Palisade Bio Reports Positive Phase 1a Results for PALI-2108, a First-in-Class Terminal Ileum and Colon-Targeted PDE4 B/D Inhibitor for Fibrostenotic Crohn’s Disease and Ulcerative Colitis

Rhea-AI Summary

Palisade Bio (NASDAQ: PALI) announced positive Phase 1a results for PALI-2108, their novel terminal ileum and colon-targeted PDE4 B/D inhibitor for fibrostenotic Crohn's disease and ulcerative colitis. The study successfully met its primary endpoints, demonstrating favorable safety, tolerability, and pharmacokinetics. Key findings include: no serious adverse events across SAD/MAD cohorts, only mild reversible TEAEs at higher doses, and confirmation of the drug's targeted delivery profile. PK analysis showed therapeutically relevant concentrations in colon tissue for up to 24 hours post-dose with low systemic exposure. Based on these results, Palisade Bio plans to initiate a Phase 1b cohort in fibrostenotic Crohn's disease patients while preparing for Phase 2 clinical programs.

Positive

• Study met all primary endpoints for safety, tolerability, and pharmacokinetics
• No serious adverse events (SAEs) observed across SAD/MAD cohorts
• PK analysis confirmed therapeutic concentrations in colon tissue up to 24 hours post-dose
• 15mg BID dose showed no treatment-emergent adverse events
• Data supports advancement to Phase 2 development

Negative

• Moderate adverse event at 50mg BID dose led to patient withdrawal
• Some mild and reversible treatment-emergent adverse events occurred at highest doses
• Food intake showed modest impact on drug absorption timing and concentration

Insights

Pharmaceutical Clinical Development Expert

Palisade Bio's PALI-2108 shows promising Phase 1 safety profile with targeted colon delivery, advancing to Phase 2 for Crohn's and UC.

The Phase 1 results for PALI-2108 represent a significant milestone in Palisade Bio's clinical development program. The drug successfully achieved its primary endpoints of safety, tolerability, and pharmacokinetics across single ascending dose, multiple ascending dose, and food effect studies. What's particularly noteworthy is the absence of serious adverse events or laboratory/EKG-related adverse events across all study cohorts, which is encouraging for a PDE4 inhibitor, a class that historically has been associated with systemic side effects.

The pharmacokinetic data provides compelling evidence that PALI-2108's targeted prodrug design is working as intended. The drug demonstrated therapeutic concentrations in colon tissue for up to 24 hours post-dose while maintaining low systemic exposure. This localized activation in the distal gut is crucial for minimizing off-target effects while maximizing therapeutic benefit where it's needed most—in the terminal ileum and colon, the primary sites affected in Crohn's disease and ulcerative colitis.

The dose-dependent relationship observed with Cmax and AUC increasing proportionally with dosage provides clear parameters for future clinical trials. Of particular interest is the 15mg BID dose, which was free of any treatment-emergent adverse events, and the 30mg BID titrated dose that showed minimal side effects that resolved quickly. These findings suggest a potential sweet spot for balancing efficacy and tolerability.

For a first-in-class terminal ileum and colon-targeted PDE4 B/D inhibitor, these results represent a promising start. While Phase 1 studies primarily assess safety rather than efficacy, the achievement of therapeutic concentrations in target tissues suggests potential clinical benefit. The company's planned progression to a Phase 1b cohort in fibrostenotic Crohn's disease patients, followed by Phase 2 studies, will be critical in determining whether this targeted approach can address the significant unmet need in inflammatory bowel disease, particularly for patients with fibrostenotic complications that often require surgical intervention.

Study met its primary endpoints of safety, tolerability, and pharmacokinetics (PK) 

No serious adverse events (SAEs) or treatment-emergent adverse events (TEAEs) related to laboratory values or EKGs observed across SAD/MAD cohorts

Management releases a “What This Means” segment discussing the topline Phase 1a data; Access here

Carlsbad, CA, May 27, 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 positive topline results from its completed Phase 1 studies of PALI-2108, a novel, locally-activated, terminal ileum and colon-targeted phosphodiesterase-4 B/D (PDE4 B/D) inhibitor being developed for fibrostenotic Crohn’s disease (FSCD) and moderate to severe ulcerative colitis (UC). Additionally, the Company announced the release of a Virtual Investor “What This Means” segment to discuss the topline data, which is now available here.

The Phase 1 program, which included single ascending dose (SAD), multiple ascending dose (MAD), and cross-over food effect (FE) studies in adult healthy volunteers, as well as a small cohort of UC patients, successfully met its primary endpoints of safety, tolerability, and pharmacokinetics (PK). The data support progression into Phase 2 development.

“These data validate PALI-2108’s targeted prodrug design and provide compelling evidence that the drug reaches therapeutic concentrations in the colon with lower systemic exposure,” said Dr. Mitchell Jones, Chief Medical Officer of Palisade Bio. “The observed tissue penetration of the active drug and the absence of serious adverse events, together with our significant body of nonclinical PK data, support our confidence in advancing PALI-2108 into patient-focused trials for fibrostenotic Crohn’s disease and ulcerative colitis.”

Key Phase 1 Findings

• Safety & Tolerability:
  
  
  • No serious adverse events (SAEs) or laboratory/EKG-related adverse events were observed across SAD, MAD and FE cohorts.
    
  • In the SAD study (15–450 mg), only mild and reversible treatment-emergent AEs (TEAEs) occurred, limited to the highest dose (450 mg).
  • MAD cohorts (15, 30, and 50 mg BID over 7 days, as well as 30 mg titrated over 7 days) showed mostly minor TEAEs and most often at higher doses, with a moderate event at 50 mg BID leading to withdrawal. Importantly the 15 mg BID dose was free of any TEAEs and the 30mg BID titrated dose had one minor TEAE that resolved within the first days of the study.
    
    
• Pharmacokinetics:
  
  
  • PK analysis confirmed the delayed-release, terminal ileum-targeted and colon-targeted profile of PALI-2108.
    
  • Plasma and tissue PK demonstrated that therapeutically relevant concentrations (above estimated IC₅₀) were achieved in colon tissue up to 24 hours post-dose.
  • Plasma-to-tissue ratios confirmed localized drug activation in the distal gut with low systemic exposure.
  • Cmax and AUC increased roughly proportionally with dose; food intake modestly delayed Tmax and modestly reduced Cmax, consistent with the prodrug’s intended release profile.

• Modeling and Dosing:
  
  
  • Population PK modeling and dose-exposure simulations support a therapeutic window aligned with the safety and tolerability observed in Phase 1.
    
  • The data support continued dose exploration in future clinical trials.

“The pharmacokinetic and safety data are highly encouraging, particularly the tissue exposure levels in colon biopsies,” added Dr. Gaetano Morelli, Principal Investigator of the Phase 1 study and clinical gastroenterologist. “This targeted approach could address a critical gap in treatment for patients with fibrostenotic disease and could reduce risks associated with systemic PDE4 inhibition.”

Based on these results, Palisade Bio plans to initiate an additional safety and tolerability and PK/PD exploration Phase 1b cohort in FSCD while completing longer-term chronic safety and toxicology studies, to be followed closely by initiating Phase 2 clinical programs to assess PALI-2108’s efficacy, safety, and tolerability in patients with FSCD as well as those with moderate to severe UC. The planned Phase 1b cohort is expected to evaluate multiple dosing strategies to define optimal therapeutic exposure and patient response and the planned Phase 2 studies are expected to evaluate clinically meaningful endpoints for the patients with FSCD and 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 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. 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 timing and success of preclinical studies and clinical trials conducted by the Company, the risk that prior results, such as signals of safety, activity, 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
908-824-0775
PALI@jtcir.com

FAQ

What were the main results of PALI's Phase 1a trial for PALI-2108?

The Phase 1a trial met all primary endpoints, showing favorable safety, tolerability, and pharmacokinetics. No serious adverse events were observed, and the drug achieved therapeutic concentrations in colon tissue with low systemic exposure.

What is PALI-2108 being developed to treat?

PALI-2108 is being developed to treat fibrostenotic Crohn's disease (FSCD) and moderate to severe ulcerative colitis (UC).

Were there any significant side effects in Palisade Bio's PALI-2108 trial?

Only mild and reversible treatment-emergent adverse events occurred at the highest doses (450mg), with one moderate event at 50mg BID leading to withdrawal. The 15mg BID dose showed no adverse events.

What are the next steps for PALI-2108's clinical development?

Palisade Bio plans to initiate a Phase 1b cohort in FSCD patients while completing long-term safety studies, followed by Phase 2 clinical programs for both FSCD and UC patients.

How does PALI-2108 work in treating inflammatory bowel diseases?

PALI-2108 is a locally-activated, terminal ileum and colon-targeted PDE4 B/D inhibitor that achieves therapeutic concentrations in the colon with lower systemic exposure through its targeted prodrug design.