COUR Pharma's CNP-104 Shows Sustained Liver Function Improvements in Primary Biliary Cholangitis One-Year Study
Key Insights
CNP-104 demonstrated durable clinical effects one year after just two doses, achieving composite biochemical response criteria and showing sustained liver stiffness improvements versus placebo.
The investigational nanoparticle therapy targets the root cause of PBC (search) by inducing tolerance to pathogenic PDC-E2 (search) T cells that drive bile duct inflammation and progressive liver injury.
Results support CNP-104's potential as a novel therapeutic option for PBC (search) patients unresponsive to standard treatments, with favorable safety profile and no severe adverse events reported.
COUR Pharma (search) announced positive one-year results from its Phase 2a study of CNP-104 in primary biliary cholangitis (search) (PBC (search)), demonstrating sustained clinical benefits following just two doses of the investigational nanoparticle therapy administered one week apart. The results show durable improvements across key liver function markers and disease progression indicators in patients unresponsive to standard treatments.
Sustained Clinical Benefits After Single Treatment Course
The one-year data revealed that CNP-104 treated patients achieved separation from placebo on a composite biochemical response, defined as alkaline phosphatase (ALP) less than 1.67 times the upper level of normal with at least 15% reduction from baseline, and total bilirubin at or below the upper limit of normal. This composite endpoint represents an established measure of treatment response in PBC (search).
"CNP-104 demonstrated robust antigen-specific immune modulation consistent with restoration of immune tolerance in PBC (search), as shown in the previously announced day 120 analysis," said Dannielle Appelhans, Chief Executive Officer of COUR Pharma (search). "The one-year data confirms continued stabilization in liver stiffness measurements and validated prognostic risk scores, while newly demonstrating achievement of established composite biochemical response criteria at twelve months."
Additional sustained improvements included enhanced albumin levels, a marker of liver synthetic function, and continued statistically significant separation in liver stiffness versus placebo as measured by transient elastography (FibroScan®). Liver stiffness serves as a key independent marker of disease progression in PBC (search) patients.
Prognostic Risk Score Improvements
The study demonstrated improvements in the UK-PBC (search) prognostic risk score and its associated components, including ALP, bilirubin, alanine aminotransferase, albumin, and platelets. These markers collectively provide insight into disease progression and patient prognosis in PBC.
The Phase 2a first-in-human, double-blind, placebo-controlled clinical trial (NCT05104853) enrolled patients aged 18-75 who were unresponsive to treatment with ursodeoxycholic acid (UDCA) and/or obeticholic acid (OCA). The previously reported 120-day primary study period analysis had demonstrated modulation of the antigen-specific Th17 T-cell axis alongside the statistically significant clinical differentiation in liver stiffness measurements.
Favorable Safety Profile Maintained
CNP-104 maintained a favorable safety and tolerability profile through one year of follow-up. All drug-related adverse events were graded as mild or moderate (grade 1 or 2), with no drug-related severe adverse events (SAEs) reported during the extended follow-up period.
Targeting Disease Root Cause
CNP-104 is an investigational biodegradable nanoparticle encapsulating the E2 component of the mitochondrial pyruvate dehydrogenase complex (PDC-E2 (search)), a key autoantigen in PBC (search). The therapy aims to address the root cause of PBC by inducing tolerance to pathogenic PDC-E2 T cells that drive bile duct inflammation and progressive liver injury.
The drug has received both Orphan Drug Designation and Fast Track Designation from the United States Food and Drug Administration (FDA), reflecting the significant unmet medical need in PBC (search) treatment.
Addressing Significant Unmet Need
Primary biliary cholangitis (search) is a chronic, progressive autoimmune liver disease that primarily affects women between 40 and 60 years of age. The disease is characterized by loss of tolerance to mitochondrial antigens and T-lymphocyte-mediated destruction of small intrahepatic bile ducts. This immune-driven injury leads to cholestasis, progressive fibrosis, cirrhosis, and eventual liver failure, with some patients ultimately requiring liver transplantation. Symptoms such as fatigue and pruritus can significantly impair quality of life.
Development Strategy and Future Plans
Appelhans noted that the results "support the potential of CNP-104 as a novel therapeutic option of PBC (search) and inform our ongoing evaluation of the program's development strategy, including potential collaboration with a strategic partner."
COUR Pharma (search) plans to submit detailed one-year results from the Phase 2a study for presentation at future scientific conferences. The company's broader pipeline includes three proprietary clinical-stage programs targeting type 1 diabetes (search), myasthenia gravis (search), and primary biliary cholangitis (search), along with partnered programs with Takeda Pharmaceuticals (search) for celiac disease (search) and Genentech for an undisclosed indication.