Chemomab Therapeutics (CCMB) Study Result summary

Study overview and design

• Phase II SPRING trial was a randomized, double-blind, placebo-controlled study evaluating CM-101 in 76 PSC patients across the US, Europe, and Israel, with dosing every three weeks for 15 weeks and an open-label extension for 33 weeks, with over 90% of eligible patients opting in.

• Patients received either 10 mg/kg or 20 mg/kg CM-101 or placebo; 56 received CM-101 and 20 received placebo.

• Patient demographics and baseline characteristics were similar across groups, including age, gender, liver function, and fibrosis markers.

• The study included patients with large duct PSC and elevated alkaline phosphatase, allowing stable IBD and UDCA use.

• Primary endpoint was safety/tolerability; secondary endpoints included liver stiffness, ELF score, fibrotic markers, pruritus, bilirubin, and liver enzymes.

Safety and tolerability

• CM-101 demonstrated a favorable safety and tolerability profile, meeting the primary endpoint, with most adverse events mild or moderate and similar between treatment and placebo groups.

• No deaths or serious treatment-related adverse events occurred; three SAEs were reported, none in the 20 mg/kg arm.

• Six patients discontinued due to adverse events, all resolving and none life-threatening.

• Treatment emergent adverse events were reported in 82% of CM-101 patients and 75% of placebo; discontinuation rates were low.

• Adverse events were consistent with PSC or mild in nature, with no concerning patterns.

Efficacy and biomarker outcomes

• CM-101 achieved primary and key secondary endpoints, showing statistically significant improvements in liver stiffness, ELF score, PRO-C3, pruritus, total bilirubin, and liver function tests, especially in moderate/advanced disease and at 20 mg/kg.

• Dose-dependent responses were observed, with greater improvements at 20 mg/kg and in patients with higher disease burden.

• Inflammatory cytokines IL-6 and TGF-β1 were significantly reduced in moderate/advanced patients at the higher dose.

• Pruritus improved significantly in both dose groups, with benefits seen as early as six weeks and reaching statistical significance at week 15.

• Pharmacokinetic profiles were favorable and dose-dependent, with broad and consistent biological activity, especially at 20 mg/kg.