PALI-2108 demonstrated to be safe and well tolerated with no serious adverse events (SAEs)
Extended half-life and local bioactivation support convenient once-daily dosing in ulcerative colitis (UC) and fibrostenotic Crohn's disease (FSCD)
Colon tissue drug levels exceeded target thresholds 36 hours post-dose in completed Phase 1a MAD cohort
Company advancing toward IND submission for Phase 2 study in H1 2026
Carlsbad, CA, Aug. 07, 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 compelling new data from its ongoing clinical program evaluating PALI-2108, a first-in-class, ileocolonic-targeted PDE4 inhibitor, including positive topline results from its Phase 1b open-label cohort in patients with moderate-to-severe UC and colon tissue pharmacokinetic (PK) data from the Phase 1a multiple ascending dose (MAD) cohort.
"These results represent a significant milestone for PALI-2108," said JD Finley, Chief Executive Officer of Palisade Bio. "The early clinical activity, targeted delivery, dose flexibility, the potential for once-daily oral dosing and its favorable safety profile positions PALI-2108 as a potentially best-in-class oral therapy for patients with UC."
Dr. Mitchell Jones, Chief Medical Officer added, "What is most compelling about the Phase 1b data is the remarkable consistency across all layers of assessment. The clinical response rate of 100% was tightly aligned with robust histologic improvements and a marked reduction in tissue lymphocytes-reflecting immunologic resolution. These effects were mechanistically supported by increased tissue cAMP levels and decreased PDE4B expression, confirming potent local target engagement. Additionally, RNA sequencing demonstrated coordinated downregulation across our inflammatory biomarker panel, fibrotic markers, PDE4 effector genes, and our companion diagnostic biomarker score, reinforcing both the breadth of pharmacodynamic activity and the precision medicine potential of PALI-2108."
Phase 1b UC Cohort: 100% Clinical Response with Strong Biomarker and Histology Improvements
The 7-day, open-label Phase 1b study enrolled five patients with moderate-to-severe UC, receiving titrated BID dosing of PALI-2108 (30 mg BID). Key highlights include:
- Achieved 100% (5/5) clinical response (=30% or =3-point reduction in modified Mayo score with rectal bleeding subscore =1)
- Mean reduction of 62.8% in modified Mayo score (-4.0 point absolute change)
- One patient achieved clinical remission
- Fecal calprotectin decreased in 4/5 patients (mean 70%)
- Plasma hsCRP decreased by 15%
- Showed histologic improvement across multiple indices:
- Nancy Index: 58%
- Robarts Histopathology Index: 56%
- Geboes Score: 36%
Mechanistically, colon tissue analyses confirmed PDE4 inhibition and immunomodulation:
- Tissue cAMP increased in 4/5 patients
- Tissue lymphocytes decreased by an average of 40%
- PDE4B expression decreased by an average of 51%
- RNAseq data confirmed downregulation of inflammatory, fibrotic, and CDx biomarkers from baseline to end-of-study
Importantly, PALI-2108 was well tolerated, with >95% of treatment-emergent adverse events (TEAEs) rated mild and transient (e.g., headache, nausea), and no SAEs, SUSARs (suspected unexpected adverse reactions), or discontinuations.
Phase 1a MAD Cohort: Colon Tissue Drug Concentrations Confirm Extended Exposure and Once-Daily Dosing
In parallel, Palisade Bio completed a comprehensive Phase 1a study in 84 healthy volunteers across SAD, MAD, and food-effect cohorts. Key results include:
- The PDE4 inhibitor active metabolite (PALI-0008) remained detectable in colon tissue =36 hours post-dose, maintaining levels near or above IC90
- Steady-state trough concentrations exceeded IC90 with minimal accumulation
- Half-life of PALI-0008 exceeded that of any known PDE4 inhibitor, supporting sustained local activity
- PK modeling supports a once-daily dose regimen of 30 mg for both UC and FSCD
- Food reduced systemic exposure (~42% ? Cmax, ~20% ? AUC) but improved tolerability
- No SAEs or dose-limiting toxicities reported; >95% of TEAEs were mild and self-limited
Based on these findings, Palisade Bio plans to complete a Phase 1b study in patients with fibrostenotic Crohn's disease by the second half of 2025. The Company's previously completed Phase 1a and 1b studies in ulcerative colitis, along with the upcoming FSCD study, will form the foundation for submitting a Phase 2 Investigational New Drug (IND) application and clinical protocols to the U.S. Food and Drug Administration (FDA) in the first half of 2026.
For more information about the Phase 1a/b clinical study, visit clinicaltrials.gov and reference identifier NCT06663605.
About PALI-2108
PALI-2108 is an orally administered prodrug engineered to deliver PDE4 inhibition selectively to the distal ileum and colon. The compound leverages a microbiome-activated mechanism to achieve regional bioactivation, minimize systemic exposure, and optimize mucosal tissue concentration. This localized approach reduces class-associated side effects while preserving anti-inflammatory and anti-fibrotic activity-a unique and clinically validated therapeutic strategy.
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, potential clinical efficacy 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 be a first-in-class and best-in-class therapy; and the expected timing of the Company's planned Phase 2 clinical studies. 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, 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
PALI@jtcir.com
