Palisade Bio to Present Preclinical Results for PALI-2108 Demonstrating Engagement of Key Fibrotic Pathways of Crohn's Disease and Ulcerative Colitis (UC)
Palisade Bio announced preclinical results for PALI-2108, a novel local PDE4 inhibitor prodrug, showing promising effects in treating fibrostenotic Crohn's disease. Studies using the DSS colitis mouse model demonstrated that PALI-2108 modulated 187 genes involved in four main fibrotic pathways of IBD, with dose-dependent effects. The drug is designed for local activation in the ileum and colon, potentially offering enhanced safety compared to traditional systemic PDE4 inhibitors. The company is currently conducting a Phase 1 study with topline data expected in first half of 2025.
Palisade Bio ha annunciato i risultati preclinici per PALI-2108, un nuovo pro-farmaco inibitore locale della PDE4, che mostra effetti promettenti nel trattamento della malattia di Crohn fibrostenotica. Gli studi condotti utilizzando il modello murino di colite indotta da DSS hanno dimostrato che PALI-2108 ha modulato 187 geni coinvolti in quattro principali vie fibrotiche della IBD, con effetti dose-dipendenti. Il farmaco è progettato per un'attivazione locale nell'ileo e nel colon, potenzialmente offrendo una maggiore sicurezza rispetto agli inibitori sistemici della PDE4 tradizionali. Attualmente, l'azienda sta conducendo uno studio di Fase 1 con i dati principali attesi nella prima metà del 2025.
Palisade Bio anunció resultados preclínicos para PALI-2108, un nuevo profármaco inhibidor local de PDE4, que muestra efectos prometedores en el tratamiento de la enfermedad de Crohn fibrostenótica. Los estudios realizados utilizando el modelo de ratón de colitis inducida por DSS demostraron que PALI-2108 moduló 187 genes involucrados en cuatro vías fibróticas principales de la EII, con efectos dependientes de la dosis. El fármaco está diseñado para activarse localmente en el íleon y el colon, ofreciendo potencialmente una mayor seguridad en comparación con los inhibidores sistémicos tradicionales de PDE4. La empresa está llevando a cabo actualmente un estudio de Fase 1, con los datos principales esperados para la primera mitad de 2025.
Palisade Bio는 PALI-2108, 새로운 국소 PDE4 억제제 프로드럭의 전임상 결과를 발표했으며, 이는 섬유 좁아짐 크론병 치료에 유망한 효과를 보여줍니다. DSS 콜리티스 마우스 모델을 사용한 연구에서 PALI-2108이 IBD의 네 가지 주요 섬유증 경로와 관련된 187개의 유전자를 조절한다는 것이 입증되었으며, 용량 의존적인 효과를 보였습니다. 이 약물은 회장과 대장 내에서 국소적으로 활성화되도록 설계되었으며, 전통적인 전신 PDE4 억제제에 비해 향상된 안전성을 제공할 수 있습니다. 현재 회사는 2025년 상반기에 주요 데이터가 예상되는 1상 연구를 진행하고 있습니다.
Palisade Bio a annoncé des résultats précliniques pour PALI-2108, un nouveau pro-médicament inhibiteur local de la PDE4, montrant des effets prometteurs dans le traitement de la maladie de Crohn fibrostenotique. Des études utilisant le modèle murin de colite induite par DSS ont démontré que PALI-2108 modulait 187 gènes impliqués dans quatre principales voies fibrosiques de la MII, avec des effets dépendants de la dose. Le médicament est conçu pour une activation locale dans l'iléon et le côlon, offrant potentiellement une sécurité accrue par rapport aux inhibiteurs systémiques de la PDE4 traditionnels. L'entreprise mène actuellement une étude de Phase 1, avec des données principales attendues dans la première moitié de 2025.
Palisade Bio hat präklinische Ergebnisse für PALI-2108 bekannt gegeben, ein neuartiges lokales PDE4-Inhibitor-Prodrug, das vielversprechende Effekte bei der Behandlung der fibrostenotischen Morbus Crohn zeigt. Studien mit dem DSS-Kolitis-Mausmodell haben gezeigt, dass PALI-2108 187 Gene moduliert, die in vier Hauptfaserwege der IBD involviert sind, mit dosisabhängigen Effekten. Das Medikament ist für die lokale Aktivierung im Ileum und im Colon konzipiert und könnte potenziell eine verbesserte Sicherheit im Vergleich zu herkömmlichen systemischen PDE4-Inhibitoren bieten. Das Unternehmen führt derzeit eine Phase-1-Studie durch, deren wichtigste Daten in der ersten Hälfte von 2025 erwartet werden.
- Preclinical data shows PALI-2108 effectively modulates 187 genes in key fibrotic pathways
- Drug demonstrates dose-dependent positive effects in IBD animal model
- Local activation mechanism may reduce systemic side effects compared to existing treatments
- Phase 1 clinical trial is already ongoing with results expected H1 2025
- Drug is still in early development stages (preclinical/Phase 1)
- Efficacy in human subjects yet to be demonstrated
- Competition from established treatments like roflumilast and apremilast
Insights
The preclinical results for PALI-2108 demonstrate significant potential in treating fibrostenotic Crohn's disease. The drug's ability to modulate 187 genes across four main fibrotic pathways represents a comprehensive approach to addressing both inflammation and fibrosis. Key differentiators include:
- Local activation in the ileum and colon, potentially reducing systemic side effects
- Dose-dependent enhancement of the fibrotic signature
- Dual anti-inflammatory and anti-fibrotic mechanisms
- Reduction in PDE4B expression while increasing cAMP levels
However, investors should note that while preclinical data is promising, the ongoing Phase 1 trial with results expected in H1 2025 will be important in validating these findings in humans. The market opportunity is substantial, as approximately
Data to be presented at the 8th Annual Antifibrotic Drug Development (AFDD) Summit
PALI-2108 may offer a solution for fibrostenotic Crohn’s disease by enhancing efficacy, safety, and therapeutic potential compared to traditional treatments
Carlsbad, CA, Nov. 21, 2024 (GLOBE NEWSWIRE) -- Palisade Bio, a clinical-stage biopharmaceutical company focused on developing novel therapeutics for autoimmune, inflammatory, and fibrotic diseases, today announced preclinical results for PALI-2108, a novel local PDE4 inhibitor prodrug. In recent studies using the Dextran Sulfate Sodium (DSS) colitis mouse model, PALI-2108 demonstrated a dose-dependent effect on key fibrotic pathways, underscoring its potential as an effective treatment for fibrostenotic Crohn’s disease.
The data will be presented as part of an invited talk titled, "Detailing Characteristics of Fibrostenotic Crohn’s Disease Biology & the Potential of a Local PDE4 Inhibitor Prodrug to Minimize Off-Target Effects & Maximize Efficacy," delivered by Mitch Jones, MD, PhD, Chief Medical Officer of Palisade Bio, at the 8th Annual Antifibrotic Drug Development Summit, being held November 19-21, 2024, in Boston, MA.
“There remains an unmet need in Crohn’s disease, with a number of patients experiencing substantial fibrosis resulting in stenosis at least once in their lifetime, often necessitating surgical intervention,” said Dr. Jones. “Our findings in the DSS mouse model seem to demonstrate that PALI-2108 holds considerable promise as a targeted, dual-action (pleiotropic) anti-inflammatory and anti-fibrotic agent for treating fibrostenotic Crohn’s disease, a condition we believe is inadequately addressed by current therapies. The data seems to indicate that PALI-2108 engages and modulates key fibrotic pathways directly in the intestinal and colonic mucosa, addressing the root cause of fibrosis while minimizing systemic side effects commonly associated with systemic PDE4 inhibitors. This offers what we believe could be a safer and more effective treatment option for patients.”
The study evaluated PALI-2108 in an animal model of inflammatory bowel disease (IBD), often complicated by intestinal fibrosis. PALI-2108, a prodrug activated locally in the ileum and colon, was found to modulate key fibrotic pathways associated with both Crohn’s disease and UC. A comprehensive analysis of gene expression revealed that PALI-2108 affected 187 genes involved in the four main fibrotic pathways of IBD, demonstrating an upregulation and downregulation of key markers. This suggests that PALI-2108 has the potential to reverse or prevent fibrotic progression in the intestines.
The study further revealed that PALI-2108 reduced key intracellular markers of inflammation and fibrosis in the colon, including PDE4B expression, while increasing cAMP levels—a crucial factor in maintaining tissue homeostasis. Notably, the dose-response relationship showed that higher doses of PALI-2108 further enhanced the fibrotic signature, reinforcing its potential as an effective, localized treatment for patients suffering from fibrostenotic Crohn’s disease. The data also seemed to demonstrate that PALI-2108 offers enhanced safety and therapeutic potential compared to traditional treatments. Unlike systemic PDE4 inhibitors, PALI-2108 is designed to be activated locally, reducing the risk of common side effects such as nausea, which are frequently seen with oral PDE4 inhibitors like oral and inhaled roflumilast (AstraZeneca) for fibrotic COPD and oral apremilast (Amgen) and for inflammatory diseases like psoriasis and psoriatic arthritis.
The Company is evaluating PALI-2108 in a Phase 1 single-center, double-blind, placebo-controlled study focused on safety, tolerability, pharmacokinetics, and pharmacodynamics in healthy volunteers, alongside an open-label study involving UC patients. Topline data from the Phase 1 study is expected in the first half of 2025. For more information, visit clinicaltrials.gov and reference identifier NCT06663605.
About PALI-2108
PALI-2108 is an orally administered, locally acting colon-specific PDE4 inhibitor prodrug in development for patients affected by UC. The Company recently commenced a Phase 1 single-center, double-blind, placebo-controlled study of PALI-2108 focused on safety, tolerability, pharmacokinetics, and pharmacodynamics in healthy volunteers, alongside an open-label study involving a patient cohort with UC. It is anticipated that the comprehensive data gathered will support Palisade Bio’s precision medicine strategy, aimed at identifying patient responders for future clinical studies.
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
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Investor Relations Contact
JTC Team, LLC
Jenene Thomas
908-824-0775
PALI@jtcir.com
FAQ
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