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Chicago-based COUR Pharma announced one-year results from its Phase IIa study of CNP-104 in primary biliary cholangitis (PBC), reporting that two doses of the antigen-specific nanoparticle therapy produced durable improvements in cholestatic and fibrosis-related endpoints relative to placebo. The data provide continued support for a mechanistic approach — antigen-specific immune tolerance induction — that has no approved precedent in PBC and that COUR Pharma is pursuing without a large pharma partner for this indication. Trial specifics The Phase IIa first-in-human randomized study (NCT05104853) is a double-blind, placebo-controlled trial enrolling adults aged 18–75 with PBC who had an inadequate response to ursodeoxycholic acid and/or obeticholic acid. Patients received two intravenous doses of CNP-104 administered one week apart, followed by long-term observation extending to 20 months. The primary study period covered the first 120 days, with one-year data now reported as a prespecified follow-up analysis. At 12 months, COUR reported separation from placebo on a composite biochemical response endpoint defined as serum alkaline phosphatase below 1.67× the upper limit of normal, at least a 15% reduction from baseline, and total bilirubin at or below the upper limit of normal. The company also reported statistically significant separation from placebo in liver stiffness measured by transient elastography, improvements in albumin as a marker of hepatic synthetic function, and improvement in the UK-PBC prognostic risk score. All drug-related adverse events were graded mild or moderate, with no drug-related serious adverse events through one year. Exact numerical values for endpoints were not disclosed; the company said full results will be submitted for presentation at a future scientific conference. CEO Dannielle Appelhans said the data “support the potential of CNP-104 as a novel therapeutic option” and “inform our ongoing evaluation of the program’s development strategy, including potential collaboration with a strategic partner”. CNP-104 holds both Orphan Drug Designation and Fast Track Designation from the US FDA. No timeline for a Phase III study or regulatory filing has been disclosed. Research context CNP-104 is a biodegradable PLGA nanoparticle encapsulating PDC-E2, the E2 subunit of the mitochondrial pyruvate dehydrogenase complex. In PBC, loss of immune tolerance to PDC-E2 drives T-cell-mediated destruction of intrahepatic bile ducts, leading to cholestasis, fibrosis, and eventual liver failure. By delivering PDC-E2 in a tolerogenic context to antigen-presenting cells, CNP-104 aims to selectively silence the pathogenic autoimmune response without broad immunosuppression. This mechanism is distinct from all currently approved PBC therapies, which primarily target bile acid metabolism or downstream inflammatory pathways rather than the underlying autoimmune trigger. PBC predominantly affects women aged 40–60. First-line therapy remains ursodeoxycholic acid, to which roughly 40% of patients respond inadequately. Two second-line agents have received US FDA approval: obeticholic acid (Ocaliva, Intercept/Advanz, approved in 2016) and seladelpar (Livdelzi, originally developed by CymaBay Therapeutics and approved in 2024; now part of Gilead Sciences following its acquisition of CymaBay). Both act on bile acid or PPAR signaling pathways rather than directly addressing the autoimmune driver of the disease. Additional therapies in development include Zydus Therapeutics’ saroglitazar magnesium, a dual PPARα/γ agonist approved for PBC in India and currently being evaluated in Phase II/III and Phase III studies for broader regulatory markets. No other antigen-specific immune tolerance therapy for PBC is currently in clinical development. COUR Pharma’s nanoparticle platform also underpins two additional clinical programs — CNP-101 for celiac disease, partnered with Takeda, and a program in type 1 diabetes currently enrolling a Phase Ib/IIa study — as well as an undisclosed collaboration with Genentech.

CNP-104 improved key cholestasis endpoints at one year, including a composite serum alkaline phosphatase (ALP) and bilirubin biochemical response Durable effects observed across liver stiffness, prognostic risk markers, and liver function following only two doses of CNP-104 administered one week apart Full one-year dataset to be presented at future scientific meetings CHICAGO, March 03, 2026 (GLOBE NEWSWIRE) -- COUR Pharma, a clinical-stage biotechnology company developing first-in-class, antigen-specific immune tolerance therapies for autoimmune diseases, today announced positive one-year results from its Phase 2a study evaluating CNP-104 as a potential treatment for patients with Primary Biliary Cholangitis (PBC). “CNP-104 demonstrated robust antigen-specific immune modulation consistent with restoration of immune tolerance in PBC, as shown in the previously announced day 120 analysis,” said Dannielle Appelhans, Chief Executive Officer of COUR Pharma. “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. Together, these results spanning both positive fibrotic and cholestatic biomarkers support the potential of CNP-104 as a novel therapeutic option of PBC and inform our ongoing evaluation of the program’s development strategy, including potential collaboration with a strategic partner.” Following two loading doses of CNP-104, one-year findings show durable clinical effects including: Separation of CNP-104 treated patients from placebo on a composite biochemical response (defined as ALP <1.67× upper level of normal (ULN), ≥15% reduction from baseline, and total bilirubin ≤ ULN) Improvements in albumin, a marker of liver synthetic function Sustained statistically significant separation of liver stiffness versus placebo, a key independent marker of disease progression 1 Improvement in the UK-PBC prognostic risk score and associated components (ALP, bilirubin, alanine aminotransferase, albumin, platelets) Favorable safety and tolerability pro one year of follow-up, with all drug related adverse events graded as mild or moderate (grade 1 or 2), with no drug related severe adverse events (SAEs) reported The Phase 2a first-in-human, double-blind, placebo controlled clinical trial ( NCT05104853 ) was designed to assess the safety, tolerability, pharmacodynamics, and efficacy of two doses of CNP-104 administered one week apart in patients aged 18-75 who were unresponsive to treatment with ursodeoxycholic acid (UDCA) and/or obeticholic acid (OCA) 2 . The previously reported 120-day primary study period analysis demonstrated modulation of the antigen specific Th17 T-cell axis, together with statistically significant clinical differentiation in liver stiffness measurement assessed by transient elastography (FibroScan ® ). Detailed one-year 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 an investigational biodegradable nanoparticle encapsulating the E2 component of the mitochondrial pyruvate dehydrogenase complex (PDC-E2), a key autoantigen in PBC. CNP-104 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. CNP-104 has been granted Orphan Drug Designation as well as Fast Track Designation by the United States Food and Drug Administration (FDA). About PBC Primary biliary cholangitis (PBC), formerly known as primary biliary cirrhosis, 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. About COUR Pharma COUR Pharma is a clinical-stage biotechnology company developing first-in-class therapies to treat patients with autoimmune diseases. COUR’s 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 has three proprietary clinical-stage programs - type 1 diabetes, myasthenia gravis and primary biliary cholangitis, and is currently enrolling patients in a Phase 1b/2a clinical study in type 1 diabetes. Additionally, COUR has two partnered programs, one with Takeda Pharmaceuticals for celiac disease and with Genentech for an undisclosed program. Contacts For Investor Relations Brian Bock, Chief Financial Officer bbock@courpharma.com For Media Owen Blaschak oblaschak@lifescicomms.com References Corpechot, Christophe et al. “Liver stiffness measurement by vibration-controlled transient elastography improves outcome prediction in primary biliary cholangitis.” Journal of hepatology vol. 77,6 (2022): 1545-1553.doi:10.1016/j.jhep.2022.06.017 Study to Evaluate the Safety, Tolerability, PDs, and Efficacy of CNP-104 in Subjects with Primary Biliary Cholangitis.