Nebokitug (CM-101) Gets FDA Runway for PSC Approval

Christopher Bowlus, MD

Credit: UC Davis

Chemomab Therapeutics has announced the successful completion of an end-of-phase 2 meeting with the US Food and Drug Administration (FDA) and alignment with the FDA on the design of a single phase 3 registration study for nebokitug (CM-101) for the treatment of primary sclerosing cholangitis (PSC).¹

According to a February 19, 2025, press release from the company, the design of the phase 3 trial provides the first regulatory clarity on a streamlined path to potential full regulatory approval based on a single pivotal trial that does not require liver biopsy and uses a primary endpoint comprised of clinical events associated with disease progression in PSC.¹

“Until now, the pathway to drug approval in PSC has been problematic due to the lack of validated surrogate endpoints and clarity around primary efficacy endpoints for PSC registration trials. This has been a major hindrance to the development of effective therapies for PSC,” Christopher Bowlus, MD, the Lena Valente Professor and Chief of the Division of Gastroenterology and Hepatology at the University of California Davis School of Medicine, commented.¹ “The agreed composite endpoint approach for the nebokitug trial enhances our chances of efficiently and accurately identifying the potential clinical benefits of this promising new drug. Our patients with PSC are in urgent need of disease-modifying treatments, and I look forward to the launch of the nebokitug Phase 3 trial.”

A first-in-class dual-activity monoclonal antibody, nebokitug neutralizes CCL24, a soluble protein that helps drive the inflammatory and fibrotic pathways central to PSC and other fibro-inflammatory diseases. By inhibiting CCL24, nebokitug blocks both immune cell recruitment and fibroblast activation, interrupting the self-reinforcing fibro-inflammatory cycle resulting in fibrosis.¹

To date, Chemomab has reported positive results from 4 clinical trials of nebokitug, including the phase 2 SPRING trial in patients with PSC, an indication for which the drug has received FDA and EMA Orphan Drug and FDA Fast Track designations.2 SPRING achieved its primary safety endpoint and nebokitug-treated patients with moderate to advanced disease showed improvements across a range of disease-related secondary endpoints. A consistent pattern of greater improvement on the secondary endpoints was observed in the study arm receiving the higher 20 mg/kg dose of nebokitug.¹

“Key publications have shown that the reductions in PSC biomarkers in our nebokitug Phase 2 SPRING trial, especially the Enhanced Liver Fibrosis (ELF) and liver stiffness elastography measures, are associated with reductions in clinical events, increasing our confidence in the relevance of this approach for nebokitug and decreasing risk,” said Adi Mor, PhD, co-founder and Chief Executive Officer of Chemomab.¹

Of note, the open-label extension portion of the SPRING trial is ongoing, with results expected in the first quarter of 2025.¹

The latest phase 3 trial design focuses on a set of clinically meaningful events that occur over time as the disease progresses. According to the release from Chemomab, the trial’s primary endpoint will assess changes in the time-to-first-event of any one of a number of well-characterized PSC clinical events.¹

The trial will enroll approximately 350 patients with PSC to collect the requisite number of clinical events needed to demonstrate statistically significant changes between the treatment and placebo arms. It is estimated that in the absence of intervention, participants would require on average about 2 years to experience a clinically meaningful event. The trial will also capture data on key biomarkers such as elastography, ELF score, and cholangiography as additional indicators of clinical outcomes, which allows for possible inclusion of an interim analysis during the study.¹

“We are very pleased with the strong engagement and collaborative spirit expressed by FDA during our End-of-Phase 2 meeting. The planned study is an events-driven design that is similar to the approach used in many oncology registration trials. This design eliminates the need for invasive liver biopsies and costly, difficult-to-execute confirmatory studies,” said Chemomab Chief Medical Officer Matt Frankel, MD.¹ “The results of this trial could also support ex-U.S. global marketing authorizations. Furthermore, given the potentially disease-modifying activity demonstrated by nebokitug, the focus on disease progression-related events may allow us to achieve a broad label in PSC, in contrast to more limited symptom-related endpoints such as pruritus.”

References

1. ^{Chemomab. Chemomab Completes Successful End-of-Phase 2 Meeting and Aligns with FDA on Clear and Efficient Path to Potential Regulatory Approval for Nebokitug (CM-101) in Primary Sclerosing Cholangitis. February 19, 2025. Accessed February 19, 2025. https://investors.chemomab.com/2025-02-19-Chemomab-Completes-Successful-End-of-Phase-2-Meeting-and-Aligns-with-FDA-on-Clear-and-Efficient-Path-to-Potential-Regulatory-Approval-for-Nebokitug-CM-101-in-Primary-Sclerosing-Cholangitis}

2. ^{Chemomab. Chemomab Therapeutics Receives FDA Fast Track Designation for CM-101 for the Treatment of Primary Sclerosing Cholangitis. November 15, 2023. Accessed February 19, 2025. https://investors.chemomab.com/2023-11-15-Chemomab-Therapeutics-Receives-FDA-Fast-Track-Designation-for-CM-101-for-the-Treatment-of-Primary-Sclerosing-Cholangitis}