolerability and convenience for patients with inflammatory and fibrotic diseases. Through its differentiated prodrug platform and precision pharmacology strategy, Palisade Bio is committed to transforming proven PDE4 biology into better, safer oral therapies for patients living with chronic inflammatory and fibrotic diseases.

The Company’s lead program, PALI-2108, is a once-daily oral PDE4 inhibitor prodrug designed to be selectively bioactivated in the ileum and colon, initiating targeted PDE4 inhibition at sites of disease while enabling systemic distribution of the active drug.

Palisade Bio is now advancing towards a Phase 2 clinical study in UC designed to evaluate clinical remission, response and pharmacodynamic biomarkers over 12 weeks, with an extension phase assessing maintenance of remission. 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 mechanisms of action and 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, clinical response, dosing or durability of effect, observed from preclinical or clinical trials with a limited number of patients, 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, 2025, filed with the Securities and Exchange Commission (“SEC”) on March 20, 2026, 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
908-824-0775
PALI@jtcir.com