Palisade Bio Reports Rapid Clinical, Histologic and New Mechanistic Colon Tissue RNA Sequencing Data Supporting Targeted Activity of PALI-2108 at ECCO 2026

Rhea-AI Summary

Palisade Bio (Nasdaq: PALI) presented Phase 1b translational data for PALI-2108 at ECCO 2026 showing rapid, colon‑targeted activity. Key findings included measurable clinical response within seven days, localized suppression of inflammatory and fibrotic gene programs in colon tissue, reduced PDE4B expression with increased tissue cAMP, and an encouraging safety profile across 89 subjects. Analyses showed downregulation of TNF-α, JAK–STAT, NF-κB, MAPK and TGF-β signaling and reduced inflammatory cell signatures, while peripheral immune profiles remained largely unchanged, supporting a colon‑focused pharmacologic effect.

Positive

• 100% clinical response in Phase 1b cohort within seven days
• 40% clinical remission rate in Phase 1b cohort
• Localized colon target engagement with reduced PDE4B expression
• Increased colon tissue cAMP consistent with PDE4 inhibition
• Broad suppression of key inflammatory pathways (TNF, JAK‑STAT, NF‑κB, MAPK, TGF‑β)
• No ulcerative colitis patient discontinuations in Phase 1b

Negative

• Very small Phase 1b cohort (n=5) limits statistical confidence
• Short seven‑day treatment duration limits durability assessment
• Late‑stage efficacy and longer‑term safety data not yet available

Key Figures

Subjects in safety dataset: 89 subjects Phase 1b UC patients: 5 adults Treatment duration: 7 days +5 more

8 metrics

Subjects in safety dataset 89 subjects Encouraging safety profile across 89 subjects

Phase 1b UC patients 5 adults Phase 1b cohort with moderate-to-severe ulcerative colitis

Treatment duration 7 days PALI-2108 titrated for seven days in Phase 1b cohort

Clinical response rate 100% UC Phase 1b cohort achieved clinical response by modified Mayo Score

Clinical remission rate 40% UC Phase 1b cohort achieved clinical remission by modified Mayo Score

Healthy volunteers 84 volunteers No serious adverse events across 84 normal healthy volunteers

ECCO congress edition 21st Congress Data presented at 21st Congress of the European Crohn’s and Colitis Organization

S-3 listed shares 988,872 shares Shares listed in S-3 shelf registration filed August 15, 2025

Market Reality Check

Price: $1.61 Vol: Volume 2,254,840 is below...

low vol

$1.61 Last Close

Volume Volume 2,254,840 is below the 20-day average of 3,595,385, suggesting no outsized pre-news positioning. low

Technical Price $1.60 is trading above the 200-day MA at $1.30, despite being 39.39% below the 52-week high.

Peers on Argus

PALI is down 1.84% while scanner-flagged peers ADTX, GRI, and KTTA show gains of...

3 Up

PALI is down 1.84% while scanner-flagged peers ADTX, GRI, and KTTA show gains of about 4–7%. This divergence and lack of same-direction momentum indicate today’s setup is stock-specific rather than a sector-wide move.

Historical Context

5 past events · Latest: Feb 17 (Positive)

Pattern 5 events

Date	Event	Sentiment	Move	Catalyst
Feb 17	Advisory board addition	Positive	-1.7%	Added global IBD precision medicine leader to Clinical Advisory Board for PALI-2108.
Feb 09	Conference participation	Positive	+4.9%	Announced Piper Sandler immunology symposium fireside chat and investor meetings.
Feb 05	Conference presentation	Positive	-5.1%	Scheduled virtual presentation at Oppenheimer healthcare life sciences conference.
Jan 29	Advisory board additions	Positive	-3.6%	Appointed leading global IBD experts to support PALI-2108 Phase 2 strategy.
Jan 16	Poster selections	Positive	-5.1%	Two PALI-2108 abstracts selected for major inflammatory bowel disease conferences.

Pattern Detected

Recent PALI headlines are mostly positive (advisory board additions, conference/poster news), yet 4 of 5 prior events saw negative next-day reactions, suggesting a pattern of selling into good news.

Recent Company History

Over the last few months, Palisade Bio has focused on advancing PALI-2108, adding high-profile IBD experts to its Clinical Advisory Board (Jan 16, Jan 29 2026) and highlighting data and visibility via major conferences and posters (Crohn’s & Colitis Congress, ECCO 2026, Oppenheimer and Piper Sandler events). Despite these generally constructive updates, four of the last five news items saw negative 24‑hour price reactions, so today’s positive Phase 1b translational data arrives against a backdrop of prior sell-the-news behavior.

Regulatory & Risk Context

Active S-3 Shelf

Shelf Active

Active S-3 Shelf Registration 2025-08-15

An effective shelf registration on Form S-3 was filed on August 15, 2025, listing 988,872 shares and disclosing estimated offering expenses including $20,000 in legal fees, $17,500 in accountants’ fees and total expenses of $49,000. The shelf has seen at least one related 424B4 usage filing on 2025-10-02.

Market Pulse Summary

This announcement highlights Phase 1b translational findings for PALI-2108, showing localized colon ...

Analysis

This announcement highlights Phase 1b translational findings for PALI-2108, showing localized colon activity with 100% clinical response and 40% remission after 7 days, supported by improvements in histology and biomarkers across 89 subjects. Recent history shows multiple positive updates but mixed price reactions. Investors may watch for larger, longer studies, regulatory milestones, and any future use of the existing S-3 registration as key markers of program and balance sheet risk.

Key Terms

ulcerative colitis, pde4 inhibitor prodrugs, rna sequencing, nf-κb, +3 more

7 terms

ulcerative colitis medical

"improvement in Ulcerative Colitis: Phase 1b Translational Findings,” highlights data"

A long-term inflammatory disease that causes repeated sores and irritation in the large intestine, leading to symptoms such as abdominal pain, urgent diarrhea, and fatigue. For investors, it matters because the condition creates a steady need for effective treatments, influences the size of drug and medical-device markets, and makes clinical trial results, regulatory decisions and treatment approvals material to companies’ revenue prospects—like watching for fixes to a recurring leak in an important building system.

pde4 inhibitor prodrugs medical

"oral PDE4 inhibitor prodrugs designed for targeted delivery to the terminal ileum"

PDE4 inhibitor prodrugs are inactive chemical versions of drugs designed to become active inhibitors of the PDE4 enzyme once processed in the body; PDE4 controls cellular signals linked to inflammation and other conditions. Think of a prodrug as a sealed package that opens inside the body to release the real medicine. Investors care because prodrugs can improve how well a drug works, reduce side effects, extend patent life or simplify dosing, all of which affect clinical success, regulatory approval and commercial value.

rna sequencing medical

"Colon biopsy RNA sequencing revealed: Significant downregulation of inflammatory"

RNA sequencing is a laboratory method that reads the active genetic messages inside cells, like scanning the recipe cards a cell is using at a given moment to make proteins. For investors, it matters because the results can reveal how diseases operate, identify targets for new drugs or diagnostics, and help companies show whether a treatment is working—information that can change a biotech firm's value much like a new product test result can affect a tech stock.

nf-κb medical

"Suppression of TNF-α, JAK–STAT, NF-κB, MAPK and TGF-β pathway activity"

NF-κB is a protein complex inside cells that acts like a master switch for inflammation, immune responses and cell survival; when turned on it tells many genes to produce signals that promote immune activity, cell growth or protection from stress. Investors care because drugs or diagnostics that affect NF-κB can influence treatments for cancers, autoimmune disorders and inflammatory diseases, so changes in NF-κB activity can meaningfully alter a therapy’s potential market and risk profile.

mapk medical

"Suppression of TNF-α, JAK–STAT, NF-κB, MAPK and TGF-β pathway activity"

MAPK (Mitogen‑Activated Protein Kinase) is a family of enzymes in cells that act like switches or traffic signals, passing along messages that tell cells to grow, divide, or respond to stress. It matters to investors because abnormal MAPK signaling is implicated in cancers and other diseases, making these enzymes common targets for drugs and diagnostics; progress or setbacks in MAPK‑related research can materially affect the value of biotech and pharmaceutical companies.

tgf-β medical

"Suppression of TNF-α, JAK–STAT, NF-κB, MAPK and TGF-β pathway activity"

TGF-β (transforming growth factor beta) is a naturally occurring signaling protein that cells use to control growth, repair and immune responses; think of it as a traffic light that can either slow, stop or redirect cellular behavior depending on the situation. It matters to investors because drugs that block or boost TGF-β pathways are key candidates for treating cancer, fibrosis and autoimmune conditions, and trial outcomes or regulatory news about these therapies can greatly affect a biotech company’s value.

fecal calprotectin medical

"Histologic improvement and reductions in fecal calprotectin and hsCRP were observed"

A fecal calprotectin test measures the level of a specific protein shed into stool when the intestines are inflamed; higher levels signal active inflammation in the gut. Investors watch this marker because it is used in clinical trials, diagnostic labs, and treatment decisions to show whether therapies for inflammatory bowel diseases are working or if patients need further care, making it a practical indicator of market demand for diagnostics and drugs.

AI-generated analysis. Not financial advice.

Phase 1b translational data demonstrate localized ileocolonic target engagement, suppression of inflammatory and fibrotic gene programs, and early clinical response within seven days

Encouraging safety profile across 89 subjects supports differentiated, colon-targeted PDE4 approach

Translational analyses confirm local suppression of TNF-α, JAK–STAT, NF-κB, MAPK and TGF-β signaling in colon tissue with minimal peripheral immune modulation

Data presented at the 21st Congress of the European Crohn’s and Colitis Organization (ECCO) in Stockholm, Sweden

Carlsbad, CA, Feb. 23, 2026 (GLOBE NEWSWIRE) -- Palisade Bio, Inc. (Nasdaq: PALI) (“Palisade” or the “Company”), a clinical-stage biopharmaceutical company developing next-generation, once-daily, oral PDE4 inhibitor prodrugs designed for targeted delivery to the terminal ileum and colon, today announced the presentation of new translational data for PALI-2108 at the 21st Congress of the European Crohn’s and Colitis Organization (ECCO) in Stockholm, Sweden.

The poster, titled “Oral Locally Bioactivated PDE4 Inhibitor Prodrug PALI-2108 Demonstrates Rapid Clinical, Histologic, and Biomarker Improvement in Ulcerative Colitis: Phase 1b Translational Findings,” highlights data showing that PALI-2108 produced measurable clinical response within seven days, improved histologic markers of inflammation in colon tissue, and reduced key inflammatory biomarkers. The data also demonstrates localized pharmacologic activity in the colon, including reduced PDE4B expression and modulation of inflammatory signaling pathways, supporting the intended targeted mechanism of the program. Access the poster here.

Key Highlights

Colon biopsy RNA sequencing revealed:

• Significant downregulation of inflammatory and fibrosis-associated gene expression programs
• Suppression of TNF-α, JAK–STAT, NF-κB, MAPK and TGF-β pathway activity using PROGENy-derived pathway scoring
• Reduced inflammatory cell signatures, including lymphocyte-associated markers, based on cellular deconvolution analyses
• Decreased mucosal PDE4B expression accompanied by increased tissue cAMP levels
  
  

Clinical Context:

As previously reported, in the Phase 1b cohort of patients with moderate-to-severe ulcerative colitis (UC) treated for seven days:

• 100% achieved clinical response by modified Mayo Score
• 40% achieved clinical remission by modified Mayo Score
• Histologic improvement and reductions in fecal calprotectin and hsCRP were observed
• Demonstrated localized target engagement in colon tissue with reduced PDE4B expression and increased cAMP
• No UC patient discontinuations (which follows the Company’s earlier findings of no serious adverse events across 84 normal healthy volunteers)
  
  

“These mechanistic data provide important molecular support for PALI-2108’s colon-targeted design,” said Mitch Jones, M.D., Ph.D., President and Chief Medical Officer of Palisade Bio. “RNA sequencing and pathway analyses demonstrate suppression of key inflammatory and fibrotic signaling networks directly within colonic tissue, while peripheral immune profiles remain largely unchanged. This localized pharmacology supports our strategy to enhance the therapeutic index of PDE4 inhibition by concentrating activity at the site of disease.”

In the Phase 1b cohort, five adults with moderate-to-severe UC received titrated PALI-2108 for seven days. All patients achieved clinical response, with a subset reaching clinical remission. Improvements were accompanied by reductions in mucosal inflammatory gene expression, fibrosis-associated gene signatures and key inflammatory pathways including JAK-STAT, NF-κB, TNF-α, MAPK, and TGF-β. Colon tissue analyses demonstrated reduced lymphocyte infiltration, decreased neutrophil signatures and broad dampening of inflammatory programs consistent with PDE4 inhibition–mediated elevation of cAMP. Importantly, peripheral blood immune profiles remained largely unchanged, supporting localized pharmacologic activity in the colon.

Dr. Jones added, “We believe the convergence of pharmacokinetics, tissue pharmacodynamics, gene expression modulation and previously reported clinical responses helps to further de-risk the program as we advance PALI-2108 into later-stage development.”

About PALI-2108

PALI-2108 is a once-daily, oral prodrug designed for targeted delivery of PDE4 inhibition to the terminal ileum and colon through local bacterial bioactivation. The prodrug is pharmacologically inactive until it reaches the lower intestine, where bacterial enzymes convert it into the active PDE4 inhibitor at sites of inflammation and fibrosis. This targeted activation strategy prevents absorption in the upper gut, enables sustained local exposure with controlled systemic distribution, and is engineered to reduce peak plasma levels, thereby improving the overall therapeutic index and reducing tolerability limitations such as diarrhea, nausea and headache that have constrained systemic PDE4 inhibitors.

About Palisade Bio

Palisade Bio, Inc. (Nasdaq: PALI) (“Palisade” or the “Company”) is a clinical-stage biopharmaceutical company advancing a next generation oral PDE4 inhibitor prodrugs designed to improve pharmacology, tolerability and convenience for patients with inflammatory and fibrotic diseases. Through its differentiated prodrug platform and precision pharmacology strategy, Palisade Bio is committed to transforming proven PDE4 biology into better, safer oral therapies for patients living with chronic inflammatory and fibrotic diseases.

The Company’s lead program, PALI-2108, is a once-daily oral PDE4 inhibitor prodrug designed to be selectively bioactivated in the ileum and colon, initiating targeted PDE4 inhibition at sites of disease while enabling systemic distribution of the active drug. In a recently reported Phase 1b trial, PALI-2108 achieved a 100% clinical response in the UC cohort, with no serious adverse events, favorable tolerability and pharmacokinetics consistent with localized activation in the lower intestine, low systemic exposure, and controlled release within the GI tract.

Palisade Bio is now advancing towards a Phase 2 clinical study in UC designed to evaluate clinical remission, response and pharmacodynamic biomarkers over 12 weeks, with an extension phase assessing maintenance of remission. In addition, the Company is completing early studies in fibrostenotic crohn’s disease to further characterize PALI-2108’s safety, pharmacology and potential therapeutic benefit across inflammatory bowel disease indications. 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 timing and results of clinical trials, the potential mechanisms of action and therapeutic benefits of PALI-2108, and plans for regulatory submissions. 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, 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; 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 clinical results did PALI report for PALI-2108 in the Phase 1b UC cohort (PALI)?

All five Phase 1b patients achieved clinical response within seven days, with 40% reaching clinical remission. According to the company, histologic improvement, reductions in fecal calprotectin and hsCRP, and no UC discontinuations were also observed.

How did PALI-2108 affect colon tissue biomarkers and signaling pathways (PALI)?

PALI-2108 reduced mucosal PDE4B expression and increased tissue cAMP, indicating local pharmacology. According to the company, RNA sequencing showed downregulation of TNF‑α, JAK–STAT, NF‑κB, MAPK and TGF‑β pathway activity in colon biopsies.

What safety information did Palisade provide for PALI-2108 across study subjects (PALI)?

The company reported an encouraging safety profile with no UC patient discontinuations in Phase 1b and prior no serious adverse events across 84 healthy volunteers. According to the company, overall safety supports the colon‑targeted approach.

Does PALI-2108 show peripheral immune modulation or remain localized to the colon (PALI)?

Peripheral blood immune profiles remained largely unchanged, suggesting localized colon activity rather than systemic immune suppression. According to the company, translational analyses support minimal peripheral immune modulation alongside local effects.

How robust are the Phase 1b translational findings for PALI-2108 (PALI)?

Findings are promising but limited by small sample size and short treatment duration. According to the company, molecular and clinical convergence de‑rises risk but larger, longer trials are needed for confirmation.

Where and when were PALI-2108 translational data presented (PALI)?

Data were presented at the 21st Congress of the European Crohn’s and Colitis Organization (ECCO) in Stockholm, Sweden. According to the company, the poster summarized Phase 1b RNA sequencing and biomarker results supporting colon‑targeted activity.