Chemomab's Nebokitug Shows Sustained Anti-Inflammatory Effects in 48-Week PSC Extension Study
核心洞察
Chemomab's Phase 2 SPRING trial open-label extension demonstrates that nebokitug maintained favorable safety and anti-inflammatory effects for up to 48 weeks in primary sclerosing cholangitis (搜索) patients.
The study reveals nebokitug's mechanism of action involves targeting macrophage-mediated pathways, with dose-dependent improvements in key biomarkers like ELF score and liver stiffness measurements.
Results from 50 patients support advancing nebokitug 20mg/kg to Phase 3 trials, with the drug showing particular efficacy in patients with moderate to advanced PSC (搜索) disease.
Chemomab Therapeutics (搜索) has announced compelling long-term data from its Phase 2 SPRING trial extension study, showing that nebokitug, a first-in-class monoclonal antibody targeting CCL24 (搜索), maintained its anti-inflammatory and anti-fibrotic effects for up to 48 weeks in patients with primary sclerosing cholangitis (搜索) (PSC (搜索)). The findings, presented at the American Association for the Study of Liver Disease (AASLD) The Liver Meeting® 2025, provide crucial insights into the drug's mechanism of action and support its advancement to Phase 3 trials.
Extended Safety and Efficacy Profile
The open-label extension study enrolled 50 of the 54 eligible patients who completed the initial 15-week double-blind portion of the SPRING trial. These patients received up to 33 additional weeks of nebokitug treatment, bringing the total treatment duration to 48 weeks. The extended study demonstrated that nebokitug appeared safe and well-tolerated throughout the treatment period, with sustained or continued improvements in inflammatory and fibrosis biomarkers.
"The positive data reported from the 15-week double-blind portion of the trial were durable for up to 48 weeks of treatment, showing that nebokitug continued to be well-tolerated, with broad and substantial improvements in the key biomarkers that are known to predict disease progression in PSC (搜索), including ELF score and liver stiffness," said Adi Mor, PhD, co-founder, Chief Executive Officer and Chief Scientific Officer of Chemomab.
The study showed particularly pronounced benefits in patients with moderate to advanced disease receiving the 20mg/kg dose of nebokitug, leading the authors to conclude that these results support the evaluation of nebokitug 20mg/kg in a Phase 3 trial in patients with PSC (搜索).
Mechanistic Insights into Macrophage Targeting
Two additional presentations provided new clinical data on nebokitug's mechanism of action, specifically its effects on macrophage-mediated pathways that are central to PSC (搜索) disease progression. The research revealed that sustained innate immune activation, prominently involving hepatic macrophages, is a key element of PSC pathogenesis. Elevated levels of macrophage-associated proteins have been observed in patients with PSC and correlate with poor clinical outcomes.
The study evaluated nebokitug's effect on macrophage-driven activity by assessing changes in key macrophage-related biomarkers known to be clinically meaningful through their association with clinical outcomes. Nebokitug treatment led to dose-dependent reductions in serum macrophage-related proteins compared to placebo-treated patients, predominantly in patients with moderate to advanced disease.
MST1 as a Key Biomarker
A particularly significant finding involved macrophage stimulating protein 1 (搜索) (MST1 (搜索)), which acts as a negative regulator of macrophage-associated inflammation. In patients with PSC (搜索), MST1 function is impaired due to a disease-associated genetic variant, and its expression in the liver is significantly lower compared to healthy individuals.
The SPRING study demonstrated that nebokitug induced a dose-dependent increase in MST1 (搜索), with no change observed in the placebo group. Notably, increases in MST1 were associated with greater reductions in liver stiffness measurements. A significant correlation was also observed between changes in MST1 and CCL24 (搜索), supporting MST1 as a downstream marker of CCL24 blockade.
The authors conclude that these results suggest MST1 (搜索) may serve as a biomarker of nebokitug activity and further support its anti-inflammatory mechanism of action. The analysis showed that changes in these biomarkers following treatment with nebokitug were associated with improvements in ELF score and liver stiffness measurements.
Clinical Significance and Future Development
The data suggest that nebokitug may halt or slow disease progression and improve clinical outcomes, which are the primary objectives of the upcoming Phase 3 study. All three presentations at AASLD have been designated as Posters of Distinction, highlighting the scientific significance of the findings.
Nebokitug is a first-in-class dual activity monoclonal antibody that neutralizes CCL24 (搜索), a soluble protein that plays a unique role in promoting fibrosis and inflammation. The drug has received FDA and EMA Orphan Drug and FDA Fast Track designations for the treatment of PSC (搜索), a devastating disease with no currently approved therapies.
Based on the positive data from the Phase 2 SPRING trial, Chemomab is preparing for potential initiation of a nebokitug Phase 3 trial in patients with PSC (搜索). The Phase 3 design calls for a single pivotal trial based on a clinical event primary endpoint that provides a clear and streamlined pathway to potential full regulatory approval.
The company has reported positive results from five clinical trials of nebokitug across multiple fibro-inflammatory diseases (搜索), demonstrating the drug's potential to treat severe and life-threatening conditions with high unmet medical need.