About Nebokitug (CM-101)
Nebokitug is a first-in-class dual activity monoclonal antibody that neutralizes CCL24, a soluble protein that helps drive the inflammatory and fibrotic pathways central to primary sclerosing cholangitis and other fibro-inflammatory diseases. By inhibiting CCL24, nebokitug blocks immune cell recruitment and fibroblast activation, thereby interrupting the self-reinforcing cycle that results in fibrosis. In clinical and preclinical studies, nebokitug has been shown to have a favorable safety profile, with the potential to treat multiple severe and life-threatening fibro-inflammatory diseases. Chemomab has reported positive results from five clinical trials of nebokitug, including positive nebokitug safety studies in healthy volunteers and patients with MAFLD, MASH, acute lung injury and PSC. The Phase 2 SPRING study achieved the primary safety endpoint and nebokitug-treated patients with moderate/advanced disease showed improvements on a wide range of disease-related secondary endpoints after 15-weeks and 48-weeks of treatment. The nebokitug systemic sclerosis (SSc) program has an open U.S. IND. Nebokitug has received FDA and EMA Orphan Drug designations for the treatment of PSC and SSc and FDA Fast Track status for the treatment of PSC in adults.
Nebokitug Phase 2 SPRING Trial Results in Patients with Primary Sclerosing Cholangitis
Summary of SPRING Trial 15-Week Results
In the 15-week double-blind, placebo-controlled portion of the SPRING trial, treatment with nebokitug achieved its primary endpoint of safety and tolerability and demonstrated broad, clinically-relevant anti-fibrotic, anti-inflammatory and anti-cholestatic effects across a broad range of disease-related secondary efficacy endpoints, including a statistically significant improvement in liver stiffness, a key PSC disease marker.
The SPRING study assessed two doses of nebokitug (10 mg/kg and 20 mg/kg) administered to PSC patients every three weeks over 15 weeks. A total of 76 patients were treated in the trial. The study analysis included assessments of all study completers, as well as a prespecified subgroup analysis of moderate/advanced patients with a higher risk of more rapidly progressing disease. Approximately half of the SPRING study patients were classified as having moderate/advanced disease, which is similar to the overall PSC patient population.
Nebokitug met the primary study endpoint, demonstrating a favorable safety profile over the 15-week treatment period. Nebokitug-treated patients with moderate/advanced disease showed improvements on a wide range of disease-related secondary endpoints, including assessments of changes from baseline relative to placebo at Week 15 in liver stiffness (transient elastography); in liver fibrosis biomarkers, including the Enhanced Liver Fibrosis (ELF) score and PRO-C3 levels; in total bilirubin and liver function tests; in pruritis (itch) and in markers of inflammation. Dose-dependent responses were observed for multiple disease-related biomarkers. A consistent pattern of greater improvement on the secondary endpoints was observed in the study arm receiving 20 mg/kg of nebokitug and in the prespecified subgroup of PSC patients with moderate/advanced disease.
Summary of SPRING Trial 48-Week Results
The Open Label extension (OLE) portion of the SPRING trial was open to all eligible study participants, who received either 10 or 20 mg/kg of nebokitug for an additional 33 weeks, for up to 48 weeks of treatment. The results confirmed that the drug was safe and well-tolerated and resulted in positive effects, including continued improvements in key liver biomarkers such as the ELF score, the fibrosis-related components of ELF and PRO-C3. Liver stiffness scores were substantially lower in the nebokitug-treated patients with moderate/advanced disease compared to matching historical controls. Cholestasis-related markers stabilized over 48 weeks of treatment and total serum bile acids were reduced. OLE patients with moderate/advanced disease treated with nebokitug for 48 weeks showed a significantly lower number of clinical events (4.8%) compared to historical controls (25.8%).