Core Insights - PALI-2108 has shown safety and tolerability with no serious adverse events, supporting its potential as a once-daily oral therapy for ulcerative colitis and fibrostenotic Crohn's disease [1][2][3] Clinical Data Summary - Phase 1b study demonstrated a 100% clinical response rate in patients with moderate-to-severe ulcerative colitis, with significant histological and biomarker improvements [2][4] - Key findings from the Phase 1b study include a mean reduction of 62.8% in the modified Mayo score and a decrease in fecal calprotectin in 4 out of 5 patients [4] - Phase 1a study confirmed extended drug exposure with colon tissue drug concentrations remaining above target levels for over 36 hours post-dose, supporting a once-daily dosing regimen [5][10] Mechanism of Action - PALI-2108 is designed to selectively inhibit PDE4 in the distal ileum and colon, utilizing a microbiome-activated mechanism to enhance local bioactivation and minimize systemic exposure [7] - The drug demonstrated significant immunomodulatory effects, including a 40% average reduction in tissue lymphocytes and a 51% decrease in PDE4B expression [4][10] Future Development Plans - The company plans to submit an Investigational New Drug (IND) application for a Phase 2 study in the first half of 2026, following the completion of ongoing studies [1][5]

Summary of Palisade Bio (PALI) Conference Call - February 19, 2025 Company Overview - **Company**: Palisade Bio (PALI) - **Industry**: Biotechnology, specifically focusing on treatments for inflammatory bowel diseases (IBD) such as ulcerative colitis and Crohn's disease Core Points and Arguments 1. **Drug Development**: - PALI-2108 is a PDE4 inhibitor formulated as a prodrug, originally developed in Merck labs, designed to be more potent than previous inhibitors for treating ulcerative colitis and Crohn's disease [3][4] - The prodrug formulation minimizes systemic exposure, allowing the drug to reach the distal ileum in the colon, targeting the disease more effectively [4] 2. **Market Opportunity**: - Nearly 1 million patients in the U.S. suffer from ulcerative colitis, with 55% experiencing moderate to severe cases [5] - Current treatments have less than a 20% success rate and often come with poor safety profiles, highlighting the need for better options [5] 3. **Phase One Study Results**: - Preliminary data from the single ascending dose (SAD) study showed that PALI-2108 was well tolerated across all doses (15 mg to 450 mg) with no serious adverse events or treatment-related laboratory abnormalities [6] - Mild treatment-emergent adverse events were noted only at the highest dose, indicating a favorable safety profile [6] 4. **Market Size and Deal Activity**: - The global ulcerative colitis market is currently valued at over $7 billion and is projected to exceed $9 billion by 2028 [7] - There have been 70 deals in the IBD space over the last five years, with an average deal value of $1.2 billion, indicating strong investor interest and potential for growth [7][8] 5. **Second Drug Development**: - PALI-1908, another drug in development, utilizes the same active PDE4 inhibitor as PALI-2108 but is designed to release the drug in the terminal ileum, targeting fibrosis in Crohn's patients [9] - Initial data suggests that PALI-2108 may also be effective for treating fibrotic Crohn's disease, potentially reducing the need for a separate drug development process [9] Additional Important Information - The company emphasizes the importance of oral delivery for patient compliance and preference, which is a significant advantage over current treatment options [4] - The favorable safety profile and targeted delivery mechanism of PALI-2108 are expected to provide a competitive edge in the market [6][7] - The company plans to provide further updates on the development of PALI-2108 and its potential applications in treating Crohn's disease in the coming months [9]