nerandomilast (BI 1015550) / Boehringer Ingelheim - LARVOL DELTA

Insights Into the Cellular and Molecular Mechanisms Behind the Antifibrotic Effects of Nerandomilast. (PubMed, Am J Respir Cell Mol Biol) - "Treatment with nerandomilast significantly activated cAMP-associated pathways and G-protein-coupled receptor (GPCR) signaling events while inhibiting mitogen-activated protein kinase (MAPK) signaling pathways and transforming growth factor beta (TGFβ) signaling. These findings highlight nerandomilast's potential therapeutic use in IPF by providing insights into its cellular and molecular actions. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)."

Journal • Acute Lung Injury • Idiopathic Pulmonary Fibrosis • Immunology • Infectious Disease • Pulmonary Disease • Respiratory Diseases • VCAM1

FIBRONEER-ILD: A Study to Find Out Whether BI 1015550 Improves Lung Function in People With Progressive Fibrosing Interstitial Lung Diseases (PF-ILDs) (clinicaltrials.gov) - P3 | N=1178 | Completed | Sponsor: Boehringer Ingelheim | Active, not recruiting ➔ Completed

Trial completion • Fibrosis • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases

BI 1015550 Improves Silica-Induced Silicosis and LPS-Induced Acute Lung Injury in Mice. (PubMed, Molecules) - "Furthermore, we found that BI 1015550 could also alleviate lung inflammation in a Lipopolysaccharide (LPS)-induced acute lung injury mouse model. The mechanism of action may involve the regulation of cAMP-related signaling pathways."

Journal • Preclinical • Acute Lung Injury • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Inflammation • Interstitial Lung Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases • Scleroderma • Systemic Sclerosis

Initiation of Supplemental Oxygen in the FIBRONEER-IPF Trial of Nerandomilast in Patients With Idiopathic Pulmonary Fibrosis (ATS 2025) - No abstract available

Clinical • Late-breaking abstract • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

Nerandomilast Paves the Way for Novel Strategies in IPF Drug Discovery (ATS 2025) - No abstract available

Late-breaking abstract • Idiopathic Pulmonary Fibrosis

A Phosphodiesterase-4b Inhibitor, Nerandomilast Ameliorates Silica-induced Lung Inflammation and Fibrosis in Mice by Inhibiting NLRP3 Inflammasome Activation and the TGF-β/SMAD Pathway (ATS 2025) - No abstract available

Preclinical • Fibrosis • Immunology • Inflammation • Pneumonia • NLRP3 • TGFB1

ING-006, A Novel Oral GPR40/GPR84 Fatty Acid Receptor Modulator: A Comparative Study With Nintedanib and Nerandomilast (BI-1015550) in Bleomycin-induced Lung Fibrosis and CAM-IPF Xenograft Models (ATS 2025) - No abstract available

Preclinical • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Respiratory Diseases

A Comparative Study With ING-006, Nintedanib, Nerandomilast and Bexotegrast Using the In Vivo CAM-Patient-Derived IPF Model (ATS 2025) - No abstract available

Preclinical • Idiopathic Pulmonary Fibrosis

Exploration of Mechanism of Action of Nerandomilast in Pulmonary Fibrosis Through Single Cell Rna Sequence and Spatial Transcriptomic Analysis (ATS 2025) - No abstract available

Omic analysis • Immunology • Pulmonary Disease • Respiratory Diseases

Analysis of Local Distribution and Residence Time of Nerandomilast in Lung Tissue Using Mass Spectrometry Imaging (ATS 2025) - No abstract available

Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

Effects of Itraconazole, a Strong CYP3A Inhibitor, on Pharmacokinetics of Nerandomilast, a Preferential PDE4B Inhibitor (ATS 2025) - No abstract available

PK/PD data • Interstitial Lung Disease

Pharmacokinetics, Safety, and Tolerability of a Single Oral Dose of Nerandomilast (Bi 1015550) in Participants With and Without Renal Impairment (ATS 2025) - No abstract available

Clinical • PK/PD data • Renal Disease

Pharmacokinetics, Safety, And Tolerability Of A Single Oral Dose Of Nerandomilast (BI 1015550) In Participants With And Without Hepatic Impairment (ATS 2025) - No abstract available

Clinical • PK/PD data • Hepatology

A Study to Test Whether Nerandomilast Helps People With Lungfibrosis Related to Rheumatic Diseases (clinicaltrials.gov) - P3 | N=400 | Not yet recruiting | Sponsor: Boehringer Ingelheim | Initiation date: Mar 2025 ➔ Jul 2025

Trial initiation date • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases • Rheumatology

Boehringer’s nerandomilast meets primary endpoint in Phase III study FIBRONEER-ILD, in progressive pulmonary fibrosis (GlobeNewswire) - P3 | N=1178 | FIBRONEER-ILD (NCT05321082) | Sponsor: Boehringer Ingelheim | "Topline data from FIBRONEER-ILD show that the investigational compound nerandomilast met its primary endpoint, which was the absolute change from baseline in forced vital capacity [mL] at week 52 versus placebo; The FIBRONEER-ILD trial is the second Phase III trial in which the investigational compound nerandomilast has met its primary endpoint; Initial safety and tolerability results of the FIBRONEER-trials are generally consistent with the Phase II results in IPF; full efficacy and safety data from FIBRONEER-ILD will be shared in the second quarter of 2025; Boehringer Ingelheim will submit a new drug application for nerandomilast for the treatment of PPF to the US Food & Drug Administration (FDA) and other health authorities worldwide..."

P3 data: top line • Fibrosis • Pulmonary Disease

Synthesis of Carbon 14 and Deuterium-Labelled Nerandomilast (BI 1015550). (PubMed, J Labelled Comp Radiopharm) - "The carbon 14 synthesis was completed in three radioactive steps in 27% overall yield, with a specific activity of 52 mCi/mmol (1.92 GBq/mmol), radiochemical purity, and enantiomeric excess higher than 99%. The deuterium labelled compound was prepared in seven steps in 67% overall yield and with isotopic enrichment, chemical purity, and enantiomeric excess higher than 99%."

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

Boehringer Ingelheim Submits Marketing Application for Nerandomilast, an Innovative Pulmonary Fibrosis Therapy for Idiopathic Pulmonary Fibrosis [Google translation] (163.com) - "Boehringer Ingelheim announced today that its NMPA oral phosphodiesterase 4B (PDE4B) inhibitor nerandomilast has been accepted by the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) for the treatment of idiopathic pulmonary fibrosis (IPF) in adults. Previously, the therapy had been included in the CDE's priority review and approval process to accelerate its approval in China. The NMPA submission was based on the positive results of the pivotal Phase III clinical trial FIBRONEER-IPF of nerandomilast..."

China filing • Idiopathic Pulmonary Fibrosis

A Study to Test Whether Nerandomilast Helps People With Lungfibrosis Related to Rheumatic Diseases (clinicaltrials.gov) - P3 | N=400 | Not yet recruiting | Sponsor: Boehringer Ingelheim

New P3 trial • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases • Rheumatology

Boehringer Ingelheim’s first-in-class pulmonary fibrosis therapy granted priority review [Google translation] (Sohu.com) - "On January 24, the Center for Drug Evaluation (CDE) of the National Medical Products Administration officially granted priority review and approval to Boehringer Ingelheim's nerandomilast tablets, whose proposed indication is for the treatment of idiopathic pulmonary fibrosis (IPF) in adults....The pivotal Phase III clinical study FIBRONEER-IPF is the largest Phase III clinical study in the field of IPF treatment to date."

China approval • Priority review • Idiopathic Pulmonary Fibrosis

FIBRONEER-IPF: A Study to Find Out Whether BI 1015550 Improves Lung Function in People With Idiopathic Pulmonary Fibrosis (IPF) (clinicaltrials.gov) - P3 | N=1177 | Completed | Sponsor: Boehringer Ingelheim | Active, not recruiting ➔ Completed

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

Rationale for phosphodiesterase-4 inhibition as a treatment strategy for interstitial lung diseases associated with rheumatic diseases. (PubMed, RMD Open) - "The potential clinical benefit of PDE4B inhibition is now being investigated in the phase III setting, with two trials evaluating nerandomilast in patients with IPF (FIBRONEER-IPF) or with progressive pulmonary fibrosis other than IPF (FIBRONEER-ILD). Here, we review the preclinical and clinical data that provide rationale for PDE4B inhibition as a treatment strategy in patients with SARD-ILD."

Journal • Review • Fibrosis • Gastrointestinal Disorder • Idiopathic Pulmonary Fibrosis • Immunology • Inflammation • Inflammatory Arthritis • Interstitial Lung Disease • Musculoskeletal Diseases • Pulmonary Disease • Respiratory Diseases • Rheumatoid Arthritis • Rheumatology • Scleroderma • Systemic Sclerosis

A Study in Healthy People to Compare 2 Different Formulations of Nerandomilast Tablets When Taken With or Without Food (clinicaltrials.gov) - P1 | N=15 | Completed | Sponsor: Boehringer Ingelheim | Active, not recruiting ➔ Completed

Trial completion

A Study in Healthy People to Compare 2 Different Formulations of Nerandomilast Tablets When Taken With or Without Food (clinicaltrials.gov) - P1 | N=15 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Recruiting ➔ Active, not recruiting

Enrollment closed

Design of CONQUEST, a novel, randomized, placebo-controlled, Phase 2b platform clinical trial to investigate new treatments for patients with early active systemic sclerosis with interstitial lung disease. (PubMed, J Scleroderma Relat Disord) - P2 | "The first molecules to be studied, amlitelimab and nerandomilast, both have a strong scientific rationale to modify underlying disease processes in systemic sclerosis. Platform Clinical Study for Conquering Scleroderma (CONQUEST); NCT06195072; https://www.clinicaltrials.gov/study/NCT06195072."

Journal • P2b data • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases • Rheumatology • Scleroderma • Systemic Sclerosis

Nerandomilast Improves Bleomycin-Induced Systemic Sclerosis-Associated Interstitial Lung Disease in Mice by Regulating the TGF-β1 Pathway. (PubMed, Inflammation) - "Besides nintedanib and tocilizumab, there are currently no clinically approved drugs for SSc-ILD, highlighting the urgent need for new treatment strategies. Our research demonstrates that nerandomilast effectively inhibits skin and lung fibrosis in a bleomycin-induced mouse model of SSc-ILD. For lung fibrosis, we found that nerandomilast could improve bleomycin-induced SSc-ILD through inhibiting PDE4B and the TGF-β1-Smads/non-Smads signaling pathways, which provides a theoretical basis for potential therapeutic drug development for SSc-ILD."

Journal • Preclinical • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases • Rheumatology • Scleroderma • Systemic Sclerosis • TGFB1