Palisade Bio, Inc. · NASDAQ:PALI
Palisade Bio — 8th Anti-Fibrotic Drug Development Summit (November 2024)
17 slides from Palisade Bio's conference presentation, November 2024
Slide 1: Detailing Characteristics of Fibrostenotic Crohn's Disease Biology & Local PDE4 Inhibitor Prodrug
Detailing Characteristics of Fibrostenotic Crohn’s Disease Biology & the Potential of a Local PDE4 Inhibitor Prodrug to Minimize Off-Target Effects & Maximize Efficacy Mitch Jones, MD, PhD 8th Anti-Fibrotic Drug Development Summit November 2024
Slide 2: Forward Looking Statements
Forward Looking Statements 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
Slide 3: Introduction to IBD and Fibrosis
Introduction to IBD and Fibrosis • IBD Overview: • Includes Crohn’s disease (CD) and ulcerative colitis (UC). • Commonly accompanied by intestinal fibrosis. • Currently, there are no specific treatments. • Symptoms Associated with Fibrosis: • CD: Strictures and obstructive symptoms. • UC: Urgency an
Slide 4: Mechanisms of Intestinal Fibrogenesis
Mechanisms of Intestinal Fibrogenesis • Extra Cellular Matrix (ECM) Deposition and Scar Formation: • One of the hallmark features of IBD. • Physiological process for tissue repair. • Excessive ECM causes tissue stiffness and functional impairment. • Intestinal fibrosis is present even without strict
Slide 5: Mesenchymal cells Drive Intestinal Fibrosis
Mesenchymal cells Drive Intestinal Fibrosis • Intestinal Mesenchymal Cells: • Non-epithelial, non-endothelial, non-hematopoietic. • Provide scaffold for tissue structure. • Fibroblasts, Myofibroblasts, and SMCs: • Differentiation markers and these transition between phenotypes in inflamed intestine.
Slide 6: Fibroblast-Activating Mediators in Intestinal Fibrosis
Fibroblast-Activating Mediators in Intestinal Fibrosis • Complex Microenvironment: • Mesenchymal cells exposed to luminal contents and inflammatory mediators. • Critical for initiation and perpetuation of IF. • Observations: • Location of strictures follows the location of disease. • Degree of fibro
Slide 7: Key Mediators of Intestinal Fibrosis
Key Mediators of Intestinal Fibrosis • TGF-β1: • IL-34 • Dominant profibrotic growth factor. • Constitutively expressed in int/colon. • Upregulated in fibrotic diseases, including CD. • Higher expression level in structuring CD. • Upregulates α-SMA, collagen I, and fibronectin. • Direct activator of
Slide 8: PDE4 is an Important Target which Affects Multiple Mediators of Intestinal Fibrosis
PDE4 is an Important Target which Affects Multiple Mediators of Intestinal Fibrosis • Patients with Intestinal Fibrosis show increased levels of PDE4 enzymes in intestinal tissues. • Mouse models of IF have been used to demonstrate PDE4 inhibitors significantly improve disease activity. • PDE4 inhib
Slide 9: PALI-2108: Mechanism of Action
ee PALI-2108: Mechanism of Action © : 2 Bacterial Z @: © 29 = enzyme SUPERIOR TNF-a : . m ene e PALI-2108 PALI-0008 PDE4 INHIBITOR PRODRUG —_PDE4INHIBITORW | BLOCKING PROFILE , * - mm se ; 7 eaghec*t ACTIVATION -* Pre ire? * e ; : a : - @¢ 5 ‘ T cell ~~ oe , ae: ” = Ss od ie % Monocyte | 3 | * m2 Gh
Slide 10: Limited Systematic Activity in Preclinical Model Provides Potential for Improved Safety Profile
PALI-2108 Limited Systematic Activity in Preclinical Model Provides Potential for Improved Safety Profile Lack of Plasma Activity is Believed to Mitigate CNS Side Effects, like Nausea, Which is Seen with Systemic PDE4 Inhibitors PALI-0008 (active form) PALI-0708 (inactive metabolite) Prodrug is re
Slide 11: Demonstrated Improved Efficacy Over Standard of Care and Systematic PDE4 Inhibitors in DSS Colitis
PALI-2108 Demonstrated Improved Efficacy Over Standard of Care and Systematic PDE4 Inhibitors in DSS Colitis Mouse Model Dose Dependent Efficacy Response in PALI-2108 demonstrated clear Two DSS Colitis Mouse Models dose dependent improvements in clinical outcome measures and was better than SOC in D
Slide 12: Demonstrated Improved Efficacy Over Standard of Care and Systematic PDE4 Inhibitors in DSS Colitis
PALI-2108 Demonstrated Improved Efficacy Over Standard of Care and Systematic PDE4 Inhibitors in DSS Colitis Mouse Model Dose Dependent Efficacy Response in DSS Colitis Mouse Model Colon tissue PDE4B Expression (mRNA) was reduced in response Fold Change Relative to Naive to PALI-2108 in a dose depen
Slide 13: Prominent markers from meta-analysis are associated with fibrotic pathways
PALI-2108 Prominent markers from meta-analysis are associated with fibrotic pathways We built a >1,600 UC and CD patient database including patients with ileal and colon tissue RNAseq data and built a genomics workflow to identify markers and enriched pathways of fibrosis in UC and CD We included ge
Slide 14: Demonstrated Dose Response for Engagement of Most Important Fibrotic Pathways in UC and Crohn's
PALI-2108 Demonstrated Dose Response for Engagement of Most Important Fibrotic Pathways in UC and Crohn’s PALI-2108 demonstrated localized bioactivation Engagement of genes from the four IBD fibrotic pathways (187 genes) and potent antifibrotic pathway engagement Consolidated enrichment score for th
Slide 15: Palisade Bio
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Slide 16: Precision Medicine-Based Approach
Precision Medicine-Based Approach Machine Learning Technology for Patient Selection Targeting patients with elevated PDE4 activity (PDE4 related biomarkers) to potentially enhance responder population Process Identify Markers Top Ranked Top Ranked in Relation with RNAseq DiffExp of Colitis Genes (U
Slide 17: First Precision Medicine Test with PDE4B-Based Selection Alone Could be a Breakthrough
PALI-2108 First Precision Medicine Test with PDE4B-Based Selection Alone Could be a Breakthrough Elevated PDE4B Expression: Consistently observed in adult patients in >1600 patients and ~10 studies Broad Applicability: Average expression of 1.6 TPM (range 0.8- 2.81 TPM) covers over 70% of moderate t
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