Pipeline

Indication

Candidate

Discovery

Preclinical

Phase 1

Phase 2

Pivotal

IV — Intravenous

SC — Subcutaneous

Primary Sclerosing Cholangitis

Candidate

Discovery

Preclinical

Phase 1

Phase 2

Pivotal

CM-101 (IV)

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 compared to 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. More than 50% of PSC patients need liver transplantation within 10–15 years of diagnosis.

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 pre-clinical 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 and well tolerated in healthy volunteers and patients with nonalcoholic fatty liver disease (NAFLD) across doses and throughout multiple administrations.

Systemic Sclerosis

Candidate

Discovery

Preclinical

Phase 1

Phase 2

Pivotal

CM-101 (IV)

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.

Non-Alcoholic Steatohepatitis

Candidate

Discovery

Preclinical

Phase 1A

Phase 1B

Phase 2A

Phase 2B

Phase 3 / Pivotal

CM-101 (SC)

Non-Alcoholic Steatohepatitis (NASH) is the liver manifestation of a metabolic disorder, and is the severe form of non-alcoholic fatty liver disease (NAFLD). NASH is characterized by liver fat accumulation that result in liver inflammation. Over time the progressive liver inflammation causes fibrosis that can progress to liver cirrhosis, advanced liver failure that necessitates liver transplant.

Disease Prevalence and Comorbidities

Approximately one quarter of the general population suffers from NAFLD, which is characterized by liver fat accumulation (liver steatosis or fatty liver), in the absence of other causes such as alcohol consumption. Twenty percent (20%) of the NAFLD population develops NASH. The US prevalence of NASH was 17 million in 2016, and it is expected to increase by 56% to 27 million by 2030. Patients diagnosed with more severe NASH (F3-F4) are expected to increase from 3.5 million in 2016 to 8 million by 2030.

NASH as part of a metabolic disorder increases the risk for cardiovascular disease, which is the main cause of mortality in NASH patients. Moreover, NASH is predicted to become the leading indication for liver transplantation.

Current Treatment Options

While there is no approved treatment for NASH, lifestyle changes have been shown to affect its progression. These changes include losing weight, maintaining a healthy diet, or addressing underlying conditions such as hypothyroidism and diabetes. NASH treatment remains a high unmet need as no therapies are available to prevent or treat NASH, and lifestyle changes, although effective, are difficult to implement and maintain.

CM-101: Scientific Findings

Chemomab has developed a comprehensive preclinical package that confirms CCL24’s pivotal function and role as a single target in liver fibrosis. CCL24 neutralization by CM-101 showed potential in ameliorating fibrosis. The pre-clinical package includes:

  • The overexpression of CCL24 in NASH patient sera and liver tissue samples correlate with disease severity
  • CM-101 showed robust anti-fibrotic effects across multiple NASH and liver fibrosis animal models
  • In-vitro and ex-vivo studies demonstrated CM-101's direct anti-fibrotic and anti-inflammatory MoA using primary patient-derived cells

Chemomab has demonstrated that CM-101 was safe and well tolerated in healthy volunteers and NAFLD patients across doses and throughout multiple administrations. The interim analysis from a phase 1b NAFLD-patient clinical trial has demonstrated well-established target engagement, pharmacokinetics profile and improvements in fibrotic biomarkers and liver health parameters.