Palisade Bio Presents Positive Preclinical Data of PALI-2108 for the Treatment of Ulcerative Colitis

Rhea-AI Summary

Palisade Bio (NASDAQ: PALI) presented positive preclinical data for PALI-2108, their oral colon-specific PDE4 inhibitor prodrug for ulcerative colitis treatment, at the 2025 Crohn's and Colitis Congress. The drug demonstrated effectiveness in reducing colitis symptoms in mice without CNS toxicity.

Key findings showed that PALI-2108 effectively converts to the active PDE4 inhibitor PALI-0008 in the colon following oral administration in mice, dogs, and humans. The drug outperformed standard treatments in preclinical studies, showing superior potency and target engagement compared to other PDE4 inhibitors.

The company is currently conducting a Phase 1a/b clinical study (NCT06663605) evaluating safety, tolerability, and pharmacokinetics in healthy volunteers and UC patients. Topline data is expected in the first half of 2025.

Positive

• Demonstrated superior efficacy compared to standard treatments in preclinical studies
• Showed favorable safety profile with no systemic toxicity issues in animal studies
• Successfully converts to active form in colon tissue across multiple species
• Phase 1a/b trial progressing with positive safety profile in single-ascending-dose cohorts

Negative

• Still in early clinical development phase with no proven human efficacy yet
• Requires twice-daily dosing during induction phase

Insights

Medical Research Analyst

The preclinical data for PALI-2108 represents a significant advancement in ulcerative colitis treatment development. The drug's colon-specific activation mechanism addresses a important limitation of current PDE4 inhibitors - systemic exposure leading to CNS side effects. This targeted approach could potentially provide a superior safety profile while maintaining therapeutic efficacy.

The comparative data showing PALI-2108 outperforming tacrolimus and apremilast is particularly noteworthy. The demonstrated superior potency and target engagement suggest a potential breakthrough in UC treatment, especially considering the favorable tissue-to-plasma ratios. The pharmacokinetic profile supporting both once-daily maintenance and twice-daily induction dosing provides flexibility in treatment protocols, which could enhance patient compliance.

The ongoing Phase 1a/b trial design is robust, incorporating both healthy volunteers and UC patients. This dual-approach strategy allows for comprehensive safety assessment while gathering early efficacy signals. The favorable safety profile observed in single-ascending-dose cohorts is encouraging, though it's important to note that broader safety data from multiple-ascending-dose cohorts will be important for full evaluation.

The market opportunity is substantial, as current UC treatments often face limitations in efficacy or safety. PALI-2108's potential to offer a safer, orally-administered option with targeted colonic delivery could position it favorably in the competitive landscape. However, success will ultimately depend on Phase 1a/b topline data expected in H1 2025, which will provide critical insights into the drug's clinical potential.

Data presented at the 2025 Crohn’s and Colitis Congress 

PALI-2108 demonstrated to effectively reduce colitis symptoms in DSS mouse model without CNS toxicity associated with systemic exposure

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

Carlsbad, CA, Feb. 10, 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 is in development for patients with ulcerative colitis (UC).

Palisade Bio presented a poster titled “PALI-2108, a Colon-Specific PDE4B Inhibitor Prodrug, Reduces Ulcerative Colitis Symptoms in an Acute Colitis DSS Mouse Model” at the Crohn’s & Colitis Congress in San Francisco, CA. The poster is available on the Company’s website.

“UC patients need new oral therapies with higher remission rates, less systemic immunosuppression, and a strong safety profile. We continue to be encouraged by our preclinical and clinical results for PALI-2108, and we believe PALI-2108 could be an important option for these patients,” said Mitch Jones, MD, Ph.D., Chief Medical Officer of Palisade Bio. “We are on track to report topline data in the first half of 2025 and are excited to continue exploring this novel, oral, intestinally activated PDE4 inhibitor.”

In the studies, mice with induced colitis were treated with PALI-2108 twice daily for three days. Plasma, duodenum, ileum, and colon samples were collected to measure drug levels, and a Cellular Thermal Shift Assay (CETSA) was used to assess PDE4 binding in colon tissue. In an acute colitis model, PALI-2108 was shown to reduce disease activity compared to tacrolimus and apremilast.

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

Key Highlights:

• PALI-2108 reduced colitis symptoms in mice without causing CNS toxicity, suggesting it could be a novel treatment for UC.
• It effectively converts to the active PDE4 inhibitor, PALI-0008, in the colon following oral administration in mice, dogs, and humans.
• PALI-2108 showed superior potency and target engagement in preclinical studies compared to other PDE4 inhibitors.
• It demonstrated dose-dependent efficacy in a mouse UC model, outperforming standard treatments.
• No systemic safety issues were observed in mice, dogs, or monkeys.
• PK modeling supports twice-daily dosing during induction and once-daily during maintenance, leveraging the drug’s extended-release properties.
• PALI-2108 exhibited a favorable therapeutic window, with higher tissue-to-plasma ratios and enhanced tissue inhibition in preclinical studies compared to other PDE4 inhibitors.
  

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 SAD portion of 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, 2023, filed with the Securities and Exchange Commission (“SEC”) on March 26, 2024, 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

FAQ

What are the key findings from PALI-2108's preclinical studies for ulcerative colitis?

PALI-2108 demonstrated reduced colitis symptoms in mice without CNS toxicity, showed superior potency compared to other PDE4 inhibitors, and effectively converted to its active form (PALI-0008) in the colon of mice, dogs, and humans.

When will Palisade Bio (PALI) release topline data for PALI-2108's Phase 1a/b trial?

Palisade Bio expects to report topline data from the Phase 1a/b trial of PALI-2108 in the first half of 2025.

What is the dosing regimen proposed for PALI-2108 in ulcerative colitis treatment?

The pharmacokinetic modeling supports twice-daily dosing during the induction phase and once-daily dosing during the maintenance phase.

How does PALI-2108 compare to existing ulcerative colitis treatments in preclinical studies?

In preclinical studies, PALI-2108 demonstrated superior efficacy in reducing disease activity compared to established treatments like tacrolimus and apremilast.

What is the current development status of PALI-2108 (PALI stock)?

PALI-2108 is currently in a Phase 1a/b clinical trial (NCT06663605) evaluating safety, tolerability, pharmacokinetics, and pharmacodynamics in both healthy volunteers and ulcerative colitis patients.