SPRING: CM-101, A CCL24-Neutralizing Antibody, Impresses in Phase 2 PSC Trial

Adi Mor, PhD

Credit: Chemomab

Chemomab Therapeutics has announced positive topline results from the phase 2 SPRING trial assessing CM-101, a first-in-class CCL24-neutralizing antibody, in patients with primary sclerosing cholangitis (PSC).¹

Results showed treatment with CM-101 achieved the trial’s primary endpoint of safety and tolerability and demonstrated anti-fibrotic, anti-inflammatory, and anti-cholestatic effects across a range of disease-related secondary efficacy endpoints, making it the first investigational drug being developed for PSC to exhibit broad, clinically relevant effects on all 3 components of the disease.¹

“We are thrilled to report the positive results of the Phase 2 SPRING trial that represent a major milestone for Chemomab and establish clear clinical proof-of-concept for CM-101 in PSC and potentially other fibrotic diseases,” Adi Mor, PhD, co-founder, chief executive officer and chief scientific officer of Chemomab, said in a press release.¹ “We believe these results provide strong support for advancing CM-101 to a Phase 3 PSC trial, which we are planning to initiate in 2025 after our interactions with the FDA later this year.”

A first-in-class monoclonal antibody, CM-101 neutralizes the soluble protein CCL24, which has been shown to drive the inflammatory and fibrotic pathways central to many fibro-inflammatory diseases and is thought to be associated with key pathways underlying PSC pathophysiology. On November 15, 2023, the US Food and Drug Administration granted CM-101 Fast Track designation for the treatment of adult patients with PSC.^1,2

A double-blind, placebo-controlled, phase 2 study, SPRING assessed the safety and tolerability of 2 doses of CM-101 (10 mg/kg and 20 mg/kg) administered via intravenous infusion every 3 weeks for 15 weeks. A total of 76 patients from the US, Europe, and Israel were treated in the trial.¹

As described in the press release, CM-101 demonstrated a favorable safety profile and was generally well-tolerated over the 15-week treatment period, also exhibiting favorable and dose-dependent pharmacokinetic profiles. Adverse events, which most commonly included fatigue, headache, and pruritis, were generally mild/moderate and distributed similarly between the placebo and CM-101 arms.¹

Patients with moderate/advanced disease treated with CM-101 experienced improvements across a wide range of disease-related secondary endpoints, including liver stiffness; in liver fibrosis biomarkers, including the Enhanced Liver Fibrosis (ELF) score and PRO-C3 levels; total bilirubin and liver function tests; pruritis; markers of inflammation from baseline relative to placebo at week 15. Of note, these results make SPRING the first PSC trial to show a statistically significant reduction in liver stiffness after 15 weeks of treatment, and CM-101 is among the first investigational drugs to show a reduction in total bilirubin as well as reductions in pruritis. According to the release, dose-dependent responses were observed for multiple disease-related biomarkers, with a consistent pattern of greater improvement on the secondary endpoints observed in the study arm receiving 20 mg/kg of CM-101 and in the prespecified subgroup of PSC patients with moderate/advanced disease.¹

The SPRING trial includes an open-label extension available to study participants who completed the double-blind portion of the study, more than 90% of whom elected to join the extension and receive infusions of either 10 mg/kg or 20 mg/kg of CM-101 every 3 weeks for an additional 33 weeks. According to the release from Chemomad, topline treatment results from this portion of the study, which will include patients with up to 48 weeks of exposure to CM-101, are expected to be available in the first quarter of 2025.¹

Additionally, Chemomab is preparing for an end-of-phase 2 meeting with the FDA to discuss the SPRING trial results and the design of a proposed phase 3 PSC trial for accelerated approval, with both discussions anticipated to be completed by the end of 2024 and official written feedback from the FDA expected in the first quarter of 2025.¹

“These positive trial results come at an opportune time, with promising therapies like CM-101 ready to advance into late-stage trials and recent progress to develop non-invasive biomarkers as registration endpoints in PSC that will meet FDA standards,” said 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.¹ “This is welcome news for the many patients with PSC desperate for new therapeutic options to combat this challenging disease.”

References

1. ^{Chemomab Therapeutics. Chemomab Therapeutics Announces Positive Phase 2 Trial Results: CM-101 Achieves Primary and Secondary Endpoints Demonstrating Anti-Fibrotic, Anti-Inflammatory and Anti-Cholestatic Effects in Patients with Primary Sclerosing Cholangitis. July 25, 2024. Accessed July 25, 2024. https://investors.chemomab.com/2024-07-25-Chemomab-Therapeutics-Announces-Positive-Phase-2-Trial-Results-CM-101-Achieves-Primary-and-Secondary-Endpoints-Demonstrating-Anti-Fibrotic,-Anti-Inflammatory-and-Anti-Cholestatic-Effects-in-Patients-with-Primary-Sclerosing-Cholangitis}
2. ^{Chemomab Therapeutics. Chemomab Therapeutics Receives FDA Fast Track Designation for CM-101 for the Treatment of Primary Sclerosing Cholangitis. November 15, 2023. Accessed July 25, 2024. https://investors.chemomab.com/2023-11-15-Chemomab-Therapeutics-Receives-FDA-Fast-Track-Designation-for-CM-101-for-the-Treatment-of-Primary-Sclerosing-Cholangitis}