Summary of Palisade Bio FY Conference Call Company Overview - **Company**: Palisade Bio (NasdaqCM:PALI) - **History**: Established approximately 16 years ago, with a significant transformation occurring in summer 2023 after a phase 2 study yielded disappointing results. The company pivoted to focus on a PDE4 inhibitor acquired from Giiant Pharma, which was originally developed in Merck labs in Montreal [4][5]. Core Product and Mechanism - **Product**: PALI-2108, a prodrug PDE4 inhibitor designed to mitigate common adverse effects associated with traditional PDE4 inhibitors, such as diarrhea, headache, and nausea [7][9]. - **Mechanism**: The prodrug formulation allows for gut-restricted action, releasing the active ingredient in the distal gut, thus avoiding upper gastrointestinal issues. It has a long half-life and is administered once daily, which is unique among PDE4 inhibitors [10][11][12]. Clinical Development - **Phase 1A and 1B Studies**: Completed with promising results, including a 63% improvement in modified Mayo score in a small open-label study of 5 ulcerative colitis (UC) patients [18]. - **Phase II Plans**: Enrollment for the Phase II UC study is expected to start in Q3 2026, with top-line results anticipated by the end of 2027. The study aims to include 50-70% bio-experienced patients [23][39]. Market Opportunity - **Fibrostenosing Crohn's Disease (FSCD)**: Identified as a significant unmet need, with 75% of Crohn's patients requiring surgery for strictures. There are approximately 200,000 symptomatic patients in the U.S. alone [27]. - **Potential for Broader Applications**: The drug's mechanism may also be applicable to other inflammatory conditions, including COPD and IPF, due to its improved pharmacology and tolerability [43]. Financial Position - **Funding**: The company raised $138 million in a re-IPO, providing sufficient runway to conduct definitive studies in UC and Crohn's, with cash expected to last into 2029 [40]. Strategic Considerations - **Corporate Development**: The company is in early discussions with large pharmaceutical firms to raise awareness of its developments, preparing for potential partnerships as data becomes available [45]. Key Takeaways - **Innovative Approach**: PALI-2108's prodrug formulation represents a significant advancement in the treatment of inflammatory bowel diseases, aiming to improve patient tolerability and outcomes. - **Strong Pipeline**: The company is strategically positioned to address significant unmet needs in both UC and Crohn's disease, with plans for future studies and potential expansion into other therapeutic areas. - **Robust Financial Backing**: The recent funding provides a solid foundation for ongoing clinical trials and development efforts, enhancing the company's prospects for success in the competitive biotech landscape.

Core Insights - Palisade Bio, Inc. presented new translational data for PALI-2108, a targeted oral PDE4 inhibitor prodrug, at the 21st Congress of the European Crohn's and Colitis Organization (ECCO) in Stockholm, demonstrating localized target engagement and early clinical response within seven days [1][2][10] Group 1: Clinical Findings - In a Phase 1b trial involving patients with moderate-to-severe ulcerative colitis (UC), PALI-2108 achieved a 100% clinical response rate, with 40% of patients reaching clinical remission as measured by the modified Mayo Score [5][9] - The treatment resulted in significant downregulation of inflammatory and fibrosis-associated gene expression programs, including suppression of TNF-α, JAK–STAT, NF-κB, MAPK, and TGF-β pathways [5][6] - Histologic improvements were observed alongside reductions in fecal calprotectin and high-sensitivity C-reactive protein (hsCRP) levels, indicating a decrease in inflammation [5][6] Group 2: Mechanism of Action - PALI-2108 is designed for localized delivery to the terminal ileum and colon, where it is bioactivated by bacterial enzymes, allowing for targeted PDE4 inhibition at sites of inflammation while minimizing systemic exposure [7][9] - The prodrug's pharmacological activity was confirmed through RNA sequencing and pathway analyses, which showed localized suppression of inflammatory signaling networks in colonic tissue, with peripheral immune profiles remaining largely unchanged [4][6] Group 3: Safety and Tolerability - The safety profile of PALI-2108 was encouraging, with no serious adverse events reported among the 89 subjects in the study, supporting its potential as a differentiated treatment option for inflammatory bowel diseases [1][9] - The localized pharmacology of PALI-2108 aims to improve tolerability by reducing common side effects associated with systemic PDE4 inhibitors, such as diarrhea, nausea, and headache [7][8] Group 4: Future Development - Palisade Bio is advancing PALI-2108 into a Phase 2 clinical study to evaluate clinical remission, response, and pharmacodynamic biomarkers over a 12-week period, with plans for an extension phase to assess maintenance of remission [10]

Core Insights - Palisade Bio, Inc. has appointed Dr. Bram Verstockt to its Clinical Advisory Board to enhance its Phase 2 development strategy for PALI-2108 in ulcerative colitis and fibrostenotic Crohn's disease [1][2] - The company plans to submit an Investigational New Drug (IND) application for PALI-2108 in ulcerative colitis in the first half of 2026 [1][8] Company Overview - Palisade Bio is a clinical-stage biopharmaceutical company focused on developing next-generation oral PDE4 inhibitor prodrugs aimed at chronic inflammatory and fibrotic diseases [11] - The lead program, PALI-2108, is designed for targeted delivery to the terminal ileum and colon, utilizing local bacterial bioactivation to convert the prodrug into an active PDE4 inhibitor [9][10] Clinical Development - PALI-2108 has shown a 100% clinical response in a Phase 1b trial for ulcerative colitis, with no serious adverse events reported [12] - The upcoming Phase 2 study will evaluate clinical remission, response, and pharmacodynamic biomarkers over a 12-week period, with an extension phase for maintenance of remission [13] Expert Contribution - Dr. Verstockt's expertise in inflammatory bowel disease and precision medicine will be crucial for optimizing patient selection, endpoint strategy, and disease monitoring in the Phase 2 studies [3][8] - His background in advanced imaging, biomarker integration, and multi-omics research will support the design of studies aimed at demonstrating durable efficacy and disease modification [3][6]

Company Overview - Palisade Bio, Inc. is a clinical-stage biopharmaceutical company focused on developing next-generation, once-daily oral PDE4 inhibitor prodrugs aimed at targeted delivery to the terminal ileum and colon [2][6] - The company's lead program, PALI-2108, is designed to improve pharmacology, tolerability, and convenience for patients with inflammatory and fibrotic diseases [6][7] Product Details - PALI-2108 is a once-daily oral prodrug that is pharmacologically inactive until it reaches the lower intestine, where it is activated by bacterial enzymes at sites of inflammation and fibrosis [5][7] - In a recent Phase 1b trial, PALI-2108 achieved a 100% clinical response in the ulcerative colitis (UC) cohort, with no serious adverse events reported [7] - The company is advancing towards a Phase 2 clinical study in UC, which will evaluate clinical remission, response, and pharmacodynamic biomarkers over 12 weeks [8] Upcoming Events - JD Finley, CEO, and Dr. Mitchell Jones, President and CMO, will participate in a virtual fireside chat at the Piper Sandler Virtual Novel Targets in Immunology Symposium on February 12, 2026 [2][3] - A live webcast of the presentation will be available on the company's website, with a replay accessible for a limited time [4]

Core Viewpoint - Palisade Bio, Inc. is advancing its clinical-stage biopharmaceutical product, PALI-2108, a once-daily oral PDE4 inhibitor prodrug aimed at treating inflammatory and fibrotic diseases, with a focus on targeted delivery to the terminal ileum and colon [2][6]. Group 1: Company Overview - Palisade Bio is a clinical-stage biopharmaceutical company focused on developing next-generation oral PDE4 inhibitor prodrugs to enhance pharmacology, tolerability, and convenience for patients [6]. - The company is committed to transforming established PDE4 biology into safer oral therapies for chronic inflammatory and fibrotic diseases through its differentiated prodrug platform [6]. Group 2: Product Details - PALI-2108 is designed for targeted delivery of PDE4 inhibition to the terminal ileum and colon, activated by local bacterial bioactivation, which minimizes systemic absorption and improves tolerability [5]. - In a Phase 1b trial, PALI-2108 demonstrated a 100% clinical response in the ulcerative colitis (UC) cohort, with no serious adverse events and favorable pharmacokinetics [7]. Group 3: Clinical Development - The company is progressing towards a Phase 2 clinical study in UC, which will evaluate clinical remission, response, and pharmacodynamic biomarkers over a 12-week period, including an extension phase for maintenance of remission [8]. - Early studies are being completed in fibrotic diseases to further assess PALI-2108's safety, pharmacology, and potential therapeutic benefits across inflammatory bowel disease indications [8].

Core Insights - Palisade Bio has appointed Dr. Laurent Peyrin-Biroulet and Dr. David T. Rubin to its Clinical Advisory Board, enhancing its clinical strategy as it advances PALI-2108 towards Phase 2 development in ulcerative colitis and fibrostenotic Crohn's disease [1][2] Company Overview - Palisade Bio, Inc. is a clinical-stage biopharmaceutical company focused on developing next-generation oral PDE4 inhibitor prodrugs aimed at targeted delivery to the terminal ileum and colon [1][10] - The lead program, PALI-2108, is designed for once-daily oral administration and is pharmacologically inactive until it reaches the lower intestine, where it is activated by bacterial enzymes [9][11] Clinical Development - PALI-2108 has shown a 100% clinical response in a Phase 1b trial for ulcerative colitis, with no serious adverse events reported [11] - The company plans to submit an IND for a Phase 2 clinical study in ulcerative colitis in the first half of 2026, focusing on clinical remission and pharmacodynamic biomarkers over a 12-week period [1][12] Advisory Board Expertise - Dr. Peyrin-Biroulet is a leading authority in inflammatory bowel disease, with over 1200 peer-reviewed publications and significant roles in major IBD organizations [4][5] - Dr. Rubin is recognized for his expertise in clinical trial design and has been instrumental in the development of numerous approved IBD therapies [7][8]

Core Insights - Palisade Bio, Inc. is advancing its lead program, PALI-2108, a gut-targeted PDE4 inhibitor for ulcerative colitis, with two abstracts selected for presentation at major IBD conferences in early 2026 [1][3][4] Group 1: Product Development - PALI-2108 is designed for local delivery of PDE4 inhibition specifically to the terminal ileum and colon, minimizing systemic exposure and enhancing therapeutic index [4][7] - The prodrug is activated in the lower intestine, allowing for sustained local exposure and once-daily dosing, which aims to improve tolerability compared to systemic PDE4 inhibitors [4][7] - In a Phase 1b trial, PALI-2108 achieved a 100% clinical response in the ulcerative colitis cohort, with no serious adverse events reported [7] Group 2: Clinical Engagement - The Crohn's & Colitis Congress 2026 will feature a poster presentation on PALI-2108's ability to restore immune-epithelial balance in ulcerative colitis [2] - The 21st Congress of ECCO will also showcase findings from a Phase 1a study demonstrating clinical, histologic, and biomarker improvements with PALI-2108 [3] - The company aims to engage with the global IBD community to discuss these findings and the potential of PALI-2108 [3] Group 3: Future Plans - Palisade Bio is preparing to initiate a Phase 2 clinical study in ulcerative colitis, focusing on clinical remission and pharmacodynamic biomarkers over a 12-week period [8] - The company is also planning studies in fibrostenotic Crohn's Disease to further evaluate PALI-2108's safety and therapeutic benefits [8]

Core Insights - Palisade Bio, Inc. is developing PALI-2108, the first and only PDE4 inhibitor designed for targeted delivery to the terminal ileum and colon, addressing unmet needs in ulcerative colitis (UC) and fibrostenotic Crohn's disease (FSCD) [1][7] - The Crohn's & Colitis Foundation has approved a strategic equity investment of up to $500,000 in Palisade to support the clinical development of PALI-2108 [1][2] Company Overview - Palisade Bio is a clinical-stage biopharmaceutical company focused on next-generation, once-daily oral PDE4 inhibitor prodrugs aimed at improving pharmacology, tolerability, and convenience for patients with inflammatory and fibrotic diseases [5][6] - The company is advancing PALI-2108 for moderate-to-severe UC and FSCD, with a recent Phase 1b trial showing a 100% clinical response in the UC cohort and no serious adverse events [7][8] Product Development - PALI-2108 is designed for local delivery of PDE4 inhibition, becoming active only in the lower intestine, which minimizes systemic exposure and enhances therapeutic effects [3][7] - The company has completed several Phase 1 studies and is preparing for Phase 2 Investigational New Drug (IND) submissions to the FDA in 2026 [2][8]

Core Viewpoint - Palisade Bio, Inc. is advancing PALI-2108, a unique PDE4 inhibitor designed for targeted delivery to the terminal ileum and colon, addressing significant unmet needs in ulcerative colitis (UC) and fibrostenotic Crohn's disease (FSCD) [1][2] Investment and Support - The Crohn's & Colitis Foundation has approved a strategic equity investment of up to $500,000 in Palisade to support the clinical development of PALI-2108 [1][2] - This investment is seen as a strong endorsement of the scientific rationale behind PALI-2108 and its targeted approach to PDE4 inhibition [2] Clinical Development - Palisade has completed several studies, including a Phase 1a and Phase 1b cohort study in UC, and is currently evaluating PALI-2108 in an ongoing Phase 1b cohort study in FSCD [1][3] - Data from these studies are expected to support Phase 2 Investigational New Drug (IND) submissions to the FDA in 2026 [1] Product Characteristics - PALI-2108 is an orally administered prodrug that is gut-restricted and pharmacologically inactive until it reaches the lower intestine, where it is activated by bacterial enzymes [3] - The design allows for sustained local exposure, longer half-life, and once-daily dosing, aiming to maximize anti-inflammatory effects while minimizing systemic exposure [3] Clinical Efficacy - In a recent Phase 1b trial, PALI-2108 achieved a 100% clinical response in the UC cohort, with no serious adverse events reported [7] - The company is preparing for a Phase 2 clinical study in UC to evaluate clinical remission and response over 12 weeks [8]

Market Performance - U.S. stocks experienced gains, with the Dow Jones index increasing by 1.66% to 49,183.51, the NASDAQ rising by 0.80% to 23,420.85, and the S&P 500 up by 0.81% to 6,913.76 [1] - European shares also saw positive movement, with the eurozone's STOXX 600 gaining 0.94%, Spain's IBEX 35 Index rising by 0.70%, London's FTSE 100 up by 0.54%, Germany's DAX increasing by 1.34%, and France's CAC 40 climbing by 0.20% [5] - Asian markets closed mostly higher, highlighted by Japan's Nikkei 225 gaining 2.97% and China's Shanghai Composite surging 1.38%, while India's BSE Sensex fell by 0.38% [6] Commodity Prices - In commodity trading, oil prices increased by 1.7% to $58.30, gold rose by 2.9% to $4,454.40, silver surged by 7.3% to $76.230, and copper climbed by 5.1% to $5.9815 [4] Company Developments - Momentus Inc (NASDAQ:MNTS) shares surged by 57% to $8.98 following the announcement of an additive-manufactured fuel tank for flight testing [8] - GH Research PLC (NASDAQ:GHRS) shares increased by 17% to $15.43 after the FDA lifted the clinical hold on its Investigational New Drug Application for GH001 [8] - VerifyMe Inc (NASDAQ:VRME) shares rose by 66% to $1.12 due to a strategic merger letter of intent with Open World [8] - Zenas Biopharma Inc (NASDAQ:ZBIO) shares dropped by 57% to $14.94 after announcing results from the Phase 3 INDIGO trial [8] - Palisade Bio Inc (NASDAQ:PALI) shares fell by 16% to $2.10, and Palvella Therapeutics Inc (NASDAQ:PVLA) decreased by 14% to $86.16 [8] Economic Indicators - The ISM manufacturing PMI declined for the third consecutive month to 47.9 in December, marking the lowest reading since October 2024, down from 48.2 in November and below market estimates of 48.3 [2][7]