Chemomab Therapeutics Reports Positive Phase 2 Results for CM-101 in Treating Primary Sclerosing Cholangitis

Chemomab Therapeutics Ltd., a clinical-stage biotechnology firm, has announced promising topline results from its Phase 2 SPRING trial evaluating CM-101, a monoclonal antibody, in patients with primary sclerosing cholangitis (PSC). CM-101 demonstrated safety and tolerability, along with anti-fibrotic, anti-inflammatory, and anti-cholestatic effects, meeting both primary and secondary endpoints. This trial marks a significant milestone for Chemomab, providing clinical proof-of-concept for CM-101’s potential in treating PSC and other fibrotic diseases.

The SPRING trial assessed two doses of CM-101 (10 mg/kg and 20 mg/kg) in 76 PSC patients across the U.S., Europe, and Israel over a 15-week period. The double-blind, placebo-controlled study included patients who completed all doses and the final visit at Week 15. It also featured a subgroup analysis of those with moderate to advanced disease, indicated by a vibration-controlled transient elastography (VCTE) measure greater than 8.7 kPa. About half of the trial participants fell into this category.

Key results from the trial showed that CM-101 improved liver stiffness, a crucial marker of PSC progression, and recorded statistically significant improvements in pruritis scores, total bilirubin, liver function tests, and inflammation markers. Patients receiving the higher dose of 20 mg/kg demonstrated more pronounced improvements across these measures. CM-101 also showed a favorable safety profile with mild to moderate adverse events like fatigue, headache, and pruritis being equally distributed between placebo and treatment groups.

Liver stiffness, a well-validated biomarker, improved significantly in patients treated with CM-101 compared to placebo, particularly in those with moderate/advanced disease. This is the first instance of an investigational drug for PSC showing significant improvement in liver stiffness in a relatively short timeframe. Additionally, patients experienced reductions in pruritis scores on the 5-D Itch Scale starting as soon as six weeks after the initial dose, reaching statistical significance for the 10 mg/kg dose by Week 15.

Other notable findings include improvements in the Enhanced Liver Fibrosis (ELF) score, particularly for those on the higher dose, and reductions in PRO-C3 levels, a marker of fibrosis. Total bilirubin, an indicator of bile duct health, also showed dose-dependent improvements, supporting CM-101’s anti-cholestatic activity. Moreover, liver function tests, such as alkaline phosphatase (ALP) and other enzymes, showed notable decreases in patients receiving CM-101.

Inflammatory cytokines IL-6 and TGFβ1, which are downstream markers from the CCL24 target, were significantly reduced in patients treated with CM-101, especially those with moderate/advanced disease on the higher dose. This reduction underscores CM-101’s potential anti-inflammatory benefits.

Christopher Bowlus, MD, from the University of California Davis, highlighted the trial’s positive outcomes, especially the readiness of CM-101 to advance into late-stage trials and the progress in developing non-invasive biomarkers for PSC.

Chemomab is preparing for an End-of-Phase 2 meeting with the FDA to discuss these results and outline a Phase 3 trial for PSC. They plan to initiate this next phase in 2025 after receiving feedback from the FDA. The SPRING trial also includes an Open Label Extension (OLE) phase, allowing patients to continue receiving CM-101 for an additional 33 weeks. Over 90% of eligible participants opted for this extension, with results expected in early 2025.

Chemomab’s CM-101 has attracted interest for potential partnerships, and the company is exploring collaboration opportunities based on these positive results. CM-101 targets CCL24, which plays a critical role in promoting fibrosis and inflammation, positioning it as a promising candidate for treating various severe fibro-inflammatory diseases. To date, CM-101 has shown favorable safety and tolerability across multiple clinical trials.