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 potentially 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 and neutralizes CCL24, ameliorating its overexpression and blocking its harmful effects.

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, IPF and MASH.

CM-101 appears safe and well tolerated in healthy subjects and in fatty liver disease, MASH and PSC patients.

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

Publications

Machine learning identifies key proteins in primary sclerosing cholangitis progression and links high CCL24 to cirrhosis
Snir et al., Int. J. Mol. Sci. 2024, 25, 6042
Targeting CCL24 in inflammatory and fibrotic diseases: rationale and results from three CM-101 Phase 1 studies
Mor, et al., Drug Safety, June 2024
Serum CCL24 as a biomarker of fibrotic and vascular disease severity in systemic sclerosis
De Lorenzis, et al., Arthritis Care & Research, April 2024
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
CCL24 regulates biliary inflammation and fibrosis in primary sclerosing cholangitis
Mor et al. JCI Insight. 2023: 8(12): e162270
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
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
Blockade of CCL24 with a monoclonal antibody ameliorates experimental dermal and pulmonary fibrosis
Mor et al. Ann Rheum Dis 2019;78:1260–1268
Eotaxin-2 blockade ameliorates experimental autoimmune encephalomyelitis
Mausner-Fainberg et al. World J. Immunol. 2013 Mar; 3(1):7-14.
Anti eotaxin-2 antibodies attenuate the initiation and progression of experimental atherosclerosis
Mor et al. World J. Cardiovascular Dis. 2013; 3:339-46
Protective effect of eotaxin-2 inhibition in adjuvant-induced arthritis
Ablin et al. Clinical and Experimental Immunology. 2010; V161(2):276–83