CNP-104 demonstrated potential efficacy across multiple immunological and clinical measurements, supporting its continued development as the first disease-modifying treatment for Primary Biliary Cholangitis
CNP-104 was safe and well-tolerated, meeting all primary endpoints
Full data to be presented at a future scientific meeting
CHICAGO, Sept. 30, 2024 (GLOBE NEWSWIRE) -- COUR Pharmaceuticals, a clinical-stage biotechnology company developing first-in-class, disease-modifying therapies designed to induce antigen-specific tolerance for immune-mediated diseases, today announced positive 120-day data from its Phase 2a study evaluating CNP-104 as a potential treatment for patients with Primary Biliary Cholangitis (PBC), a chronic liver disease that is estimated to affect approximately 130,000 individuals in the U.S.
“These data highlight the potential of CNP-104 to be the first disease-modifying treatment for people living with PBC,” said Paul M. Peloso, M.D., Chief Medical Officer of COUR Pharmaceuticals. “In addition to safety and tolerability data supporting further studies, we observed multiple immunological and clinical measurements supporting mechanistic proof of concept for CNP-104. Additionally, we observed positive clinical endpoints such as a reduction in liver stiffness measured on Fibroscan in the active arms compared to placebo, with Fibroscan being a surrogate for reductions in fibrosis. These data suggest that CNP-104 has the potential to halt disease progression which would be a transformational advancement for people living with PBC. We look forward to presenting these encouraging data at an upcoming scientific meeting.”
Data Highlights:
- CNP-104 led to a slowing of disease progression in liver stiffness on Fibroscan, reaching a statistically significant decrease on day 120 in the active arms compared to placebo (p = 0.011)
- Study subjects in the placebo arm experienced a greater trending decrease in albumin levels compared with CNP-104 treated patients
- CNP-104 demonstrated a favorable T cell response in pathogenic CD4 T cell populations and tolerance inducing CD8 T cells
- Notably, Th17 T cells decreased in both number and percentage mean change, with statistically significant higher rates of response in the active arms versus placebo at day-120 (p = 0.0037)
- CNP-104 was safe and well tolerated, and all drug related adverse events (AEs) were mild (Grade 1 or 2) and no drug related severe adverse events (SAEs) were reported
The Phase 2a first-in-human, proof-of-concept, randomized clinical trial (NCT05104853) is designed to assess the safety, tolerability, pharmacodynamics, and efficacy of CNP-104 in patients aged 18-75, unresponsive to treatment with ursodeoxycholic acid (UDCA) and/or obeticholic acid (OCA). Participants received 4 mg/kg or 8 mg/kg of CNP-104 or placebo on Days 1 and 8 with all patients receiving two I.V. loading doses administered one week apart. Of the 41 subjects dosed, the final randomization ratio approximated 1:1:1 placebo to 4 mg/kg CNP-104 to 8 mg/kg CNP-104. This study report considers the 120-day primary study period while the 20-month long-term safety evaluation is ongoing.
Christopher Bowlus, M.D., the Lena Valente Professor and Chief, Division of Gastroenterology and Hepatology at UC Davis, and Principal Investigator for the study, added, “Despite the recent evolution of the PBC treatment landscape, there remains a significant unmet need for new treatments. Unlike CNP-104, current therapies do not address the root cause of the disease. While these data are early and from a small number of patients, they are incredibly promising and merit future investigation.”
Detailed results from the Phase 2a study of CNP-104 will be submitted for presentation at a future scientific conference.
About CNP-104:
CNP-104 is a biodegradable nanoparticle encapsulating the E2 component of the mitochondrial pyruvate dehydrogenase complex (PDC), a key autoantigen in PBC. CNP-104 aims to address the root cause of PBC by inducing tolerance to pathogenic activated PDC-E2 T-cells that drive inflammation in bile ducts, leading to improvement in clinical outcomes of liver health. In January 2022, CNP-104 received Fast Track Designation from the United States Food and Drug Administration (FDA), making it potentially eligible for Accelerated Approval and Priority Review, if relevant criteria are met.
About PBC:
Primary biliary cholangitis (PBC) is a chronic, life-threatening autoimmune disease of the liver that primarily affects women between 40 and 60 years old. PBC is one of the leading causes of liver transplant in women. People with PBC experience impaired bile flow (cholestasis) and accumulation of toxic bile acids in the liver, which can progress to fibrosis, cirrhosis and liver failure. Increasing fibrosis results in cirrhosis and eventual liver failure and the need for a transplant. Additional symptoms of PBC include fatigue and pruritus, which can have a significant impact on the quality of life for patients. While the exact cause of PBC is unknown, the presence of antimitochondrial antibodies (AMA) which target the E2 component of the mitochondrial pyruvate dehydrogenase complex (PDC), are highly associated with the development of the disease.
About COUR Pharmaceuticals:
COUR Pharmaceuticals is a clinical-stage biotechnology company developing therapies to treat patients with autoimmune diseases. COUR’s first-in-class therapies are based on our proprietary antigen-specific immune tolerance platform and are designed to reprogram the immune system to address the underlying root cause of immune-mediated diseases. Data from multiple clinical and preclinical programs have demonstrated the ability of COUR’s product candidates to induce antigen-specific immune tolerance and have the potential to treat a wide range of autoimmune diseases.
COUR is currently enrolling patients in a phase 1b/2a double-blind, placebo-controlled, multicenter clinical study in Myasthenia Gravis and developing a product candidate in Type 1 Diabetes in addition to having completed first-in-human studies in Celiac Disease (partnered with Takeda Pharmaceuticals), and Primary Biliary Cholangitis.
For more information, please visit www.courpharma.com
