Chemomab Announces Positive Phase Ib Results of its SPARK study testing CM-101 in NAFLD patients
- Category: Antibodies
- Published on Wednesday, 06 January 2021 11:46
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- CM-101, a first in class CCL24 blocking antibody, showed excellent safety and tolerability using both IV and SC administration
- Dose dependent target engagement was measured for both tested doses
- First human confirmation for CM-101 anti-fibrotic mechanism of action
TEL AVIV, Israel I January 5, 2021 I Chemomab Ltd., a clinical-stage biotech company focusing on discovery and development of innovative therapeutics for fibrosis-related diseases, today announces positive results of the phase Ib clinical trial of its lead compound CM-101 in nonalcoholic fatty liver disease (NAFLD) patients with normal liver function.
The SPARK study is a double-blind, placebo-controlled study designed to evaluate the safety, tolerability and pharmacokinetic (PK) profile of CM-101 in NAFLD patients with normal liver function. In addition, the study included exploratory evaluation of pharmacodynamic (PD) parameters. The study recruited two cohorts of eight patients randomized in a 3:1 ratio between CM-101 2.5 mg/kg given as IV infusion (cohort 1) or CM-101 5 mg/kg given as SC injection (Cohort 2) and placebo. Each patient received five CM-101 administrations, once every 3 weeks, and had a post treatment follow-up of 42 days.
CM-101 is a CCL24 blocking monoclonal antibody that demonstrates amelioration of fibrosis and inflammation in animal models of multiple indications and is being developed as a potential treatment for patients with fibrosis-related diseases, such as Primary Sclerosing Cholangitis (PSC) and Systemic Sclerosis (SSc).
In this study repeated CM-101 administrations were found to be safe and well- tolerated for both tested doses when given as IV infusion or SC injection. No safety signals or unexpected adverse events were observed for CM-101 and all reported adverse events were mild or moderate in intensity. No injection-related signs or symptoms were reported for both IV and SC administrations.
Five repeated CM-101 administrations showed a dose proportional PK profile. The CM-10 terminal half-life (T1/2) was similar to that seen in the phase I studies in healthy volunteers supporting long, once in 2-4, weeks administration. None of the patients developed anti-drug antibodies (ADA).
Exploratory analysis of multiple pharmacodynamic parameters, including measurement of collagen turnover and fibrotic biomarkers, such as Pro-C3, Pro-C4, C3M and TIMP1, showed beneficial effects. CM-101 treatment resulted in reduction of fibrotic and fibrogenesis markers compared to no change or slight elevation in the placebo treated group. These beneficial effects were accompanied by reduction in liver stiffness measured by FibroScan™ . This pharmacodynamic data will be used to support planning of the phase II studies.
"We are very pleased with the outcome of the SPARK study, and especially with the anti-fibrotic signal," said Dr. Adi Mor, CEO of Chemomab. "CM-101 was shown to be safe and well- tolerated, which taken together with the early indication of interference with fibrotic processes pave the way for testing CM-101 in phase II studies in fibrotic indications," Dr. Mor continued.
Prof. Rifat Safadi, Principal Investigator of the phase Ib study, Head of the Liver Unit, Gastroenterology and Liver Diseases, Division of Medicine at Hadassah Medical Center, Professor of Internal Medicine, Bowel, Liver Disease, and Metabolic Syndrome at Hebrew University in Israel, added: "In this phase Ib study, CM-101 administration, as IV infusions or SC injections, showed a very clean safety and tolerability profile. The early signal of CM-101 in fibrotic processes is very encouraging and will need to be further studied in patients with more active fibrotic processes."
Prof. Massimo Pinzani, Director of the UCL Institute for Liver & Digestive Health & the Sheila Sherlock Chair of Hepatology UK and world leader in liver fibrogenic disorders, commented: "I have been escorting Chemomab from early pre-clinical development and the completion of the CM-101 phase Ib study is a significant milestone for the company. The safety profile and pharmacodynamic effects shown in this Phase Ib study supports further testing of CM-101 in PSC patients in the ongoing phase IIa study in the UK and Israel."
CCL24 is a soluble protein found to be overexpressed in fibrotic tissues and plays a unique and pivotal role in promoting fibrosis and inflammation. CCL24 induces a dual effect that includes a direct activation of fibroblasts and recruitment of inflammatory cells to damaged tissues.
Chemomab's lead clinical candidate, CM-101, is a first in class monoclonal antibody targeting CCL24, a novel and differentiated fibrotic target. CM-101 has been shown to substantially attenuate fibrosis and inflammation across a wide range of in-vitro and in-vivo models, including experimental models of primary sclerosing cholangitis (PSC), systemic sclerosis (SSc), idiopathic pulmonary fibrosis (IPF) and NASH.
CM-101 has been shown to be safe and well-tolerated in phase I and Ib clinical studies in healthy volunteers and NAFLD patients and is currently being tested in a phase IIa study in PSC patients. A second phase II study in SSc is planned during 2021.
Chemomab is a clinical-stage biotech company focusing on the discovery and development of innovative therapeutics for fibrosis-related diseases with a high unmet need. Based on the unique and pivotal role of the soluble protein CCL24 in promoting fibrosis and inflammation, Chemomab developed CM-101, a monoclonal antibody designed to bind and block CCL24 activity. CM-101 has potential to treat multiple severe and life-threatening inflammatory and fibrotic diseases and is currently undergoing clinical development for the orphan diseases, Primary Sclerosing Cholangitis (PSC) and Systemic Sclerosis (SSc). In October 2020, Chemomab initiated the SPRING Study, its first phase 2 clinical trial evaluating the safety and efficacy of CM-101 in patients diagnosed with PSC. Chemomab is a privately held company supported by leading healthcare-focused investors, including OrbiMed and Peter Thiel. For more information on Chemomab, please visit www.chemomab.com.
Chemomab recently entered into a merger agreement with the Nasdaq listed company Anchiano Therapeutics Ltd. ("ANCN"), a biopharmaceutical company dedicated to the discovery, development, and commercialization of novel targeted therapies to treat cancer in areas of significant clinical need, in which the shareholders of Chemomab would become the majority holders of the combined company. The proposed merger will create a public company focused on advancing Chemomab's lead product, CM-101, for the treatment of fibrosis-related diseases with high unmet medical need.