More studies support use of CM-101 antibody therapy now in PSC trial

Data from trials, AI-based study show treatment's potential: Chemomab

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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High levels of CCL24, the protein targeted by Chemomab Therapeutics’ investigational antibody-based therapy CM-101, are associated with biological pathways contributing to the progression of primary sclerosing cholangitis (PSC).

That’s according to a study that used an artificial intelligence tool to identify a PSC protein signature based on patient samples.

These findings “add to the large body of data showing that CCL24 is a major driver of PSC disease progression and severity,” Adi Mor, PhD, Chemomab’s co-founder, CEO, and chief scientific officer, said in a company press release.

“They also confirm the importance of both fibrotic [scarring] and inflammation/immune-related pathways in PSC, highlighting the relevance of the dual anti-fibrotic and anti-inflammatory activity of CM-101,” Mor added.

Moreover, another study, reporting data from three Phase 1 trials, showed that CM-101 was generally well tolerated and effectively targeted CCL24 in healthy adults, while also reducing liver inflammation and scarring in people with a type of fatty liver disease.

CM-101 in now being tested in adults with PSC affecting the large bile ducts as part of a Phase 2a clinical trial called SPRING (NCT04595825).

“We look forward to our CM-101 PSC Phase 2 topline data readout in the coming weeks, which has the potential to provide the first significant clinical proof-of-concept of CM-101’s therapeutic activity in this lethal disease with no [U.S. Food and Drug Administration] approved therapies,” Mor said.

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PSC is a rare chronic liver disease characterized by cholangitis, or inflammation in the series of tubes that carry the digestive fluid bile from the liver to the intestines. Those tubes are known as the bile ducts.

Over time, bile duct inflammation and fibrosis can cause impaired bile flow, or cholestasis. This damages the liver and may eventually lead to more serious liver-related complications. However, the disease remains without any approved treatments.

CM-101 is an antibody designed to neutralize CCL24, a protein found to play a role in driving inflammation and scarring.

Chemomab has demonstrated that blood CCL24 levels are increased in PSC patients, and are associated with disease-associated pathways and inflammatory markers. In a mouse model of cholestasis, treatment with CM-101 eased liver inflammation and fibrosis.

The therapy was granted both orphan drug and fast track designations for PSC by U.S. regulators, as well as orphan drug status in the European Union. These designations are expected to speed CM-101’s clinical development and regulatory review.

In one of the recent publications, Chemomab researchers conducted protein analyses of blood samples from PSC patients and healthy people to identify a PSC protein signature and explore the role of CCL24 in this condition.

Specifically, the scientists used machine learning — a form of artificial intelligence, or AI, that uses algorithms to analyze data, learn from its analyses, and then make a prediction about something.

The study detailing their findings, titled “Machine Learning Identifies Key Proteins in Primary Sclerosing Cholangitis Progression and Links High CCL24 to Cirrhosis,” was published in the International Journal of Molecular Sciences.

The results showed that proteins most associated with PSC were commonly involved in inflammatory and fibrotic pathways, and correlated with clinical liver fibrosis scores.

Moreover, PSC-related biological pathways were associated with higher blood CCL24 levels. Patients with cirrhosis, or irreversible liver fibrosis and damage, had higher CCL24 levels than those without it.

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Top-line results of CM-101 Phase 2b study expected soon

In the other study, “Targeting CCL24 in Inflammatory and Fibrotic Diseases: Rationale and Results from Three CM-101 Phase 1 Studies,” which was published in Drug Safety, scientists summarized the findings from three Chemomab-sponsored Phase 1 studies that tested CM-101 against a placebo.

Two of the trials evaluated the safety and pharmacological properties of CM-101 in healthy adults. In these trials, the therapy was administered either via infusion into the bloodstream (intravenously; NCT06025851) or through under-the-skin injections (subcutaneously; NCT06037577).

Another Phase 1b study (NCT06044467) tested both intravenous and subcutaneous CM-101 in 16 people with metabolic dysfunction-associated steatotic liver disease (MASLD), a type of fatty liver disease that’s marked by liver fat accumulation and inflammation that can progress to liver scarring.

Across the studies, doses ranging from 0.75 to 10.0 mg/kg were generally well tolerated, with most adverse events being mild or moderate in severity. CM-101 was also shown to effectively bind and neutralize CCL24.

In MASLD patients, CM-101 led to reductions in blood levels of inflammation and fibrosis markers relative to the placebo.

The ongoing Phase 2a SPRING trial of CM-101 involves 68 adults with PSC. Each was randomly assigned to receive either 10 or 20 mg/kg CM-101, or a placebo, given intravenously once every three weeks for about four months. This part will be followed by an open-label extension phase in which all participants will receive CM-101 for approximately eight months.

The trial’s main goal is to evaluate safety, with secondary goals including measures of CM-101’s pharmacological properties and effects on liver health.

According to the company, top-line data from the trial is expected soon.

Chemomab also is testing CM-101 as a possible treatment for metabolic dysfunction-associated steatohepatitis, a severe form of MASLD, and systemic sclerosis, a chronic autoimmune disease. Both are also characterized by inflammation and scar tissue buildup.