Summary of Palisade Bio Conference Call - March 31, 2026 Company Overview - **Company**: Palisade Bio (NasdaqCM:PALI) - **Focus**: Development of PALI-2108, a next-generation therapy for Crohn's disease targeting both inflammation and fibrosis Key Industry Insights - **Crohn's Disease**: A progressive inflammatory bowel disease characterized by relapsing/remitting symptoms, often leading to structural damage and complications requiring surgical intervention - **Current Treatment Landscape**: Existing therapies often fail to address fibrosis, a significant challenge in treating advanced Crohn's disease Core Findings from the Conference Call 1. **PALI-2108 Phase I-B Trial Results**: - Achieved safety and tolerability over two weeks of dosing in patients with fibrostenotic Crohn's disease [5][6] - Demonstrated once-daily dosing capability while maintaining necessary drug levels in tissue and plasma [6] - Positive movement in biomarkers such as fecal calprotectin and SES-CD scores, indicating potential biological effects [7][9] 2. **Clinical Efficacy**: - 40% of patients achieved endoscopic response and remission after two weeks [27] - Mean absolute reduction in SES-CD score of 3.8 points, representing a 47.5% improvement over baseline [27] - Results are favorable compared to established therapies, suggesting PALI-2108's potential in broader Crohn's populations [28] 3. **Strategic Developments**: - Completed $138 million financing, enabling further development and visibility in the gastroenterology community [10] - Strengthened clinical advisory board with experts in inflammatory bowel disease (IBD) [11][12] 4. **Regulatory Pathway**: - Focus on luminal Crohn's disease due to clearer regulatory pathways and larger patient population [36][37] - Future studies may include fibrostenotic Crohn's disease as regulatory paths are established [39] 5. **Safety Profile**: - No serious adverse events reported; PALI-2108 was well tolerated with no PDE4-related side effects [31] - Safety differentiates PALI-2108 from traditional PDE4 inhibitors, which often have significant side effects [31] Additional Insights - **Market Need**: There is a significant unmet need for effective oral therapies targeting both inflammation and fibrosis in Crohn's disease [14][15] - **Mechanism of Action**: PALI-2108 is a gut-activated prodrug with dual anti-inflammatory and anti-fibrotic properties, potentially improving patient outcomes [20][23] - **Future Directions**: Plans to assess efficacy in moderate to severe Crohn's disease and explore antifibrotic effects earlier in the disease course [32] Conclusion - The data presented during the call indicates promising early results for PALI-2108 in treating fibrostenotic Crohn's disease, with a focus on safety, efficacy, and a clear regulatory pathway for future studies. The company is positioned to address significant unmet needs in the IBD market, with ongoing efforts to expand its clinical trials and enhance its visibility within the healthcare community.

NASDAQ: PALI palisadebio.com Phase 1b in Fibrostenotic Crohn's Disease March 31, 2026 Statements in this presentation that are not statements of historical fact are forward-looking statements. Such forward-looking statements include, without limitation, statements regarding our research and pre-clinical and clinical development plans, expected near and long-term milestones, hypothesis related to PALI-2108, the potential of PALI-2108 to treat inflammatory bowel disease ("IBD"), our ability to successfully co ...

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]