Targeting CCL24 in Inflammatory and Fibrotic Diseases: Rationale and Results from Three CM-101 Phase 1 Studies

Area of Science:

• Immunology
• Hepatology
• Pharmacology

Background:

• Overexpression of C-C motif chemokine ligand 24 (CCL24) is implicated in inflammatory and fibrotic liver diseases such as MASLD and MASH.
• CM-101 is a humanized monoclonal antibody designed to neutralize CCL24, thereby reducing inflammation and fibrosis.
• Preclinical studies suggest CM-101's efficacy in mitigating inflammation and fibrosis.

Purpose of the Study:

• To evaluate the safety and tolerability of intravenous (IV) and subcutaneous (SC) CM-101 in healthy volunteers and patients with MASLD.
• To assess the pharmacokinetic profile of CM-101 following IV and SC administration.
• To investigate the effect of CM-101 on biomarkers of inflammation and fibrosis in MASLD patients.

Main Methods:

• Phase 1a studies involved healthy volunteers receiving single IV or SC doses of CM-101 (0.75-10.0 mg/kg) or placebo in a double-blind, randomized design.
• Phase 1b study included MASLD patients without MASH receiving IV or SC CM-101 (2.5-5.0 mg/kg) or placebo every three weeks for 12 weeks.
• Primary endpoints included safety, tolerability, and serum pharmacokinetic parameters.

Main Results:

• Adverse events were infrequent and generally mild to moderate across all studies.
• CM-101 exhibited a pharmacokinetic profile consistent with monoclonal antibodies, with a terminal half-life of approximately 19 days (IV) and 17 days (SC).
• In MASLD patients, CM-101 treatment correlated with reduced levels of serum inflammatory, fibrotic, and collagen turnover biomarkers.

Conclusions:

• CM-101 was well-tolerated in healthy volunteers and MASLD patients at doses up to 10.0 mg/kg.
• Both IV and SC formulations of CM-101 engaged their target, CCL24.
• These findings indicate the therapeutic potential of CM-101 for inflammatory and fibrotic liver diseases.