Summary of Palisade Bio FY Conference Call Company Overview - **Company**: Palisade Bio (NasdaqCM:PALI) - **Industry**: Biotechnology, specifically focusing on treatments for inflammatory bowel disease (IBD) including ulcerative colitis (UC) and fibrostenotic Crohn's disease Key Milestones and Catalysts - Completion of a Phase 1B cohort in fibrostenotic Crohn's disease with results expected in early Q1 2026 [6] - Filing of an Investigational New Drug (IND) application for a definitive UC study, anticipated to start mid-year 2026 [6][7] - Final top-line readout for the UC study scheduled for the end of 2027 [7] Product Mechanism and Differentiation - **Product**: PALI-2108, a PDE4 inhibitor designed as a prodrug for optimized local delivery in the gut [9] - Unique formulation allows for once-daily dosing, targeting the terminal ileum and colon, which is not available with other PDE4 inhibitors [11] - The prodrug is activated by gut bacteria, minimizing systemic exposure and associated adverse effects [11][12] - Demonstrated 100% clinical response and 40% clinical remission in a small cohort of UC patients after one week of treatment [24] Clinical Data and Efficacy - Historical data shows a 31% clinical remission rate for Apremilast and a 57% rate for Mefenilast, while PALI-2108 showed a 100% clinical response in a five-patient cohort [14][15] - Significant biomarker improvements observed: 70% reduction in fecal calprotectin, 15% reduction in CRP, and a 70% increase in cyclic AMP after one week of treatment [15] - The drug is reported to be 20 times more potent than Apremilast, allowing for higher dosing without increased toxicity [17] Safety and Tolerability - Emphasis on safety and tolerability as key differentiators in the market, especially compared to JAK inhibitors and S1Ps which have safety warnings [22][37] - Ongoing studies aim to demonstrate safety and tolerability in symptomatic fibrostenotic Crohn's patients with ileal lesions [44] Future Development Plans - Phase 2 study design includes 195 patients with a focus on individual patient dosing adaptation after the first three weeks [30] - The study aims to establish safety, tolerability, and efficacy, with potential for accelerated approval based on surrogate biomarkers [49] - Current cash position is strong with $138 million raised, providing sufficient runway for Phase 2 studies in both UC and fibrostenotic Crohn's disease [50] Market Opportunity - High unmet medical need in fibrostenotic Crohn's disease with limited competition and no current approvals for anti-inflammatory, antifibrotic treatments [42][43] - The company is positioned uniquely as the only candidate targeting both anti-inflammatory and antifibrotic pathways in this indication [43] Conclusion - Palisade Bio is poised for significant developments in 2026 with promising clinical data, a strong financial position, and a unique product offering that addresses critical needs in the treatment of IBD [51]

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]