Palisade Bio Announces First Patient Dosed in Global Phase 2b ASCENTRA-UC Study Evaluating Once-Daily Oral PALI-2108 for the Treatment of Ulcerative Colitis

PALI-2108 is an investigational, gut-activated, once-daily oral PDE4 inhibitor prodrug designed for sustained exposure and anti-inflammatory activity with the potential to improve tolerability

29 of 30 planned U.S. sites already activated

Global expansion progressing toward ~115 total sites, with CTA clearance in Canada and submissions under review in Europe and other international countries

12-week induction topline results expected Q4 2027

Denver, CO, Oct. 28, 2026 (GLOBE NEWSWIRE) -- Palisade Bio, Inc. (Nasdaq: PALI) (“Palisade” or the “Company”), a clinical-stage biopharmaceutical company developing oral therapies for immune-mediated and fibrotic diseases, today announced that the first patient has been dosed in ASCENTRA-UC, its global Phase 2b clinical trial evaluating PALI-2108 in approximately 204 patients with moderately to severely active ulcerative colitis (UC).

“Dosing the first patient in ASCENTRA-UC represents an important milestone for Palisade and for people living with ulcerative colitis, many of whom still lack durable, well-tolerated oral treatment options,” said JD Finley, Chief Executive Officer of Palisade Bio. “We believe PDE4 inhibition remains a compelling anti-inflammatory and anti-fibrotic mechanism. PALI-2108’s prodrug design is intended to address historical tolerability limitations associated with this class. Our goal is to develop a once-daily oral therapy that can deliver meaningful disease control on its own, with longer-term potential in combination with therapies targeting complementary pathways. With U.S. enrollment underway and global expansion progressing, we look forward to reporting topline induction results in the fourth quarter of 2027.”

PALI-2108 is an investigational, once-daily oral PDE4 inhibitor prodrug designed for targeted bioactivation in the terminal ileum and colon. Its pharmacologic profile is intended to provide high intestinal tissue exposure and sustained systemic exposure while potentially mitigating tolerability limitations historically associated with systemic PDE4 inhibition. In the completed Phase 1 program, PALI-2108 was generally well tolerated with no serious adverse events reported and showed pharmacokinetic and pharmacodynamic findings supportive of further development. In a small, open-label, exploratory Phase 1b UC cohort of five enrolled patients treated for seven days, all five evaluable patients achieved clinical response and two achieved clinical remission based on the modified Mayo Score. These preliminary, uncontrolled findings support further evaluation in the randomized, placebo-controlled ASCENTRA-UC study. The Company has activated 29 of 30 planned U.S. sites and is advancing site start-up in Canada and other international countries.

“ASCENTRA-UC is designed to rigorously evaluate the efficacy and safety of PALI-2108 across two once-daily oral dose levels, with clinical remission at Week 12 as the primary endpoint,” said Mitch Jones, M.D., Ph.D., President and Chief Medical Officer of Palisade Bio. “The study will also assess clinical response, endoscopic improvement and histologic-endoscopic mucosal improvement, along with the durability of treatment response. Our Phase 1 findings showed early signals of clinical activity, sustained exposure of the active metabolite, and pharmacodynamic evidence of PDE4 pathway modulation. Clinical site activation is, as of now, ahead of schedule, with substantially all U.S. sites now activated. We look forward to determining whether these findings translate into meaningful clinical benefit in a larger, controlled patient population.”

ASCENTRA-UC is a global, multicenter, randomized, double-blind, placebo-controlled, dose-ranging Phase 2b clinical trial designed to evaluate the efficacy, safety, pharmacokinetics and pharmacodynamics of PALI-2108 in patients with moderately to severely active ulcerative colitis. The study is expected to enroll approximately 204 patients and evaluate two once-daily dose levels of PALI-2108, 15 mg and 30 mg, compared with placebo. The primary endpoint is clinical remission at Week 12, as measured by the Modified Mayo Score. Key secondary endpoints include clinical response, endoscopic improvement and histologic-endoscopic mucosal improvement (HEMI). Following the 12-week induction period, eligible patients will continue into a 36-week maintenance phase designed to evaluate the durability of response through Week 48.

Primary efficacy results from the 12-week induction period are expected in the fourth quarter of 2027.

PALI-2108 is an investigational oral PDE4 inhibitor prodrug designed for localized bioactivation in the terminal ileum and colon and being developed for once-daily dosing. Its active metabolite, PALI-0008, potently inhibits PDE4 isoforms A, B and D, increasing intracellular cAMP to modulate inflammatory signaling. Phase 1 studies have provided evidence of high intestinal exposure, sustained systemic exposure, favorable short-term tolerability and early clinical activity, supporting Phase 2 development in UC and Crohn’s disease. PALI-2108 has not been approved for any indication.

Palisade Bio is a clinical-stage biopharmaceutical company developing oral therapies for immune-mediated and fibrotic diseases. Its lead program, PALI-2108, is in Phase 2 development in ulcerative colitis, with a Phase 2 study in Crohn’s disease underway.

For more information, please go to www.palisadebio.com.

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. Words such as “anticipate,” “believe,” “designed to,” “expect,” “goal,” “intend,” “may,” “plan,” “potential,” “will” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Forward-looking statements include but are not limited to: implied or express statements regarding the pharmacological properties, safety, tolerability, clinical response and efficacy, and therapeutic potential of PALI-2108, dosing levels and timing of key PALI-2108 development milestones such as regulatory submissions and approvals, trial enrollments and commencements and efficacy readouts; the design, conduct, enrollment and expected timing of results of the ASCENTRA-UC trial, including site activation and the expansion of the trial outside the United States; the potential of PALI-2108 to improve tolerability relative to other PDE4 inhibitors; plans to develop PALI-2108 in Crohn’s disease; and the Company’s expected cash runway. 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 Company’s ability to activate clinical sites on the anticipated timeline; the timing and outcome of regulatory reviews of clinical trial applications outside the United States; the Company’s reliance on third parties, including contract research organizations and clinical sites; the risk that prior results, such as signals of safety, clinical response and efficacy, 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; the risk that safety or tolerability findings emerge in larger, controlled studies; the Company’s need for additional capital to complete its clinical development programs; 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, except as required by law.