Chemomab's CM-101 Shows Broad Activity and Disease-Modifying Potential in PSC at AASLD 2024

Chemomab Therapeutics Ltd., a clinical stage biotechnology company based in Tel Aviv, has presented promising results from its Phase 2 SPRING trial involving patients with primary sclerosing cholangitis (PSC). The findings were shared at the American Association for the Study of Liver Disease (AASLD) The Liver Meeting® 2024. The trial focused on assessing the efficacy of CM-101, a monoclonal antibody developed by Chemomab for treating fibro-inflammatory diseases. This antibody targets the soluble protein CCL24, known to promote fibrosis and inflammation.

Professor Christopher Bowlus, a prominent investigator in the study, detailed the trial data during an oral presentation. The study's design involved a double-blind, placebo-controlled method to evaluate the effects of two dosages of CM-101 (10 mg/kg and 20 mg/kg) administered every three weeks over a period of 15 weeks. A total of 76 patients participated in the trial. The analysis encompassed all patients who completed the treatment regimen and a prespecified subgroup of those with moderate to advanced disease, who are at a higher risk of rapid disease progression.

The primary endpoint of the SPRING trial was met, showing that CM-101 maintained a favorable safety profile throughout the 15-week treatment period. Adverse events reported were typically mild or moderate and appeared evenly distributed among the placebo and treated groups. Additionally, dose-dependent responses were observed across various secondary endpoints related to disease biomarkers. Notably, patients receiving the higher 20 mg/kg dose exhibited greater improvements.

Key secondary endpoint data revealed significant benefits in several areas:

1. **Liver Stiffness**: Measured using FibroScan®, liver stiffness showed improvement in all patients treated with CM-101 compared to the placebo group, with more pronounced benefits in those with moderate to advanced disease.

2. **ELF Scores**: Enhanced liver fibrosis (ELF) scores consistently improved over the treatment period in patients with substantial fibrosis treated with 20 mg/kg of CM-101. This group also showed significant reductions in the ELF components procollagen III N-terminal peptide (PIIINP) and tissue inhibitor of metalloproteinase 1 (TIMP-1).

3. **PRO-C3 Levels**: This serum biomarker, indicative of type III collagen synthesis, was reduced in all patients treated with CM-101, with greater reductions observed in those with advanced disease stages.

4. **Liver Biochemistry**: A consistent decline in liver biochemistry markers was noted among patients treated with the higher dose of CM-101, particularly in those with more severe disease.

5. **Bilirubin**: Total bilirubin levels improved in a dose-dependent manner in CM-101-treated patients, supporting the anti-cholestatic activity of the therapy.

6. **Pruritus**: Patients receiving CM-101 experienced reduced pruritus (itching) scores across all timepoints compared to the placebo group.

Dr. Bowlus concluded that CM-101 was not only well-tolerated but also demonstrated potential anti-inflammatory, anti-fibrotic, and anti-cholestatic effects in PSC patients. The data indicate that patients with moderate to advanced disease exhibited broad and consistent biomarker improvements linked to clinical outcomes. These findings advocate for the continued clinical development of CM-101 in PSC patients.

Matt Frankel, MD, Chief Medical Officer of Chemomab, emphasized the significance of CM-101's broad activity across multiple disease biomarkers, noting it as a first-of-its-kind therapy for PSC. He highlighted the importance of presenting these encouraging results at a major scientific forum and expressed anticipation for discussions with the FDA regarding a potential registrational trial set to begin by the end of the following year.

The open label extension of the Phase 2 SPRING trial, allowing all eligible patients to receive CM-101 for an additional 33 weeks, is ongoing, with results expected in early 2025. These advancements suggest hope for PSC patients in need of effective treatments.