─Treatment with CM-101 Improves Additional Biomarkers of Fibrosis and Inflammation,
`Reinforcing and Extending Initial Study Results─
─Provides New Insights into CM-101 Activity in NASH Patients at Greater Risk of Progressive Disease, Providing Further Support for CM-101’s Direct Anti-inflammatory and Anti-fibrotic Dual Mode of Action─
─Demonstrates Improvements in Key Biomarkers Associated with Other Fibrotic Liver Diseases
Including Primary Sclerosing Cholangitis─
TEL AVIV, Israel, June 21, 2023 /PRNewswire/ — Chemomab Therapeutics Ltd. (Nasdaq: CMMB), (Chemomab), a clinical stage biotechnology company developing innovative therapeutics for fibro-inflammatory diseases with high unmet need, today reported topline results from secondary analyses of its Phase 2a liver fibrosis trial assessing CM-101, its first-in-class CCL24-neutralizing antibody, in patients with non-alcoholic steatohepatitis (NASH). The results were included in a late-breaking poster presentation at the 2023 EASL Congress in Vienna, Austria.1
Overall, the data showed improvements across an additional set of inflammatory and fibrotic biomarkers that are consistent with the positive clinical results Chemomab released in January. Additionally, in NASH patients at greater risk of disease progression, CM-101 treatment resulted in a greater biomarker response than in NASH patients with lower risk disease or in placebo-treated patients.
Adi Mor, PhD, Chemomab co-founder, CEO and CSO, commented, “These additional analyses of our liver fibrosis data in NASH patients are very encouraging. They supplement and extend our initial data results, showing a consistent pattern of improvement in CM-101-treated patients in biomarkers associated with fibrogenesis and inflammation. We are especially pleased to see that CM-101 treated-patients with higher FAST scores—those at greater risk of progressive disease—tended to demonstrate greater biomarker improvements than those with lower FAST scores. Additionally, we consider these data to be highly relevant to our ongoing CM-101 Phase 2 trial in primary sclerosing cholangitis (PSC), demonstrating improvements in biomarkers that are also associated with the inflammation and fibrogenesis found in PSC patients. Notably, our PSC trial involves the evaluation of significantly higher doses of CM-101, with patient dose cohorts of 10mg/kg and 20mg/kg administered intravenously, compared to the liver fibrosis study in NASH patients, which used a subcutaneous dose of 5mg/kg.”
The new analyses assessed additional biomarkers and also used the FibroScan-AST (FAST) score to categorize study patients based on progressive disease risk, thereby enabling the evaluation of CM-101 activity in the main target population of patients with more active disease.2 FAST is a validated score composed of non-invasive FibroScan® and AST measurements that is used to identify patients with a high risk of NASH progression.3 The results showed that:
- FAST scores were improved in a higher proportion of CM-101-treated patients than in placebo patients.
- CM-101-treated patients with higher FAST scores demonstrated greater improvements in key fibro-inflammatory biomarkers, such as Pro-C3, than patients with lower FAST scores or placebo patients.
- CM-101-treated patients with higher FAST scores showed improvements in several fibro-inflammatory biomarkers generally comparable to those achieved in several recent successful NASH clinical trials.
In these secondary analyses, CM-101-treated patients showed improvements in an additional set of biomarkers associated with active fibrosis and inflammation:
- FIB-4, an index for determining NASH status that includes age, platelet count, AST and ALT levels, was improved in CM-101-treated patients vs. placebo patients.
- AST/ALT ratio, a liver enzyme ratio, was improved in CM-101-treated patients vs. placebo patients.
- Neutrophil-to-Lymphocyte Ratio (NLR), an indicator of inflammation, was improved in CM-101-treated patients vs. placebo patients, and NLR was further improved in groups with higher FAST scores.
- PRO-C3, which captures active fibrogenesis and correlates with fibrotic disease severity, was improved in CM-101-treated patients vs. placebo patients and was further improved in groups with higher FAST scores. As an overall indicator of fibrogenesis and fibrotic disease, PRO-C3 is also considered a “bridge” to PSC and other anti-fibrotic indications.
Scott L. Friedman, MD, Dean for Therapeutic Discovery and Chief of the Division of Liver Diseases at the Icahn School of Medicine at Mount Sinai in New York City, is an expert on the fibrosis associated with chronic liver disease and a co-author of the EASL poster. Dr. Friedman noted, “It is encouraging that consistent positive improvements are seen across a range of fibro-inflammatory biomarkers in both CM-101 Phase 2a study analyses. The greater improvement in biomarkers in the higher FAST score-enriched subgroup provides further evidence of CM-101’s potential to have a positive impact on fibrotic diseases such as NASH and PSC, whose pathophysiology may be associated with the dual fibro-inflammatory mechanism that CM-101 is intended to address.”
In January, the company reported that the Phase 2a liver fibrosis trial met its primary endpoint of safety and tolerability and that CM-101 achieved reductions in secondary endpoints that included a range of liver fibrosis biomarkers and physiologic assessments. The EASL poster also summarized these results, including:
- CM-101 treatment demonstrated a favorable PK-target engagement profile.
- CM-101 treatment was associated with improvements in multiple fibrosis biomarkers and with a reduction in FibroScan liver stiffness stage.
- CM-101 treatment was associated with improvements in more than one liver fibrosis-related biomarker—almost 60% of CM-101 patients responded in at least three biomarkers, compared to no placebo patients.
- Higher levels at baseline of CM-101’s target—the soluble chemokine CCL24—in CM-101-treated patients were associated with greater reductions in fibrosis-related biomarkers and a greater likelihood of being a multiple biomarker responder.