Chemomab Therapeutics Ltd. reported top-line results from its Phase 2a trial assessing CM-101, its first-in-class CCL24-neutralizing monoclonal antibody, in non-alcoholic steatohepatitis (NASH) patients. The trial met its primary endpoint of safety and tolerability, and CM-101 achieved reductions in secondary endpoints that include a range of liver fibrosis biomarkers and physiologic assessments measured at baseline and at week 20. The randomized, placebo-controlled trial enrolled 23 NASH patients with stage F1c, F2 and F3 disease who were randomized to receive either CM-101 or placebo.

Patients received eight doses of 5 mg/kg of CM-101 or placebo, administered by subcutaneous (SC) injection once every two weeks, for a treatment period of 16 weeks. This trial was primarily designed to assess the subcutaneous formulation of CM-101 and to evaluate the drug's impact on liver fibrosis biomarkers relevant to both NASH and the rare fibro- inflammatory conditions that represent the focus for the company, such as primary sclerosing cholangitis (PSC) and systemic sclerosis (SSc). Key findings of the CM-101 Phase 2a trial included the following.

CM-101 continues to appear safe and was well tolerated when administered subcutaneously. Most reported adverse events observed were mild, with one unrelated serious adverse event reported. No significant injection site reactions were observed and no anti-drug antibodies were detected.

CM-101 administered subcutaneously demonstrated favorable pharmacokinetics and target engagement profiles as expected; they were similar to what the company has previously reported. CM-101-treated patients showed greater improvements than the placebo group in a number of liver fibrosis-related biomarkers, including ProC-3, ProC-4, ProC-18, TIMP-1 and ELF. A majority of CM-101-treated patients showed improvements in more than one liver fibrosis- related biomarker—almost 60% of CM-101-treated patients responded in at least three biomarkers at week 20, compared to no patients in the placebo group.

CM-101-treated patients with higher CCL24 levels at baseline showed greater reductions in fibrosis-related biomarkers than patients with lower CCL24 levels. Patients with higher CCL24 at baseline were also more likely to be responders in multiple fibrosis-related biomarkers than patients with lower CCL24 levels, adding to the growing body of evidence validating the role of CCL24 in the pathophysiology of fibrotic liver disease. A higher proportion of patients in the CM-101-treated group showed improvement in a physiologic measure of liver stiffness as compared to placebo (reduction of at least one grade of fibrosis score as assessed by the non-invasive elastography method known as FibroScan®).

After completion of the study, the unblinded data showed that patients in the CM-101-treated group had higher baseline levels of fibrosis compared to placebo-treated patients. The impact of this difference on the results, if any, is unknown.