Palisade Bio Reports 100% Clinical Response in Phase 1b Ulcerative Colitis Cohort with Novel PDE4 Inhibitor, PALI-2108
Palisade Bio (NASDAQ:PALI) announced breakthrough results from its Phase 1b clinical trial of PALI-2108, a first-in-class PDE4 inhibitor for ulcerative colitis treatment. The study achieved a remarkable 100% clinical response rate in all five patients with moderate-to-severe UC, demonstrating a mean 62.8% reduction in modified Mayo score.
The drug showed strong safety profile with no serious adverse events, and tissue analyses confirmed significant therapeutic effects including 40% decrease in tissue lymphocytes and 51% reduction in PDE4B expression. Phase 1a multiple ascending dose cohort data supported convenient once-daily dosing, with the active metabolite remaining detectable in colon tissue for over 36 hours.
Palisade Bio plans to complete a Phase 1b study in fibrostenotic Crohn's disease by H2 2025 and submit a Phase 2 IND application to FDA in H1 2026.
Palisade Bio (NASDAQ:PALI) ha annunciato risultati rivoluzionari dal suo trial clinico di Fase 1b su PALI-2108, un inibitore PDE4 di prima classe per il trattamento della colite ulcerosa. Lo studio ha raggiunto un eccezionale 100% di risposta clinica in tutti e cinque i pazienti con colite ulcerosa da moderata a grave, mostrando una riduzione media del 62,8% nel punteggio Mayo modificato.
Il farmaco ha evidenziato un profilo di sicurezza solido senza eventi avversi gravi, e le analisi tissutali hanno confermato effetti terapeutici significativi, tra cui una riduzione del 40% dei linfociti nel tessuto e una diminuzione del 51% dell'espressione di PDE4B. I dati della coorte a dosi ascendenti multiple di Fase 1a hanno supportato una comoda somministrazione una volta al giorno, con il metabolita attivo rilevabile nel tessuto del colon per oltre 36 ore.
Palisade Bio prevede di completare uno studio di Fase 1b sulla malattia di Crohn fibrostenotica entro la seconda met脿 del 2025 e di presentare una domanda IND per la Fase 2 alla FDA nella prima met脿 del 2026.
Palisade Bio (NASDAQ:PALI) anunci贸 resultados revolucionarios de su ensayo cl铆nico de Fase 1b con PALI-2108, un inhibidor PDE4 de primera clase para el tratamiento de la colitis ulcerosa. El estudio logr贸 una notable tasa de respuesta cl铆nica del 100% en los cinco pacientes con colitis ulcerosa de moderada a grave, demostrando una reducci贸n media del 62,8% en la puntuaci贸n modificada de Mayo.
El medicamento mostr贸 un perfil de seguridad s贸lido sin eventos adversos graves, y los an谩lisis tisulares confirmaron efectos terap茅uticos significativos, incluyendo una disminuci贸n del 40% en los linfocitos tisulares y una reducci贸n del 51% en la expresi贸n de PDE4B. Los datos de la cohorte de dosis ascendentes m煤ltiples de Fase 1a respaldaron una dosificaci贸n conveniente una vez al d铆a, con el metabolito activo detectable en el tejido del colon por m谩s de 36 horas.
Palisade Bio planea completar un estudio de Fase 1b en la enfermedad de Crohn fibroest茅notica para la segunda mitad de 2025 y presentar una solicitud IND de Fase 2 a la FDA en la primera mitad de 2026.
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Palisade Bio (NASDAQ:PALI) a annonc茅 des r茅sultats r茅volutionnaires issus de son essai clinique de phase 1b avec PALI-2108, un inhibiteur PDE4 de premi猫re classe pour le traitement de la colite ulc茅reuse. L'茅tude a atteint un taux de r茅ponse clinique de 100% chez les cinq patients atteints de colite ulc茅reuse mod茅r茅e 脿 s茅v猫re, montrant une r茅duction moyenne de 62,8% du score Mayo modifi茅.
Le m茅dicament a pr茅sent茅 un profil de s茅curit茅 solide sans 茅v茅nements ind茅sirables graves, et les analyses tissulaires ont confirm茅 des effets th茅rapeutiques significatifs, incluant une baisse de 40% des lymphocytes tissulaires et une r茅duction de 51% de l'expression de PDE4B. Les donn茅es de la cohorte 脿 doses ascendantes multiples de phase 1a ont soutenu une posologie pratique une fois par jour, avec le m茅tabolite actif d茅tectable dans le tissu du c么lon pendant plus de 36 heures.
Palisade Bio pr茅voit de terminer une 茅tude de phase 1b sur la maladie de Crohn fibro-st茅notique d'ici le second semestre 2025 et de soumettre une demande IND de phase 2 脿 la FDA au premier semestre 2026.
Palisade Bio (NASDAQ:PALI) gab bahnbrechende Ergebnisse aus der Phase-1b-Studie zu PALI-2108 bekannt, einem erstklassigen PDE4-Inhibitor zur Behandlung der Colitis ulcerosa. Die Studie erzielte bei allen f眉nf Patienten mit mittelschwerer bis schwerer Colitis ulcerosa eine bemerkenswerte klinische Ansprechrate von 100% und zeigte eine durchschnittliche Reduktion des modifizierten Mayo-Scores um 62,8%.
Das Medikament zeigte ein gutes Sicherheitsprofil ohne schwerwiegende Nebenwirkungen, und Gewebeanalysen best盲tigten signifikante therapeutische Effekte, darunter eine 40%ige Abnahme der Gewebe-Lymphozyten und eine 51%ige Reduktion der PDE4B-Expression. Daten aus der Phase-1a-Kohorte mit mehrfach ansteigender Dosierung unterst眉tzten eine bequeme einmal t盲gliche Einnahme, wobei der aktive Metabolit 眉ber 36 Stunden im Darmgewebe nachweisbar blieb.
Palisade Bio plant, eine Phase-1b-Studie zur fibrostenotischen Morbus Crohn bis zur zweiten H盲lfte 2025 abzuschlie脽en und im ersten Halbjahr 2026 einen Phase-2-IND-Antrag bei der FDA einzureichen.
- None.
- Small patient sample size (only 5 patients) in Phase 1b trial
- Food intake reduced systemic exposure by up to 42%
Insights
PALI-2108 shows perfect response rate in small UC trial with robust mechanistic data supporting once-daily dosing potential.
The Phase 1b results for PALI-2108 in ulcerative colitis represent a significant clinical development. The 100% response rate (5/5 patients) with a 62.8% mean reduction in modified Mayo scores is remarkable, though the small sample size warrants caution. Most impressive is the comprehensive evidence of mechanism: decreased tissue lymphocytes (40% reduction), increased cAMP levels, and 51% reduction in PDE4B expression collectively validate target engagement.
The histologic improvements across multiple validated indices (Nancy, Robarts, Geboes) align with clinical responses, suggesting genuine disease modification rather than symptomatic relief alone. The biomarker data, particularly the 70% reduction in fecal calprotectin, further corroborates therapeutic activity at the tissue level.
What differentiates PALI-2108 from existing PDE4 inhibitors is its ileocolonic-targeted delivery and extended tissue half-life. The Phase 1a data demonstrating colon tissue drug levels above IC90 at 36 hours post-dose supports once-daily dosing鈥攁 significant advantage over twice-daily regimens for chronic conditions.
The safety profile appears favorable with no serious adverse events and predominantly mild, transient side effects typical of PDE4 inhibitors (headache, nausea). The food effect reducing systemic exposure while improving tolerability suggests a straightforward path to optimizing the therapeutic window.
While these results are promising, they come from a short-duration (7-day) open-label study without a control arm. The true efficacy and durability of response will require confirmation in the planned Phase 2 studies.
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鈥檚 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) (鈥淧alisade鈥�, 鈥淧alisade Bio鈥�, or the 鈥淐ompany鈥�), 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.
鈥淭hese results represent a significant milestone for PALI-2108,鈥� said JD Finley, Chief Executive Officer of Palisade Bio. 鈥淭he 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.鈥�
Dr. Mitchell Jones, Chief Medical Officer added, 鈥淲hat is most compelling about the Phase 1b data is the remarkable consistency across all layers of assessment. The clinical response rate of
Phase 1b UC Cohort:
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 (鈮�30% or 鈮�3-point reduction in modified Mayo score with rectal bleeding subscore 鈮�1) - Mean reduction of
62.8% in modified Mayo score (鈭�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%
- Nancy Index:
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 >
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 鈮�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% 鈫� Cmax, ~20% 鈫� 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鈥檚 disease by the second half of 2025. The Company鈥檚 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 and reference identifier .
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鈥攁 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 .
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鈥檚 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鈥檚 planned Phase 2 clinical studies. These forward-looking statements are based on the Company鈥檚 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鈥檚 forward-looking statements include, among others, the timing of enrollment, commencement and completion of the Company鈥檚 clinical trials; the Company鈥檚 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鈥檚 product candidates in clinical trials focused on the same or different indications; the Company鈥檚 ability to secure additional financing to fund future operations and development of its product candidates; and other factors that are described in the 鈥淩isk Factors鈥� and 鈥淢anagement's Discussion and Analysis of Financial Condition and Results of Operations鈥� sections of the Company鈥檚 Annual Report on Form 10-K for the fiscal year ended December 31, 2024, filed with the Securities and Exchange Commission (鈥淪EC鈥�) 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鈥檚 expectations with regard thereto or any change in events, conditions or circumstances on which any such statements are based.
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