Anti-CCL24 Therapeutic Platform

Introduction

Chemomab's R&D talent, infrastructure and capabilities support early-stage discovery through clinical development. Our R&D team is investigating underlying fibro-inflammatory biology via a broad range of in-vitro and in-vivo models, which provide the foundation for development of potentially transformative patient therapeutics.

Chemomab leverages collaborations with leading investigators from prestigious research centers around the world to obtain further evidence on CCL24’s unique role in fibrosis and demonstrate CM-101’s potential anti-fibrotic and anti-inflammatory therapeutic effects.

The Roles of CCL24 and CM-101

CCL24 Recruits Immune Cells

CCL24 promotes inflammation by recruiting immune cells from circulation to the injured tissue

CCL24 Activates Fibroblasts

CCL24 stimulates the transition of fibroblasts to myofibroblasts and elevates production and secretion of the extracellular matrix

CM-101 Attenuates Fibrosis and Inflammation

CM-101 binds to CCL24, attenuating its pro-inflammatory and pro-fibrotic activities, which improves the injured tissues’ inflammatory-fibrotic damage

  • Immune cell

  • CCL24

  • Fibroblast

  • Activated fibroblast

  • CM-101

About CCL24

Over the last decade, our scientific team discovered the role of CCL24 as a key regulator in fibro-inflammatory processes, specifically, the pivotal pro-fibrotic and pro-inflammatory effects of CCL24 in fibrotic diseases.

Chemomab observed CCL24 up-regulation and its correlation with disease severity in fibrotic disease tissues, including liver, skin and lung fibrosis related pathologies (e.g. PSC, SSc).

Based on these discoveries, Chemomab established a comprehensive preclinical package to support the therapeutic effects of blockading CCL24.

We demonstrated that CCL24 works through a dual biological pathway directly activating fibroblasts while recruiting immune cells and thereby maintaining the inflammatory environment that supports fibrogenesis.

Chemomab has showed that inhibiting these pathways by blocking CCL24 prevents and reverses fibrotic tissue growth within the liver, skin and lung.

Based on patient data and relevant disease models, Chemomab developed CM-101, a first-in-class monoclonal antibody that targets CCL24 and blocks its downstream pathways.

About CM-101

CM-101 is a novel therapy that addresses the high unmet need for effective treatments for fibrotic diseases. In preclinical studies, treatment with CM-101 demonstrated strong anti-fibrotic effects, reduced inflammatory injury and significantly improved organ damage. Numerous in-vivo, in-vitro and ex-vivo studies showed that CM-101 demonstrated potent anti-CCL24 effects in disease models of PSC, SSc, idiopathic pulmonary fibrosis (IPF) and NASH.

CM-101 appears safe and well tolerated in healthy subjects and in fatty liver disease and NASH patients with both intravenous and subcutaneous administrations.

Based on CM-101’s broad, robust biological effects, favorable tolerability profile and unique mechanism of action, Chemomab believes CM-101 may have the potential to interrupt the deleterious pathological processes that drive fibrosis, with the potential to become a effective anti-fibrotic therapeutic agent.

A Phase 2a liver fibrosis trial of CM-101 in NASH patients has been completed. In this study, CM-101-was safe and well-tolerated and treated patients showed consistent and positive improvements across a number of fibro-inflammatory biomarkers that are relevant to NASH and to additional fibro-inflammatory diseases. The Phase 2 SPRING trial of CM-101 for the treatment of primary sclerosing cholangitis has completed patient enrollment, with a topline data readout expected midyear 2024. The CM-101 SSc program has an open U.S. IND and is Phase 2-ready.

Publications

  1. The role of CCL24 in primary sclerosing cholangitis: bridging patient serum proteomics to preclinical data

    Greenman, R.; et al. The Role of CCL24 in Primary Sclerosing Cholangitis: Bridging Patient Serum Proteomics to Preclinical Data. Cells 2024, 13, 209
  2. CCL24 regulates biliary inflammation and fibrosis in primary sclerosing cholangitis

    Mor et al. JCI Insight. 2023: 8(12): e162270
  3. The role of CCL24 in systemic sclerosis

    Levy H, et al. The Role of CCL24 in Systemic Sclerosis. Rambam Maimonides Med J 2023;14 (3):e0016
  4. A blocking monoclonal antibody to CCL24 alleviates liver fibrosis and inflammation in experimental models of liver damage

    Segal-Salto et al. JHEP Rep. 2020 Jan 2;2(1):100064
  5. Blockade of CCL24 with a monoclonal antibody ameliorates experimental dermal and pulmonary fibrosis

    Mor et al. Ann Rheum Dis 2019;78:1260–1268
  6. Eotaxin-2 blockade ameliorates experimental autoimmune encephalomyelitis

    Mausner-Fainberg et al. World J. Immunol. 2013 Mar; 3(1):7-14.
  7. Anti eotaxin-2 antibodies attenuate the initiation and progression of experimental atherosclerosis

    Mor et al. World J. Cardiovascular Dis. 2013; 3:339-46
  8. Protective effect of eotaxin-2 inhibition in adjuvant-induced arthritis

    Ablin et al. Clinical and Experimental Immunology. 2010; V161(2):276–83

Posters

  1. EASL 2024 - Ex-vivo translational assay of hepatic stellate cells using patient-derived serum characterizes the anti-fibrotic activity of CM-101

  2. EASL 2024 - Machine learning-driven identification of serum protein signature for primary sclerosing cholangitis and enhanced liver fibrosis score

  3. Gordon Research Conference on Chemotactic Cytokines - Attenuating liver fibrosis and inflammation: blocking CCL24 inhibits recruitment of hepatic stellate cells, monocytes and neutrophils and modulates hepatic stellate cell activation

  4. ACR Convergence 2023-The involvement of CCR3-CCL24 axis in endothelial to mesenchymal transition process and pulmonary arterial hypertension in systemic sclerosis patients

  5. AASLD 2023: Serum proteomics reveals unique association of CCL24 with disease-related pathways and signatures in primary sclerosing cholangitis

  6. AASLD 2023: CM-101, a CCL24 neutralizing antibody, showed improvements in inflammatory, fibrotic, and metabolic pathways in patients with NASH: Proteomics analysis of a Phase 2a study

  7. EASL 2023-Phase 2a study of CM-101, a CCL24 Neutralizing Antibody, in Patients with Nonalcoholic Steatohepatitis: A Proof-of-Concept Study

  8. EASL 2023 - Serum Proteomics Reveals Association of CCL24 with Key Aspects of Primary Sclerosing Cholangitis

  9. EASL 2023 - Targeting CCL24 in Primary Sclerosing Cholangitis with CM-101: Rationale and Study Design

  10. EASL Biliary Conference 2023-Patient Proteomic Data and Mouse Model Reinforce the Proinflammatory Role of CCL24 in Cholestatic Disease

  11. EULAR 2023-CCL24 Serum Concentration Predicts Vascular and Fibrotic Complications in Systemic Sclerosis

  12. AASLD 2022 Liver Meeting - CCL24 Blockade Attenuates Biliary Inflammation by Interfering with Monocyte and Neutrophil Recruitment

  13. The Union Conference on Lung Health 2022--Treatment with CM-101 Reduced Inflammatory & Fibrotic Biomarkers in Patients with COVID-19-derived Lung Damage

  14. EASL 2022-Combination of Whole Liver Single Cell RNA Sequencing and Spatial Transcriptomics Reveals Specific Cell Sub-Populations and Pathways Regulated by CCL24

  15. ECM Congress 2022-CCL Inhibition by CM-101 Attenuates Extracellular Matrix and Fibrotic Biomarkers in Both Patients and Experimental Murine Models

  16. CCL24 overexpression resulting from bile duct injury induces an inflammatory-fibrotic vicious cycle in primary sclerosing cholangitis - AASLD 2021

  17. The peri-ductular CCL24 rich niche promotes bile duct fibrosis related liver damage in primary sclerosing cholangitis - EASL 2021

  18. CM-101 Demonstrates Reduction in Serum Fibrotic Biomarkers in a Phase 1b Clinical Trial - AASLD 2020

  19. CM-101 a Novel CCL24 Blocking Monoclonal Antibody Demonstrates Safety, Target Engagement and Long Half- Life in a Phase 1 Clinical Trial - AASLD 2020

  20. CCL24 modulates fibrosis development in Primary Sclerosing Cholangitis - EASL 2020

  21. CCL24 Blocking Monoclonal Antibody Reduces Cholangiocites Proliferation in Cholestasis Models – EASL 2019

  22. CCL24 Blocking Monoclonal Antibody Reduces Cholangiocites Proliferation in Cholestasis Models – AASLD 2019

  23. CCL24 -A novel target playing a significant role in Systemic Sclerosis (SSc)

  24. CCL24 Blocking Monoclonal Antibody Ameliorates Liver Injury in Models of Cholestasis – EASL 2018

  25. CM-101, CCL24 Blocking Antibody, Suppresses Hepatic Injury and Fibrosis in Models of NASH and Liver Fibrosis – AASLD 2018

  26. Expression of CCL24 and its Receptor CCR3 in Patients with Non-Alcoholic Fatty Liver Disease – EASL 2018