Pipeline

Primary sclerosing cholangitis (PSC) is a chronic progressive cholestatic disease of the liver characterized by inflammation and strictures of the biliary tree inside and/or outside the liver. The pathological hallmarks of PSC include injury to the integrity of the biliary ducts, retention of bile acids and intrahepatic inflammation and progressive liver fibrosis.

Disease Prevalence and Comorbidities

PSC is a rare disease, with a prevalence of 1 out of 10,000, and is more prevalent in men than women (2:1 ratio). Peak age at onset of PSC is between 30 and 40 years. PSC patients frequently present with concomitant inflammatory bowel disease (up to 75%), and are at increased risk of developing hepatobiliary and colon cancers, which cause about half of all patient deaths. More than 50% of PSC patients need liver transplantation within 10–15 years of diagnosis, but in about 20% of these patients the disease reoccurs in the transplanted liver.

Current Treatment Options

There is no approved drug for treating PSC, therefore current treatment focuses on reductions of cholestasis and management of disease manifestations and complications (e.g., fatigue, pruritis).

CM-101: Scientific Findings

Chemomab established strong preclinical evidence that demonstrates the potent anti-cholestatic and anti-fibrotic effects of CM-101 in PSC. Specifically:

• The overexpression of CCL24 and its correlation with fibrotic biomarkers was demonstrated in liver tissue samples and sera of PSC patients
• CM-101 attenuated cholestasis and fibrosis in multiple PSC animal models

CM-101 was found to be safe in healthy volunteers and in patients with PSC, metabolic-associated fatty liver disease (MAFLD) and metabolic-associated steatohepatitis (MASH) across doses and multiple administrations.

CM-101 Phase 2a PSC SPRING trial

Chemomab is conducting a clinical study evaluating CM-101 in adult PSC patients. Topline data have been reported from the 15-Week placebo-controlled component of the SPRING trial.

CM-101 met the primary study endpoint, demonstrating a favorable safety profile over the 15-week treatment period. CM-101-treated patients with moderate/advanced disease showed improvements on a wide range of disease-related secondary endpoints, including assessments of changes from baseline relative to placebo at Week 15 in liver stiffness; in liver fibrosis biomarkers, including the Enhanced Liver Fibrosis (ELF) score and PRO-C3 levels; in total bilirubin and liver function tests; in pruritus (itch) and in markers of inflammation. Dose-dependent responses were observed for multiple disease-related biomarkers. A consistent pattern of greater improvement on the secondary endpoints was observed in the study arm receiving the higher 20 mg/kg dose of CM-101 and in the prespecified subgroup of PSC patients with moderate/advanced disease. The open label extension portion of the Phase 2 SPRING trial is continuing, with results expected to be reported in early 2025.

CM-101 has Orphan Drug designation in the U.S. and the European Union for PSC and received Fast Track designation from the U.S. FDA. for the treatment of PSC in adults.

To learn more about how CM-101 may interrupt the fibro-inflammatory vicious cycle believed to drive disease progression in PSC, see our Mechanism of Action (MOA) video at: MOA video

Chemomab conducted a Phase 2a trial assessing CM-101, in metabolic-associated steatohepatitis (MASH) patients.

The randomized, placebo-controlled trial enrolled 23 MASH patients 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, over16 weeks.

This trial was designed to assess a subcutaneous formulation of CM-101 and to evaluate the drug's impact on liver fibrosis biomarkers relevant to both MASH and the rare fibro-inflammatory conditions that represent the focus for the company.

The trial met its primary endpoint of safety and tolerability, and CM-101 achieved reductions in secondary endpoints that included a range of liver fibrosis biomarkers and physiologic assessments.

Proteomic analyses of patient data from this trial showed consistent and significant improvements in liver-related pathology pathways after treatment with CM-101.

Systemic sclerosis (SSc), also called scleroderma, is a rare, chronic autoimmune disease that is characterized by chronic inflammation, fibrosis of the skin and internal organs as well as vascular damage. SSc involves multiple internal body organs and the symptoms of the disease vary depending on the affected organs and extent of damage.

Disease Prevalence and Comorbidities

Peak age at onset of SSc is between 20 and 50 years, and it is more prevalent in women compared to men, at a 3:1 ratio. There are two forms of SSc:

• Limited cutaneous SSc, which is a slowly progressive disease with skin involvement restricted to the limbs and characterized by delayed-onset organ damage
• Diffuse cutaneous SSc, which is a more aggressive form of the disease that presents a widespread skin damage and risks rapid-onset organ damage, including effects on the kidneys, heart, lungs and gastrointestinal tract

Although SSc is considered rare, with an estimated prevalence of approximately 1 in 10,000, it has high morbidity and mortality. The prognosis varies significantly among people affected and is correlated to the extent of organ damage. Unfortunately, SSc has the highest mortality rate among the systemic rheumatic diseases with pulmonary damage being the main cause of death.

Current Treatment Options

One therapy is approved for slowing the rate of decline in pulmonary functions in patients with SSc associated with interstitial lung disease (SSc-ILD). Currently, there is no therapy approved for SSc beyond this manifestation. Current treatment is therefore directed at suppression of the immune system or management of specific disease manifestations (e.g., digital ulcers, pulmonary hypertension).

CM-101: Scientific Findings

Chemomab demonstrated the key role of CCL24 and the substantial anti-fibrotic effects of CM-101 in SSc, namely:

• In the sera and skin tissue samples of SSc patients, overexpression of CCL24 correlates with lung function deterioration
• CM-101 prevention and treatment normalizes fibrosis in experimental skin and lung animal models
• CM-101's direct anti-fibrotic and anti-inflammatory mechanism of action (MoA) was demonstrated in multiple ex-vivo and in-vitro studies

CM-101 was found to be safe and well tolerated in human across doses and throughout multiple administrations.

CM-101 has Orphan Drug designation for systemic sclerosis is the U.S. and European Union.

CM-101 Phase 2a SSc trial

Chemomab has an open U.S. IND to conduct a Phase 2 clinical trial of CM-101 in patients with systemic sclerosis. The trial is Phase 2-ready but patient enrollment has not yet been initiated.