Palisade Bio Reports Additional Phase 1a/b Data Demonstrating Colon-Targeted Exposure and Sustained IC90 Coverage Supporting Once-Daily Dosing in Ulcerative Colitis

Rhea-AI Summary

Palisade Bio (NASDAQ: PALI) reported additional Phase 1a/b analyses of PALI-2108 showing colon-targeted activation, ~6-fold tissue-to-plasma exposure, and steady-state active metabolite (PALI-0008) troughs above IC90 supporting once-daily dosing. Biomarkers and histology improved: fecal calprotectin ~70% lower; Nancy, Robarts, and Geboes scores declined.

Findings presented at Digestive Disease Week 2026 support localized pharmacology and continued clinical development in ulcerative colitis.

Positive

• PALI-0008 troughs exceeded IC90 at steady state, supporting continuous target engagement
• Tissue-to-plasma ratio ~6-fold, indicating preferential intestinal localization
• Fecal calprotectin reduced by ~70%, a key inflammatory biomarker
• Histology improvements: Nancy −58%, Robarts −56%, Geboes −36%
• Clinical outcomes: 100% clinical response and 40% clinical remission reported

Negative

• None.

Key Figures

PALI-0008 trough vs Cmax: ≈20% higher than single-dose Cmax Time to steady state: ~48 hours Tissue-to-plasma ratio: ≈6-fold +5 more

8 metrics

PALI-0008 trough vs Cmax ≈20% higher than single-dose Cmax Steady-state pre-dose trough vs single-dose Cmax

Time to steady state ~48 hours Active metabolite PALI-0008 steady-state achievement

Tissue-to-plasma ratio ≈6-fold Colon tissue-to-plasma exposure for active metabolite

PDE4B reduction ~71% decrease Mucosal PDE4B expression change

cAMP increase ~27% increase Mucosal cAMP biomarker change

Lymphocyte reduction ~30–40% decrease Lymphocyte count change with treatment

Fecal calprotectin ~70% decrease Inflammatory biomarker reduction

Clinical response/remission 100% response, 40% remission Previously reported Phase 1a/b outcomes

Market Reality Check

Price: $2.13 Vol: Volume 2,900,239 is below...

low vol

$2.13 Last Close

Volume Volume 2,900,239 is below the 20-day average of 4,357,290 (relative volume 0.67). low

Technical Shares at $2.13 are trading above the 200-day MA at $1.62 and about 25% below the 52-week high of $2.855.

Peers on Argus

PALI shows a 7.04% gain while key peers are mixed (e.g., GRI up 3.67%, ADTX down...

1 Down

PALI shows a 7.04% gain while key peers are mixed (e.g., GRI up 3.67%, ADTX down 11.36%, TTNP down 3.96%). Momentum scanners only flag ONCO moving down, reinforcing that PALI’s move appears stock-specific rather than a broad biotech rotation.

Historical Context

5 past events · Latest: Apr 16 (Positive)

Pattern 5 events

Date	Event	Sentiment	Move	Catalyst
Apr 16	Conference poster update	Positive	-0.4%	Announcement of DDW 2026 poster on PALI-2108 Phase 1 translational data.
Apr 08	Investor conference	Neutral	-2.1%	Needham healthcare conference presentation and investor meetings scheduling.
Mar 30	Clinical topline data	Positive	-1.7%	Positive Phase 1b topline data in fibrostenotic Crohn’s disease for PALI-2108.
Mar 02	Investor conferences	Neutral	+2.3%	Participation in TD Cowen and Leerink healthcare investor conferences.
Feb 23	Clinical data update	Positive	+0.6%	ECCO 2026 Phase 1b data showing rapid colon‑targeted activity of PALI-2108.

Pattern Detected

Recent positive clinical and data-presentation headlines often saw flat to negative next-day moves, suggesting a tendency for muted or contrary reactions to favorable news.

Recent Company History

Over the last six months, Palisade Bio has repeatedly highlighted progress for PALI-2108, including Phase 1b translational data at ECCO 2026 and positive topline results in fibrostenotic Crohn’s disease showing a 47.5% SES-CD reduction. The company also announced multiple conference and investor presentations plus today’s detailed Phase 1a/b PK and mechanistic findings in ulcerative colitis. Despite generally favorable data, prior market reactions were modest, with some positive updates followed by small share price declines.

Regulatory & Risk Context

Active S-3 Shelf · $49,000

Shelf Active

Active S-3 Shelf Registration 2025-08-15

$49,000 registered capacity

Palisade Bio has an active S-3 shelf filed on August 15, 2025, covering 988,872 shares, noted as 10.24% of the referenced share count. The filing discloses estimated offering expenses totaling $49,000, including legal and accounting fees, and has seen at least one usage via a 424B4 supplement in October 2025.

Market Pulse Summary

This announcement details additional Phase 1a/b pharmacokinetic and translational findings for PALI-...

Analysis

This announcement details additional Phase 1a/b pharmacokinetic and translational findings for PALI-2108, showing colon-targeted exposure, tissue-to-plasma ratios around 6-fold, and strong biomarker shifts such as ~71% PDE4B reduction and ~70% fecal calprotectin decline. These build on prior data with 100% clinical response and 40% remission. Investors may track upcoming Phase 2 trial progress, regulatory updates, and any further financing steps alongside this mechanistic validation.

Key Terms

pde4, camp, pharmacokinetic, half-life, +3 more

7 terms

pde4 medical

"once-daily, oral PDE4 inhibitor prodrugs designed for targeted delivery"

PDE4 is an enzyme in the body that helps turn down certain cellular signals involved in inflammation and brain activity; think of it as a volume knob that lowers a chemical signal. Drugs that block PDE4 can boost those signals to reduce inflammation or alter mood, so progress or setbacks in developing PDE4-targeting drugs can materially affect a biotech or pharmaceutical company's clinical trial outcomes, regulatory prospects, and potential future revenue.

camp medical

"PDE4/cAMP pathway modulation and sustained active metabolite exposure"

A "camp" is a group of people or stakeholders who share the same viewpoint, strategy or stance on a corporate issue—for example investors, board members, managers or activist campaigns. Knowing which camp is gaining influence matters to investors because it signals likely decisions, voting outcomes or strategic shifts that can change a company’s direction and therefore its value; think of it like teams in a debate whose winning argument steers the outcome.

pharmacokinetic medical

"steady-state pharmacokinetic findings provide mechanistic support"

Pharmacokinetic describes how a drug moves through and leaves the body — how it is absorbed, spread to tissues, broken down and excreted — like tracking a package from pickup to delivery and disposal. For investors, these properties determine effective dose, safety risks, how often a medicine must be taken, and how reliably it works, which in turn influence clinical trial success, regulatory approval chances, production complexity and a drug’s commercial value.

half-life medical

"The active metabolite exhibited an extended half-life and reached steady state"

Half-life is the time it takes for a quantity (such as a drug in the body, a radioactive substance, or a decaying revenue stream) to decrease to half its original amount. Think of it like the time it takes for a hot cup of coffee to cool to half its initial warmth: it tells you how quickly the effect fades. For investors, half-life helps estimate how long a product’s impact, a payment stream, or a risk factor will meaningfully influence a company’s performance.

jak–stat medical

"suppression of key inflammatory and fibrotic pathways, including JAK–STAT, NF-κB, TNF-α"

A cell communication route that carries messages from molecules outside a cell into its nucleus so the cell can change behavior, using proteins called JAKs and STATs like a two-person relay team passing instructions. It matters to investors because many medicines for autoimmune diseases, cancers and inflammatory conditions aim to block or tweak this pathway; drug trial results, regulatory approvals or safety concerns tied to JAK–STAT modulation can strongly affect a biotech or pharmaceutical company's value.

nf-κb medical

"suppression of key inflammatory and fibrotic pathways, including JAK–STAT, NF-κB, TNF-α"

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.

fecal calprotectin medical

"decreases in fecal calprotectin (~70%). Further, histological improvements"

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.

Data demonstrate colon tissue PDE4/cAMP pathway modulation and sustained active metabolite exposure above IC90 across the dosing interval

Steady-state pharmacokinetic findings provide mechanistic support for previously reported Phase 1b clinical activity

Additional findings support PALI-2108’s potential as a once-daily, gut-targeted oral therapy

Data presented at Digestive Disease Week 2026 – Access the Poster Here

Denver, CO, May 05, 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 additional Phase 1a/b analyses of PALI-2108, including delayed ileocolonic activation, high tissue-to-plasma exposure, and sustained steady-state concentrations of the active metabolite (PALI-0008) above IC90, at Digestive Disease Week 2026, further characterizing the pharmacokinetic and translational profile of the program.

These findings build on previously reported positive data demonstrating rapid improvements across clinical, histologic, and biomarker endpoints in ulcerative colitis. Additional analyses describe a differentiated pharmacokinetic profile, including steady-state trough concentrations of PALI-0008 relative to IC90 that are consistent with sustained target engagement over the dosing interval.

Additional pharmacokinetic and translational findings show a steady-state pharmacokinetic analyses demonstrated that pre-dose trough concentrations of the active metabolite PALI-0008 exceeded the IC90 threshold and were approximately 20% higher than single-dose Cmax, supporting continuous target inhibition across the dosing interval. The active metabolite exhibited an extended half-life and reached steady state within ~48 hours, supporting once-daily dosing. Tissue-to-plasma exposure ratios of approximately 6-fold further support preferential localization of drug activity to the intestinal mucosa. Treatment with PALI-2108 resulted in colon-selective suppression of key inflammatory and fibrotic pathways, including JAK–STAT, NF-κB, TNF-α, and TGF-β signaling. These transcriptional changes were observed in colonic tissue but not peripheral blood, supporting localized pharmacologic activity. These effects were supported by biomarker changes consistent with PDE4 inhibition, including decreased mucosal PDE4B expression (~71%), increased cAMP (~27%), reductions in lymphocytes (~30–40%), and decreases in fecal calprotectin (~70%). Further, histological improvements were observed across multiple indices, including reductions in Nancy score (−58%), Robarts Histopathology Index (−56%), and Geboes score (−36%).

“These additional pharmacokinetic and translational analyses further characterize the differentiated profile of PALI-2108, which is designed to be selectively bioactivated in the ileum and colon,” said Mitch Jones, President and Chief Medical Officer of Palisade Bio. “We are encouraged by the sustained steady-state trough levels of the active metabolite, PALI-0008, relative to the IC90 threshold, with trough levels exceeding IC90 throughout the dosing interval, a profile that compares favorably to currently approved systemic PDE4 inhibitors. The observed colon-selective pathway modulation further supports our strategy of localized bioactivation to maximize efficacy while minimizing systemic exposure. We believe this differentiated profile strengthens the case for PALI-2108 as a once-daily oral therapy in ulcerative colitis.”

Previously reported Phase 1a/b data demonstrated rapid and consistent improvements across clinical, histologic, and biomarker endpoints. PALI-2108 showed robust pharmacodynamic activity, including increased cAMP and decreased PDE4B expression, along with reductions in inflammatory markers such as fecal calprotectin, hsCRP and lymphocyte counts. These findings were associated with clinical outcomes, with 100% of patients achieving clinical response and 40% achieving clinical remission. Collectively, these findings highlight a differentiated profile characterized by localized drug activation, sustained target inhibition above IC90, and colon-selective pharmacodynamic effects, supporting continued clinical development of PALI-2108 as a next-generation PDE4 inhibitor for inflammatory bowel disease.

The poster titled, “Gut-Targeted PDE4 Inhibition with PALI-2108 Demonstrates Rapid Clinical, Histologic, and Biomarker Improvement in Ulcerative Colitis: Translational Findings from a Phase 1 Study,” can be accessed here.

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 prodrug 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. PALI-2108 has demonstrated positive results in a Phase 1a and two Phase 1b clinical trials, including studies in ulcerative colitis (UC) and fibrostenotic Crohn’s Disease (FSCD).

Palisade Bio is now advancing towards two Phase 2 clinical studies in UC and Crohn’s disease (CD). 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: the potential mechanisms of action and therapeutic benefits of PALI-2108, dosing levels and timing 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 and efficacy, dosing or durability of effect, observed from preclinical or clinical trials with a limited number of patients, 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, 2025, filed with the Securities and Exchange Commission (“SEC”) on March 20, 2026, 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 did Palisade Bio announce about PALI-2108 pharmacokinetics (PALI) on May 5, 2026?

Palisade reported steady-state PALI-0008 trough levels above the IC90 threshold, supporting once-daily dosing. According to the company, troughs exceeded IC90 and reached steady state within ~48 hours, with trough concentrations about 20% higher than single-dose Cmax.

How does PALI-2108 localize to the colon and why does that matter for PALI investors?

Palisade described delayed ileocolonic activation and ~6-fold tissue-to-plasma exposure, indicating colon-targeted delivery. According to the company, this preferential localization produced colonic pharmacodynamic effects while limiting peripheral blood changes, supporting localized activity for ulcerative colitis.

What biomarker and histologic changes did Palisade report for PALI-2108 in UC patients?

The company reported mucosal PDE4B down ~71%, cAMP up ~27%, lymphocytes down ~30–40%, and fecal calprotectin down ~70%. According to the company, histologic indices fell: Nancy −58%, Robarts −56%, Geboes −36%.

Does the May 5, 2026 data support once-daily dosing for PALI-2108 (PALI)?

Yes. The company reported an extended active-metabolite half-life and steady state within ~48 hours, supporting once-daily administration. According to the company, pre-dose troughs remained above IC90 throughout the dosing interval.

What clinical outcomes were observed with PALI-2108 in the Phase 1a/b study (PALI)?

Palisade reported 100% of patients achieved clinical response and 40% achieved clinical remission in the Phase 1a/b dataset. According to the company, these clinical outcomes aligned with biomarker and histologic improvements reported.