Palisade Bio Reports Positive PALI-2108 Phase 1b Clinical Data
PALI-2108 demonstrated favorable safety, with no serious adverse events, lab abnormalities, or EKG concerns
Phase 1b data demonstrated 100% clinical response and promising signals regarding the efficacy of PALI-2108 in ulcerative colitis (UC) using FDA-defined endpoints
Biomarker analyses showed normalization of 186 genes linked to fibrosis and Crohn's disease strictures, supporting translational potential in fibrostenotic Crohn's disease (FSCD)
Patient dosing in the Phase 1b FSCD study is expected to begin in 2H 2025; Phase 2 IND submissions anticipated in 1H 2026
Carlsbad, CA, Sept. 17, 2025 (GLOBE NEWSWIRE) -- Palisade Bio, Inc. (NASDAQ:PALI) ("Palisade," "Palisade Bio," or the "Company"), a clinical-stage biopharmaceutical company developing precision therapies for autoimmune, inflammatory, and fibrotic diseases, today announced new data from its ongoing clinical program evaluating PALI-2108, a first-in-class, ileocolonic-targeted PDE4 B/D inhibitor. The results are to be presented in an oral session at the STAR Consortium Annual Meeting – the accompanying slides are now available here.
The Phase 1b UC cohort demonstrated rapid and consistent clinical activity, with all patients responding to treatment. While the study was shorter in duration than standard induction trials and not powered for efficacy, there was promising signals of clinical improvement, with 2 of 5 patients achieving remission after only seven days. These improvements were reinforced by favorable histology and biomarker changes that confirmed local PDE4 engagement and broad immunologic resolution. Together with the strong safety and PK profile observed in the Phase 1a study, the results highlight PALI-2108's differentiated potential as both an anti-inflammatory and anti-fibrotic therapy.
"These results highlight the differentiated profile of PALI-2108, demonstrating strong safety, rapid clinical activity, and broad biomarker engagement in ulcerative colitis, while reinforcing its potential as the first targeted anti-fibrotic therapy in Crohn's strictures," said JD Finley, Chief Executive Officer of Palisade Bio. "We are excited to advance this program into its next stage of development as we prepare for Phase 2."
Key Clinical Findings
Phase 1a Safety and Pharmacokinetics (n=84, SAD/MAD)
- No serious adverse events (SAEs) and no lab or EKG abnormalities observed.
- Well tolerated at single doses up to 450 mg and multiple BID doses up to 50 mg.
- Extended half-life and colon-targeted bioactivation support once-daily dosing.
Phase 1b Ulcerative Colitis (UC) Cohort (n=5, 7 days)
- All patients (5/5 patients) showed a clinical response as measured by modified Mayo score
- Two of the 5 patients achieved clinical remission based on FDA-defined endpoints
- 62.8% mean reduction in modified Mayo score (~4-point absolute decrease)
- Histologic improvements: Nancy Index ↓58%, Robarts Index ↓56%, Geboes Score ↓36%
- Inflammatory biomarkers reduced: fecal calprotectin ↓~70%, hsCRP ↓~15%
- Mechanistic biomarkers improved: colon tissue cAMP ↑~27%, tissue lymphocytes ↓~29%, tissue PDE4B ↓~71%
Translational Relevance to FSCD
- 186 fibrotic gene markers elevated at baseline in UC patients were reduced at endpoint.
- Data support anti-fibrotic potential of PALI-2108 in FSCD.
Dr. Mitchell Jones, Chief Medical Officer, added, "What stands out is the consistency across clinical, histologic and mechanistic readouts in UC. The rapid clinical responses and biomarker improvements we observed support PALI-2108's targeted engagement of PDE4 biology and reinforce its potential to become a best-in-class oral therapy for UC. Importantly, the same mechanistic pathways also support anti-fibrotic activity, which we believe extends the opportunity into FSCD. By advancing UC as our lead indication, we are prioritizing a clear regulatory and clinical path while maintaining the broader potential of this program."
For more information about the Phase 1a/b clinical study, visit clinicaltrials.gov and reference identifier NCT06663605. Data from the planned Phase 1b FSCD study, together with results from Palisade's completed Phase 1a/1b trials in UC, will support the Company's planned Phase 2 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 gut-restricted delivery of PDE4 B/D inhibition to the terminal ileum and colon. Activated by bacterial enzymes in the lower intestine, PALI-2108 achieves high local tissue concentrations while minimizing systemic exposure. This design aims to maximize anti-inflammatory and anti-fibrotic effects while reducing class-related tolerability issues such as nausea and headache that have historically 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 safety and tolerability, PK and drug release characteristics, clinical response and clinical efficacy rates and dosing requirements of PALI-2108 based on the Company's preclinical studies and data from its Phase 1a/b clinical study; indications and anticipated benefits of PALI-2108, including the potential of PALI-2108 to treat FSCD; and the expected timing of the Company's planned Phase 1b clinical study of PALI-2108 for the treatment of FSCD and the planned Phase 2 clinical study of PALI-2108 for the treatment of UC. 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, clinical efficacy, 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; the Company's ability to secure additional financing to fund future operations and development of its product candidates; 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
908-824-0775
[email protected]
Source: Palisade Bio
