Chemomab Therapeutics Ltd. · NASDAQ:CMMB
Chemomab Therapeutics — EASL 2022
19 slides from Chemomab Therapeutics's conference presentation, June 2022
Slide 1: Whole Liver Single Cell RNA Sequencing and Spatial Transcriptomics Reveal CCL24-Regulated Pathways
Combination of Whole Liver Single Cell RNA Sequencing and Spatial Transcriptomics Reveals Specific Cell Sub-Populations and Pathways Regulated by CCL24 June 2022
Slide 2: CCL24 is a Novel Therapeutic Target for Fibrosis
CCL24 is a Novel Therapeutic Target for Fibrosis Critical Mediator Promoting Inflammation and Fibrosis CCL24-secreting cells M2 Macrophages, Immune and Epithelial cells Dual role in promoting fibrosis CCL24-regulated cells CCL24 Fibroblasts-Liver, Lung and skin, - directly activates fibroblasts Im
Slide 3: CM-101: First-in-Class mAb Blocking CCL24
CM-101: First-in-Class mAb Blocking CCL24 CM-101 CM-101 Reduces In vivo CM-101 Inhibits Primary Hepatic Monocyte Recruitment CCL24 Fibroblast Proliferation CCR3 Inflammation Fibrosis Immune cell Fibroblast activation recruitment & proliferation CM-101 attenuates inflammation and fibrosis by inhibiti
Slide 4: Primary Sclerosing Cholangitis (PSC)
Primary Sclerosing Cholangitis (PSC) o Chronic bile duct inflammatory and fibrotic disease leading to end-stage liver disease and cirrhosis o 70% of PSC patients have concomitant inflammatory bowel disease o No FDA approved drug o Median Survival of 10-12 years with no intervention o ~70K PSC patien
Slide 5: CCL24 and CCR3 are Highly Expressed in PSC Patients' Liver Biopsies
CCL24 and CCR3 are Highly Expressed in PSC Patients’ Liver Biopsies CCL24 CCL24 CCR3 o High CCL24 expression in biliary epithelial cells (BEC) and immune cells (including macrophages) o High CCR3 expression in BEC, immune cells and hepatic stellate cells (HSC) o High serum CCL24 levels correlate wit
Slide 6: CM-101 Decreases Liver Fibrosis and Biliary Mass in the Mdr2-/- PSC Model
CM-101 Decreases Liver Fibrosis and Biliary Mass in the Mdr2-/- PSC Model o Mdr2-/- mice develop similar PSC features in terms of cholangitis, severe ductular reaction and fibrosis o CM-101 (D8) treatment (10 mg/kg) reduces serum levels of ALP, bile acids and ALT o CM-101 (D8) treatment (10 mg/kg) r
Slide 7: Studying CCL24 Pathways Using Two Complementary High-Throughput Methods
Studying CCL24 Pathways Using Two Complementary High-Throughput Methods Single cell RNA Spatial sequencing (scRNA-seq) transcriptomics Adopted from de Vries et al, Front Oncol 2020
Slide 8: scRNA-seq of Mdr2-/- Liver Identifies Five Populations of Mononuclear Phagocytes
scRNA-seq of Mdr2-/- Liver Identifies Five Populations of Mononuclear Phagocytes Aif1 (Iba1) CD68 UMAP2 UMAP1 Adgre1 (F4/80)
Slide 9: Spatial Transcriptomics of the Damaged Periductal Area of Mdr2-/- Mice
Spatial Transcriptomics of the Damaged Periductal Area of Mdr2-/- Mice Stain Segment periductal area Collect oligos Count cholangiocytes PanCK / F4/80 (PanCK+) Non-cholangiocytes (PanCK-) 100μM PanCK – BEC F4/80 - macrophages NanoString Technologies N = 12 ROIs, 4 mice
Slide 10: Combination of scRNA-seq and Spatial Transcriptomics Identifies Kupffer Cells
Combination of scRNA-seq and Spatial Transcriptomics Identifies Kupffer Cells in the Injured Peribiliary Area scRNA-seq Spatial Transcriptomics 40 Cluster specific gene expression KC 35 Normalized Counts 30 Mono 25 Mo-MF 20 DC 15 10 5 0 KC T cells Mono & DC KC – Kupffer cells Mo-MF Mono – monocytes
Slide 11: CM-101 Reduces Type 2 Dendritic Cells in the Peribiliary Area
CM-101 Reduces Type 2 Dendritic Cells in the Peribiliary Area scRNA-seq Spatial Transcriptomics (cell deconvolution) 8 Mdr2-/- Mdr2 -/- + CM-101 ✱ Mdr2-/- CM-101 ✱ + vehicle 6 Mdr2 -/- vehicle 4 % 2 cDC1 – classical type 1 dendritic DC-SIGN Ccr7 cells 0 cDC2 – classical 2 1 type 2 dendritic pe pe ce
Slide 12: CM-101 Reduces Macrophage and Monocyte Recruitment to the Peribiliary Area
CM-101 Reduces Macrophage and Monocyte Recruitment to the Peribiliary Area scRNA-seq Spatial Transcriptomics (cell deconvolution) Monocytes Macrophages g ✱ 3 ✱ 3 2 2 % % 1 1 Cd14 Cx3cr1 0 0 -1 /- hi -/- -1 /- hi -/- - - 01 e 2 ve r2 01 e 2 ve r2 cl dr cl dr d d M M M M M M C C H2-M2 (MHCII) Ccr2 Nan
Slide 13: CCL24 is Expressed by Two Resident Liver Macrophage Populations
CCL24 is Expressed by Two Resident Liver Macrophage Populations Cd163 Clec4f Marco Kdr (VEGFR2) Lyve1 Ccl24
Slide 14: CM-101 Treatment Reduces ECM Formation Pathways in Peribiliary PanCK- Populations
CM-101 Treatment Reduces ECM Formation Pathways in Peribiliary PanCK- Populations Differentially Expressed Genes Gene Set Enrichment Analysis Downregulated Upregulated Downregulated Upregulated Collagen formation pathways
Slide 15: CM-101 Treatment Reduces Cholangiocyte Senescence and Proliferation
CM-101 Treatment Reduces Cholangiocyte Senescence and Proliferation Differentially Expressed Genes Gene Set Enrichment Analysis Downregulated Upregulated -2 -1 0 1 2 Normalized enrichment score (NES) Downregulated Upregulated Senescence pathways Mitosis pathways
Slide 16: CM-101 Treatment Reduces Expression of Inflammatory and ECM Genes in Cholangiocytes
Normalized Counts 0 5 10 15 20 M d C r2 M -1 -/- 01 M ✱ d Normalized Counts 0 20 40 60 ve r2 - Col1A2 hi /- cl M dr e C 2 M -1 -/- 01 M ✱ d Normalized Counts CCL2 ve r2 - 0 10 20 30 40 50 hi /- cl M e dr C M 2 -/ -1 - 01 M ✱✱ d ve r2 - Col4A1 h i /- cl e Normalized Counts 0 2 4 6 M d C r2 M -1 -/- N
Slide 17: Summary
Summary o Combination of single-cell and spatial transcriptomics CM-101 methods enabled in depth analysis of relevant sub- populations and pathways o Kupffer-cells and a novel population of resident-like CCL24 macrophages identified as CCL24 main secreting cells CCR3 o Resident macrophages were foun
Slide 18: Acknowledgements
Acknowledgements Chemomab Ltd. NanoString Technologies Adi Mor David Scoville Michal Segal-Salto Anthony Zucca Neta Barashi Yan Liang Avi Katav Massimo Cerfeda Omer Levi Hadassah Medical Center, Jerusalem Amnon Peled Inbal Mishalian Devorah Olam Ophir Hay Bioinformatics unit (scRNA-seq) Sharona Elga
Slide 19: Thank you
Thank you Presentation name