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. is advancing its clinical-stage biopharmaceutical product PALI-2108 for the treatment of Ulcerative Colitis, with positive preliminary data from its Phase 1a/b study indicating safety and tolerability [2][4][5] - The company has completed five single ascending dose (SAD) cohorts and the first three of four multiple ascending dose (MAD) cohorts, reporting no serious adverse events (SAEs) or treatment-emergent adverse events (TEAEs) related to laboratory values or EKGs [1][3][4] - Topline data is expected to be reported in the first half of 2025, aligning with management's expectations [4][5] Study Details - The Phase 1a/b study aims to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of PALI-2108 in both healthy volunteers and patients with Ulcerative Colitis [5] - Biomarkers such as serum high sensitivity C-reactive protein (hsCRP) and fecal calprotectin (CalPro) will be utilized to assess the drug's effects, alongside histological assessments of colonic tissue [5] - PALI-2108 is a new chemical entity that has not been previously administered to humans, differentiating it from other PDE4 inhibitors that have received market approval [5] Company Overview - Palisade Bio is focused on developing novel therapeutics for patients with autoimmune, inflammatory, and fibrotic diseases, aiming to transform the treatment landscape through targeted approaches [7]