Chemomab Therapeutics Ltd. · NASDAQ:CMMB
Chemomab Therapeutics — AASLD 2023
15 slides from Chemomab Therapeutics's conference presentation, 2023
Slide 1: Serum Proteomics Reveals Unique Association of CCL24 with Disease-related Pathways in PSC
Serum Proteomics Reveals Unique Association of CCL24 with Disease-related Pathways and Signatures in Primary Sclerosing Cholangitis Ilan Vaknin Presentation ID# 44663
Slide 2: Ilan Vaknin
Ilan Vaknin • VP of Research and Development at Chemomab Therapeutics Ltd | Immunologist with 20 years' experience in academia and biotech | PhD in Immunology from the Hebrew University, Postdoctoral Graduate from the Weissman Institute in Neuroscience. Slides are the property of the author and AASL
Slide 3: Disclosure and Forward-Looking Statements
Disclosure and Forward-Looking Statements • Presenter: Ilan Vaknin • I disclose the following financial relationship(s) with a commercial interest: • I work as VP R&D at Chemomab ltd, a Nasdaq traded company. • This presentation contains forward-looking statements that involve substantial risks and
Slide 4: CCL24's Dual Role in Inflammation and Fibrosis-related Pathology
CCL24’s Dual Role in Inflammation and Fibrosis-related Pathology CCL24 THE POWER OF CCL24 The Target CCR3 Dual Role in Promoting Fibrosis & The Receptor Inflammation CCL24 CCL24 Directly activates fibroblasts Regulated Cells Regulated Cells Enhances local immune cell recruitment Differentiated Activ
Slide 5: CM-101 Neutralizes CCL24 and Reduces Inflammation and Fibrosis
CM-101 Neutralizes CCL24 and Reduces Inflammation and Fibrosis CM-101 The Antibody CCL24 CM-101 Reduces In The Target CM-101 Inhibits Vivo Monocyte Primary Fibroblast Recruitment CCR3 Activation The CCL24 Receptor CCL24 Regulated Cells Regulated Cells Proliferation: Relative Change 1.8 10 Monocytes
Slide 6: Clinical Relevance of CM-101 Supported by Elevated CCL24 Levels in PSC Patients
Clinical Relevance of CM-101 Supported by Elevated CCL24 Levels in PSC Patients CCL24 LEVEL IN HEALTHY VS PSC PATIENT LIVER TISSUE CCL24 AND CCR3 EXPRESSION IN PSC PATIENT LIVER TISSUE Healthy Liver PSC Livers CCL24 Staining CCL24 in Nonlobular Areas Iba1+/CCL24+ a-SMA+/ CCR3+ ✱ ✱✱ 6 ✱ Cell Density
Slide 7: CM-101 Reduces Liver Injury & Fibrosis in Multiple PSC Animal Models
CM-101 Reduces Liver Injury & Fibrosis in Multiple PSC Animal Models Mdr2-/- MOUSE CHOLANGITIS MODEL Mdr2 -/- Mdr2 -/- + CM-101 % FIBROSIS Collagen SIRIUS RED (COLLAGEN) (SIRIUS RED STAINING) % Fibrosis Expression 15 1.5 100 10 1.0 80 60 82% reduction 5 0.5 40 0 0.0 Mdr2 -/- Mdr2 -/- Mdr2-/- Mdr2-/-
Slide 8: Serum Proteomics to Reveal Disease-Related Pathways
Serum Proteomics to Reveal Disease-Related Pathways Serum • Canonical pathways • Upstream regulators • Liver-related toxicity functions HC PSC Proteomics N = 30 N = 45 Olink Explore 3072 20 Healthy controls PSC, high ELF 3 Comparison Groups: 0 PSC, low ELF • Disease (PSC vs HC) PC2 • Fibrosis Severi
Slide 9: Disease-Related Canonical Pathways Are Elevated in Patients with High CCL24 Levels
Disease-Related Canonical Pathways Are Elevated in Patients with High CCL24 Levels Overlapping Pathways # Top 30 pathways Whitin a Given Pathway (NPX) Mean Expression of Proteins Top Overlapping pathways: [1] Pathogen Induced Cytokine Storm Signaling Pathway [2] Granulocyte Adhesion and Diapedesis [
Slide 10: Disease-Related Upstream Regulators Are Elevated in Patients with High CCL24 Levels
Disease-Related Upstream Regulators Are Elevated in Patients with High CCL24 Levels Overlapping Regulators # Top 20 regulators Whitin a Given Pathway (NPX) Mean Expression of Proteins Overlapping regulators: [1] TNF [6] IL1B [2] IFNG [7] IL10 [3] IL4 [8] IL6 [4] TGFB1 [9] STAT3 [5] Immunoglobulin HC
Slide 11: Disease-Related Toxicity-Functions Are Elevated in Patients with High CCL24 Levels
Disease-Related Toxicity-Functions Are Elevated in Patients with High CCL24 Levels Overlapping Toxicities # Whitin a Given Pathway (NPX) Mean Expression of Proteins Overlapping toxicity functions: [1] Degeneration of liver [7] Liver Hyperplasia/Hyperproliferation [2] Hepatocellular carcinoma [8] Liv
Slide 12: Unique Association of CCL24 with Key Disease-Related Pathways and Regulators
Unique Association of CCL24 with Key Disease-Related Pathways and Regulators CCL24 levels CCL11 levels CCL26 levels Hepatic Fibrosis Pathway CCL11 CCL24 CCL26 (Eotaxin-1) (Eotaxin-2) (Eotaxin-3) IFNγ Regulator Inflammation Tox-Function Liver CCR3 ns, nonsignificant, * p<0.05, **p<0.01; Welch 2-sampl
Slide 13: CM-101 Phase 2 Trial in Primary Sclerosing Cholangitis
CM-101 Phase 2 Trial in Primary Sclerosing Cholangitis Key Enrollment Criteria CM-101-PSC-101 PSC patients with large duct disease of >24 weeks duration • ALP > 1.5 ULN • Stable IBD allowed CM-101 10 mg/kg CM-101 10 mg/kg • Stable UDCA treatment allowed IV Q3W (n~25) IV Q3W Screening Outcome Measure
Slide 14: Key Takeaways
Key Takeaways • CCL24 is associated with both inflammatory and • CM-101 Reduces Liver Injury & Fibrosis in Multiple PSC Animal fibrotic mechanisms Models • Preclinical and patient • Disease-related canonical pathways, upstream regulators derived serum proteomics and toxicity-functions are elevated d
Slide 15: Thank you!
Dr . Francesca Saffioti Prof. Douglas Thorburn Prof. Massimo Pinzani UCL Institute of Immunity & Transplantation, United Kingdom Thank you!