CNP-104 / Cour Pharma, Ironwood Pharma - LARVOL DELTA

CNP-104 INDUCES ANTIGEN-SPECIFIC IMMUNE TOLERANCE IN PBC VIA PATHOGENIC CYTOKINE REDUCTION AND TOLEROGENIC T CELL EXPANSION (AASLD 2025) - "CNP-104 modulates PBC-relevant immune pathways by reducing pathogenic PDC-E2-specific Th17 cells and IL-17 while expanding tolerogenic TIGIT+ CD8+ T cells, demonstrating dual immune modulation toward tolerance. Furthermore, Th17 responders had a corresponding slowed progression of liver stiffness, suggesting a mechanism to explain CNP-104's anti-fibrotic effects. These findings support CNP-104 as a disease-modifying therapy that targets core immune dysfunction in PBC, with potential to improve outcomes beyond current standard of care."

IO biomarker • Fibrosis • Hepatology • Immune Modulation • Immunology • Inflammation • Primary Biliary Cholangitis • CD8 • IL17A • TIGIT

CNP-104 DEMONSTRATES CLINICAL BENEFITS IN PRIMARY BILIARY CHOLANGITIS (PBC) THROUGH IMPROVED COMPOSITE BIOCHEMICAL MARKERS AND PROGNOSTIC SCORES (AASLD 2025) - "CNP-104 improved UK-PBC and GLOBE scores, indicators of long-term risk reduction, in a treatment-refractory PBC population, highlighting its potential to modify disease course in those with limited therapeutic options. Notably, these benefits were observed after two loading doses, supporting further evaluation of a chronic dosing regimen in Phase 2b trials. CNP-104 represents a multidimensional therapeutic strategy for PBC patients, warranting advancement to confirmatory studies."

Clinical • IO biomarker • Hepatology • Immunology • Primary Biliary Cholangitis • CD99

Induction of Antigen-specific T Cell Tolerance by CNP-104 Positively Affects Clinical Response in Primary Biliary Cholangitis (PBC) (FOCIS 2025) - " We conducted a Phase 2a First-in-Human randomized controlled trial of CNP-104 in PBC patients unresponsive/intolerant to ursodeoxycholic acid. This trial is limited by small size and data variability. Induction of antigen-specific T cell tolerance, shown by reduced Th17 cells and increased TIGIT and GARP cells correlates with improved liver stiffness, albumin, and UK-PBC. These findings suggest the CNP-104 tolerogenic mechanism of action translates to clinical benefits."

Clinical • Immunology • Primary Biliary Cholangitis • CD8 • TIGIT

Induction of Antigen-Specific T Cell Tolerance by CNP-104 Positively Affects Clinical Response in Primary Biliary Cholangitis (PBC) (FOCIS 2025) - " We conducted a Phase 2a First-in-Human randomized controlled trial of CNP-104 in PBC patients unresponsive/intolerant to ursodeoxycholic acid. This trial is limited by small size and data variability. Induction of antigen-specific T cell tolerance, shown by reduced Th17 cells and increased TIGIT and GARP cells correlates with improved liver stiffness, albumin, and UK-PBC. These findings suggest the CNP-104 tolerogenic mechanism of action translates to clinical benefits."

Clinical • Immunology • Primary Biliary Cholangitis • CD8 • TIGIT

Induction of Antigen-Specific T Cell Tolerance by CNP-104 Positively Affects Clinical Response in Primary Biliary Cholangitis (PBC) (IMMUNOLOGY 2025) - "We conducted a Phase 2a First-in-Human randomized controlled trial of CNP-104 in PBC patients unresponsive/intolerant to ursodeoxycholic acid. These findings suggest the CNP-104 tolerogenic mechanism of action translates to clinical benefits. These data support future studies with this unique therapeutic platform to treat PBC.Keywords: Animals Human; Cells T Cells; Diseases Autoimmunity; Molecules Autoantibodies; Processes Tolerance/Suppression/Anergy"

Clinical • Late-breaking abstract • Hepatology • Immunology • Primary Biliary Cholangitis • CD8 • TIGIT

COUR Pharmaceuticals Secures FDA Orphan Drug Designation for CNP-104 in Primary Biliary Cholangitis (GlobeNewswire) - "COUR Pharmaceuticals...has secured Orphan Drug Designation (ODD) from the U.S. Food and Drug Administration (FDA) for CNP-104 for the treatment of primary biliary cholangitis (PBC)....This designation follows our presentation of positive topline data from the Phase 2a clinical trial of CNP-104 in PBC at The Liver Meeting 2024."

Orphan drug • Primary Biliary Cholangitis

Study to Evaluate the Safety, Tolerability, PDs, and Efficacy of CNP-104 in Subjects With Primary Biliary Cholangitis (clinicaltrials.gov) - P1/2 | N=42 | Active, not recruiting | Sponsor: COUR Pharmaceutical Development Company, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Hepatology • Immunology • Primary Biliary Cholangitis • IFNG • IL10 • IL1B • IL4 • IL6 • TNFA

Study to Evaluate the Safety, Tolerability, PDs, and Efficacy of CNP-104 in Subjects With Primary Biliary Cholangitis (clinicaltrials.gov) - P1/2 | N=40 | Recruiting | Sponsor: COUR Pharmaceutical Development Company, Inc. | Phase classification: P2a ➔ P1/2

Phase classification • Hepatology • Immunology • Primary Biliary Cholangitis • IFNG • IL10 • IL1B • IL4 • IL6 • TNFA

Study to Evaluate the Safety, Tolerability, PDs, and Efficacy of CNP-104 in Subjects With Primary Biliary Cholangitis (clinicaltrials.gov) - P2a | N=40 | Recruiting | Sponsor: COUR Pharmaceutical Development Company, Inc. | Trial completion date: Jun 2024 ➔ Dec 2025 | Trial primary completion date: Aug 2023 ➔ Dec 2025

Trial completion date • Trial primary completion date • Hepatology • Immunology • Primary Biliary Cholangitis • IL10 • IL4 • IL6

Study to Evaluate the Safety, Tolerability, PDs, and Efficacy of CNP-104 in Subjects With Primary Biliary Cholangitis (clinicaltrials.gov) - P2a | N=40 | Recruiting | Sponsor: COUR Pharmaceutical Development Company, Inc. | Trial completion date: Jun 2023 ➔ Jun 2024 | Trial primary completion date: Apr 2023 ➔ Aug 2023

Trial completion date • Trial primary completion date • Hepatology • Immunology • Primary Biliary Cholangitis • IL10 • IL4 • IL6

Study to Evaluate the Safety, Tolerability, PDs, and Efficacy of CNP-104 in Subjects With Primary Biliary Cholangitis (clinicaltrials.gov) - P2a | N=40 | Recruiting | Sponsor: COUR Pharmaceutical Development Company, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Hepatology • Immunology • Primary Biliary Cholangitis • IFNG • IL10 • IL1B • IL4 • IL6 • TNFA