ND-L02-s0201 / Nitto Denko, BMS - LARVOL DELTA

Safety and Effectiveness of BMS-986263 in Adults With Compensated Cirrhosis (Liver Disease) From Nonalcoholic Steatohepatitis (NASH) (clinicaltrials.gov) - P2 | N=124 | Terminated | Sponsor: Bristol-Myers Squibb | Trial completion date: Dec 2026 ➔ Feb 2024 | Active, not recruiting ➔ Terminated; Trial terminated because of lack of efficacy in the short term acute phase.

Trial completion date • Trial termination • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Metabolic Dysfunction-Associated Steatohepatitis

Safety and Effectiveness of BMS-986263 in Adults With Compensated Cirrhosis (Liver Disease) From Nonalcoholic Steatohepatitis (NASH) (clinicaltrials.gov) - P2 | N=124 | Active, not recruiting | Sponsor: Bristol-Myers Squibb | N=270 ➔ 124 | Trial primary completion date: Aug 2026 ➔ Aug 2023

Enrollment change • Trial primary completion date • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Non-alcoholic Steatohepatitis

Pharmacokinetics, safety, and tolerability of BMS-986263, a lipid nanoparticle containing HSP47 siRNA, in participants with hepatic impairment. (PubMed, Clin Transl Sci) - "Overall, single-dose BMS-986263 was generally safe and well-tolerated and dose adjustment is not considered necessary for participants with mild or moderate HI. Although available data do not indicate that dose adjustment should be performed in patients with severe HI; the optimal posology of BMS-986263 in patients with severe HI may be determined later in its clinical development when additional data to establish exposure-safety/efficacy relationship becomes available."

Journal • PK/PD data • Fibrosis • Hepatology • Immunology • SERPINH1

Safety and Effectiveness of BMS-986263 in Adults With Compensated Cirrhosis (Liver Disease) From Nonalcoholic Steatohepatitis (NASH) (clinicaltrials.gov) - P2 | N=270 | Active, not recruiting | Sponsor: Bristol-Myers Squibb | Recruiting ➔ Active, not recruiting

Enrollment closed • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Non-alcoholic Steatohepatitis

Safety and Effectiveness of BMS-986263 in Adults With Compensated Cirrhosis (Liver Disease) From Nonalcoholic Steatohepatitis (NASH) (clinicaltrials.gov) - P2 | N=270 | Recruiting | Sponsor: Bristol-Myers Squibb | Trial completion date: Jul 2024 ➔ Dec 2026 | Trial primary completion date: Mar 2024 ➔ Aug 2026

Trial completion date • Trial primary completion date • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Non-alcoholic Steatohepatitis

JUNIPER: A Phase 2 Study to Evaluate the Safety, Biological Activity, and PK of ND-L02-s0201 in Subjects With IPF (clinicaltrials.gov) - P2 | N=123 | Completed | Sponsor: Nitto Denko Corporation | Active, not recruiting ➔ Completed

Trial completion • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

Safety and Effectiveness of BMS-986263 in Adults With Compensated Cirrhosis (Liver Disease) From Nonalcoholic Steatohepatitis (NASH) (clinicaltrials.gov) - P2; N=270; Recruiting; Sponsor: Bristol-Myers Squibb; Not yet recruiting ➔ Recruiting; Trial completion date: May 2023 ➔ Jan 2024; Trial primary completion date: Apr 2023 ➔ Jul 2023

Clinical • Enrollment open • Trial completion date • Trial primary completion date • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Non-alcoholic Steatohepatitis

Safety and Effectiveness of BMS-986263 in Adults With Compensated Cirrhosis (Liver Disease) From Nonalcoholic Steatohepatitis (NASH) (clinicaltrials.gov) - P2; N=270; Recruiting; Sponsor: Bristol-Myers Squibb; Trial completion date: Jan 2024 ➔ Jul 2024; Trial primary completion date: Jul 2023 ➔ Mar 2024

Clinical • Trial completion date • Trial primary completion date • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Non-alcoholic Steatohepatitis

Pharmacokinetics, safety, and tolerability of BMS-986263, a lipid nanoparticle containing HSP47 siRNA, in participants with severe hepatic impairment (EASL-ILC 2022) - P1, P2 | "Single-dose BMS-986263 was generally safe and welltolerated in ppts with severe HI. The PK of some BMS-986263 components were affected by severe HI; increased exposure of siRNA and S104 (163% and 452%, respectively) was observed in ppts with severe HI compared with normal-matched ppts."

Clinical • PK/PD data • Back Pain • Fibrosis • Hepatology • Immunology • Musculoskeletal Pain • Non-alcoholic Steatohepatitis • Pain • SERPINH1

JUNIPER: A Phase 2 Study to Evaluate the Safety, Biological Activity, and PK of ND-L02-s0201 in Subjects With IPF (clinicaltrials.gov) - P2; N=120; Active, not recruiting; Sponsor: Nitto Denko Corporation; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

A Single-dose Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of BMS-986263 in Participants With Varying Degrees of Liver Impairment (clinicaltrials.gov) - P1; N=40; Completed; Sponsor: Bristol-Myers Squibb; Recruiting ➔ Completed

Clinical • Trial completion • Hepatology

[VIRTUAL] PHARMACOKINETICS, SAFETY, AND TOLERABILITY OF BMS- 986263, A LIPID NANOPARTICLE CONTAINING HSP47 siRNA, IN PARTICIPANTS WITH HEPATIC IMPAIRMENT (AASLD 2021) - P1 | "Single-dose BMS-986263 PK was modestly affected by mild to moderate HI and was generally safe and well tolerated . Results from Part 1 of this study support enrollment of ppts with mild HI in future BMS-986263 clinical trials."

Clinical • PK/PD data • Fibrosis • Hepatology • Immunology • Non-alcoholic Steatohepatitis • SERPINH1

BMS-986263 in Patients with Advanced Hepatic Fibrosis: 36-Week Results from a Randomized, Placebo-Controlled Phase 2 Trial. (PubMed, Hepatology) - P2 | "In patients with HCV-SVR, BMS-986263 administration was generally well tolerated through Week 36 and resulted in METAVIR and Ishak score improvements. Further evaluation of BMS-986263 in patients with active fibrogenesis is warranted."

Clinical • Journal • P2 data • Fibrosis • Hepatitis C • Hepatology • Immunology • Infectious Disease • Inflammation • Liver Failure • SERPINH1

JUNIPER: A Phase 2 Study to Evaluate the Safety, Biological Activity, and PK of ND-L02-s0201 in Subjects With IPF (clinicaltrials.gov) - P2; N=120; Recruiting; Sponsor: Nitto Denko Corporation; Trial completion date: Sep 2021 ➔ Sep 2022; Trial primary completion date: Jul 2021 ➔ Aug 2022

Clinical • Trial completion date • Trial primary completion date • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

Anti-HSP47 siRNA lipid nanoparticle ND-L02-s0201 reverses interstitial pulmonary fibrosis in preclinical rat models. (PubMed, ERJ Open Res) - "Comprehensive optimisation and characterisation of bleomycin (BLM) and silica-induced rat lung fibrosis models were conducted, which ensured progressive pathological changes were sustained throughout the study during evaluation of the anti-fibrotic potential of ND-L02-s0201. Comparable anti-fibrotic efficacy was also observed in the silica model. Results from two robust chronic rodent models of pulmonary fibrosis demonstrated significant anti-fibrotic effects and improved lung function which support the evaluation of ND-L02-s0201 in subjects with idiopathic pulmonary fibrosis."

Journal • Preclinical • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • SERPINH1

A Single-dose Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of BMS-986263 in Participants With Varying Degrees of Liver Impairment (clinicaltrials.gov) - P1; N=32; Recruiting; Sponsor: Bristol-Myers Squibb; Trial completion date: Dec 2020 ➔ Jun 2021; Trial primary completion date: Dec 2020 ➔ Jun 2021

Clinical • Trial completion date • Trial primary completion date • Hepatology

[VIRTUAL] BMS-986263 (NOVEL TARGETED LIPID NANOPARTICLE DELIVERING HSP47 siRNA) SAFETY AND TARGET ENGAGEMENT IN PATIENTS WITH ADVANCED HEPATIC FIBROSIS: WEEK 36 RESULTS FROM A PHASE 2 RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL (AASLD 2020) - P2 | "In this study of a limited number of pts with HCV-SVR and fibrosis, BMS-986263 IV QW x12 wks demonstrated TE by reducing liver HSP47 mRNA. The majority of METAVIR and Ishak responders had improved qFIB. BMS-986263 was generally well tolerated through wk 36."

Clinical • P2 data • Fibrosis • Hepatitis C • Hepatology • Immunology • Infectious Disease • Liver Cirrhosis • SERPINH1

Safety and effectiveness of BMS-986263 in adults with compensated cirrhosis (liver disease) from nonalcoholic steatohepatitis (NASH). (clinicaltrialsregister.eu) - P2; N=270; Ongoing; Sponsor: Bristol-Myers Squibb International Corporation

Clinical • New P2 trial • Fibrosis • Gastroenterology • Hepatology • Immunology • Liver Cirrhosis • Non-alcoholic Steatohepatitis

A Single-dose Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of BMS-986263 in Participants With Varying Degrees of Liver Impairment (clinicaltrials.gov) - P1; N=40; Recruiting; Sponsor: Bristol-Myers Squibb; Active, not recruiting ➔ Recruiting

Clinical • Enrollment open

A Fit-for-Purpose Method for the Detection of Human Antibodies to Surface-Exposed Components of BMS-986263, a Lipid Nanoparticle-Based Drug Product Containing a siRNA Drug Substance. (PubMed, AAPS J) - "Based on these results, we concluded that BMS-986263 is not immunogenic. To the best of our knowledge, this work represents the first ADA method developed and reported for an LNP-based drug product."

Journal • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Respiratory Diseases

Phase 1b/2, Open Label, Repeat Dose, Dose Escalation Study of ND-L02-s0201 Injection in Subjects With Moderate to Extensive Fibrosis (METAVIR F3-4) (clinicaltrials.gov) - P1; N=24; Not yet recruiting; Sponsor: Nitto Denko Corporation

New P1 trial • Biosimilar • Chronic Kidney Disease • Fibrosis

JUNIPER: A Phase 2 Study to Evaluate the Safety, Biological Activity, and PK of ND-L02-s0201 in Subjects With IPF (clinicaltrials.gov) - P2; N=120; Recruiting; Sponsor: Nitto Denko Corporation; Trial completion date: Jan 2021 ➔ Sep 2021; Trial primary completion date: Mar 2020 ➔ Jul 2021

Clinical • Trial completion date • Trial primary completion date