nerandomilast (BI 1015550) / Boehringer Ingelheim - LARVOL DELTA

A Study in Healthy Men to Test How Bosentan Influences the Amount of Nerandomilast in the Blood (clinicaltrials.gov) - P1 | N=16 | Not yet recruiting | Sponsor: Boehringer Ingelheim

New P1 trial

First half of 2025: Solid growth, investments and pipeline progress pave the way for two key launches in H2 (GlobeNewswire) - "Boehringer Ingelheim...reported positive growth in the first half of 2025, with group net sales growing by 6.3% to EUR 14.0 billion. This performance was driven by strong demand for key products in Human Pharma, namely JARDIANCE with EUR 4.3 billion and OFEV with EUR 2.0 billion...Building on this momentum, the company is advancing its late-stage pipeline with several therapies nearing regulatory approval. Among these are zongertinib for HER2-mutant lung cancer and nerandomilast for pulmonary fibrosis, both of which recently delivered positive pivotal results...[Regulatory submissions underway for zongertinib and nerandomilast, with launches expected in H2 2025]"

Commercial • Filing • Launch • Heart Failure • Idiopathic Pulmonary Fibrosis • Interstitial Lung Disease • Non Small Cell Lung Cancer • Renal Disease • Type 2 Diabetes Mellitus

Late Breaking Abstract - Safety and tolerability of nerandomilast in patients with pulmonary fibrosis: pooled data from the FIBRONEER-IPF and FIBRONEER-ILD trials (ERS 2025) - No abstract available

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

Late Breaking Abstract - Effect of nerandomilast on clinical outcomes in patients with progressive pulmonary fibrosis (PPF): results from the final database lock of the FIBRONEER-ILD trial (ERS 2025) - No abstract available

Clinical • Clinical data • Late-breaking abstract • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases

Late Breaking Abstract - Effect of nerandomilast on clinical outcomes in patients with idiopathic pulmonary fibrosis (IPF): data from final database lock of the FIBRONEER-IPF trial (ERS 2025) - No abstract available

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

Late Breaking Abstract - Nerandomilast attenuates Pantoea agglomerans-induced hypersensitivity pneumonitis by regulating M1 macrophage and fibroblast (ERS 2025) - No abstract available

Late-breaking abstract • Immunology • Inflammation • Pneumonia • Pulmonary Disease

Effects of Nerandomilast on Alveolar Type 2 Cell Senescence and Fibrosis-Related PATS Accumulation in Pulmonary Fibrosis (ERS 2025) - No abstract available

Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

Effects of nerandomilast on pharmacokinetics of nintedanib and pirfenidone (ERS 2025) - No abstract available

PK/PD data • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases

Effect of nerandomilast in subgroups of patients with idiopathic pulmonary fibrosis (IPF) in the FIBRONEER-IPF trial (ERS 2025) - No abstract available

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

Initiation of supplemental oxygen in the FIBRONEER-IPF trial of nerandomilast in patients with idiopathic pulmonary fibrosis (ERS 2025) - No abstract available

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

Nerandomilast in progressive pulmonary fibrosis: results of the FIBRONEER-ILD trial (ERS 2025) - "Sponsored by Boehringer Ingelheim International GmbH"

Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases

Nerandomilast in idiopathic pulmonary fibrosis: results of the FIBRONEER-IPF trial (ERS 2025) - "Sponsored by Boehringer Ingelheim International GmbH"

Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

Nerandomilast slows progression of pulmonary fibrosis. (PubMed, Nat Rev Rheumatol) - No abstract available

Journal • Immunology • Pulmonary Disease • Respiratory Diseases

EFFECT OF NERANDOMILAST IN US PATIENTS WITH IDIOPATHIC PULMONARY FIBROSIS: SUBGROUP ANALYSIS OF THE FIBRONEER-IPF TRIAL (CHEST 2025) - No abstract available

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

A Study in People With Idiopathic Pulmonary Fibrosis to Test Whether Pirfenidone Influences the Amount of BI 1015550 in the Blood (clinicaltrials.gov) - P2 | N=20 | Not yet recruiting | Sponsor: Boehringer Ingelheim | Trial completion date: Oct 2025 ➔ Jan 2026 | Trial primary completion date: Oct 2025 ➔ Jan 2026

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

Efficacy and safety of nerandomilast in patients with autoimmune disease–related progressive pulmonary fibrosis: subgroup analysis of the FIBRONEER-ILD trial (EULAR 2025) - "Use of cyclophosphamide, tocilizumab, mycophenolate, or rituximab was not permitted at enrolment but could be initiated after 6 months to manageworsening systemic disease. Prednisone >15 mg/day (or equivalent) was not permitted at enrolment but could be prescribed during the trial for acute exacerbation of ILD...At baseline, among patients with autoimmune ILDs, 212 (65.2%) were female, mean (SD) age was 63.4 (11.2) years, FVC was 71.5 (15.0) % predicted, diffusing capacity for carbon monoxide (DLco) was 51.5 (16.8) % predicted; 111 (34.2%) patients were taking nintedanib... In the FIBRONEER-ILD trial, the efficacy of nerandomilast on slowing decline in FVC in patients with autoimmune ILDs was consistent with that observed in the overall trial population. Nerandomilast had an acceptable safety and tolerability profile, with serious adverse events and treatment discontinuations being no more common in patients who received nerandomilast than placebo."

Clinical • Late-breaking abstract • Idiopathic Pulmonary Fibrosis • Immunology • Inflammatory Arthritis • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases • Rheumatoid Arthritis • Rheumatology • Scleroderma • Systemic Sclerosis

Initiation of Supplemental Oxygen in the FIBRONEER-IPF Trial of Nerandomilast in Patients With Idiopathic Pulmonary Fibrosis (ATS 2025) - " Patients with IPF were randomized 1:1:1 to receive nerandomilast 9 mg bid, nerandomilast 18 mg bid, or placebo, stratified by background antifibrotic therapy (nintedanib/pirfenidone vs none). In the FIBRONEER-IPF trial in patients with IPF, a reduced risk of initiation of supplemental oxygen during follow-up was observed in patients receiving nerandomilast 9mg bid versus placebo."

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

Inhaled PDE4 Inhibitor F2008 Alleviates Bleomycin-Induced Pulmonary Fibrosis (ATS 2025) - "A bleomycin-induced PF mouse model was established, and inhalation with 2mg/kg F2008 was administered from Day 2 to Day 21 (oral administration of nintedanib or BI-1015550 was used as a positive control). F2008 inhalation achieves high pulmonary retention, and exhibiting robust anti-inflammatory and antifibrotic effects in a bleomycin-induced PF mouse model. Collectively, F2008 represents a promising inhaled PDE4i for the treatment of IPF."

Late-breaking abstract • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • IL6 • TGFB1

Cyclic AMP Signaling Within Lung Fibroblasts Promotes the Clearance of Pathologic Epithelial and Macrophage Subtypes During Spontaneous Fibrosis Resolution (ATS 2025) - "Although the molecular mechanisms and cellular crosstalk that promote clearance of these cells remains a critical gap in knowledge, spontaneously resolving models of pulmonary fibrosis - such as single-dose bleomycin in young mice - provide a unique opportunity to identify endogenous molecular brakes responsible for orchestrating these crucial events. The second messenger cyclic AMP (cAMP) has garnered renewed attention with nerandomilast (a PDE4B inhibitor that increases intracellular cAMP) recently achieving its primary endpoint in a phase 3 trial...Tamoxifen chow was introduced to abolish Gαs expression in fibroblasts at day 21 (peak fibrosis)... Lung fibroblast-specific cAMP generation is a crucial endogenous brake that promotes fibrosis resolution through fibroblast deactivation/apoptosis and timely clearance of aberrant macrophages and epithelial cells. These findings highlight the importance of fibroblast-mediated cellular crosstalk in fibrosis resolution and..."

Late-breaking abstract • Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • C1QB • CLDN4 • COL1A2 • GNAS • ITGAX

Nerandomilast Paves the Way for Novel Strategies in IPF Drug Discovery (ATS 2025) - "These effects were linked to activated cAMP-associated pathways, G-protein-coupled receptor (GPCR) signaling events, mitogen-activated protein kinase (MAPK) signaling pathways and transforming growth factor beta 1(TGFβ1) signaling. Nerandomilast's efficacy in IPF may be attributable to effects on an array of patho-mechanisms in epithelial, endothelial, and immune cells, in addition to fibroblasts. Cutting edge technologies can build on such principles to transform drug discovery strategies. Next generation targets will influence our newly characterized pathologic niches, with the bold aim to not only limit disease but return functionality to the lung."

Late-breaking abstract • Acute Lung Injury • Idiopathic Pulmonary Fibrosis • Immunology • Infectious Disease

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) - "Fibronectin and collagen I expression in MRC-5 fibroblasts, cultured with silica-treated macrophage supernatants, were elevated but decreased following Nerandomilast treatment. CONCLUSIONS The PDE4B inhibitor, Nerandomilast effectively suppressed silica-induced inflammation via the NLRP3 Inflammasome pathway and lung fibrosis through the TGF-β/Smad pathway, highlighting its potential as a therapeutic option for the currently untreatable silicosis."

Late-breaking abstract • Preclinical • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Inflammation • Pneumonia • FN1 • NLRP3 • TGFB1

Exploration of Mechanism of Action of Nerandomilast in Pulmonary Fibrosis Through Single Cell Rna Sequence and Spatial Transcriptomic Analysis (ATS 2025) - "Bleomycin (BLM)-challenged mice were treated with Nerandomilastor placebo twice daily, starting 8 days after BLM administration. CONCLUSIONS Nerandomilast reducedlung fibrosis and inflammatory response. The abundance of fibrosis specimensand detailed analysis of mouse models, coupled with scRNA-seq and spatialtranscriptomic analysis, revealed the details of Nerandomilast's mechanism ofaction on fibrosis and inflammation."

Omic analysis • Fibrosis • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases

Buloxibutid Potently Inhibits Fibrosis Biomarkers in the Scar-in-a-Jar Primary Human Lung Fibroblast Assay (ATS 2025) - "This abstract is funded by: Vicore Pharma RATIONALE In a recent open-label Phase 2a clinical trial, the selective, orally available angiotensin II type 2 receptor (AT2R) agonist buloxibutid (also known as C21) improved lung function in patients with idiopathic pulmonary fibrosis (IPF) over a 36-week period. CONCLUSION The findings demonstrate that buloxibutid potently inhibits collagen synthesis in activated human lung fibroblasts, demonstrating its potential as an effective antifibrotic IPF therapy. Buloxibutid was more potent than nintedanib and nerandomilast."

Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • TGFB1

Analysis of Local Distribution and Residence Time of Nerandomilast in Lung Tissue Using Mass Spectrometry Imaging (ATS 2025) - "In this study, we investigated the local distribution and residence time of nerandomilast in lung tissue using MSI, and compared them with nintedanib. Boehringer Ingelheim had no role in the design, analysis or interpretation of the results in this study . Boehringer Ingelheim was given the opportunity to review the manuscript for medical and scientific accuracy as it relates to Boehringer Ingelheim substances, as well as intellectual property considerations.]"

Immunology • Pulmonary Disease • Respiratory Diseases

Effects of Itraconazole, a Strong CYP3A Inhibitor, on Pharmacokinetics of Nerandomilast, a Preferential PDE4B Inhibitor (ATS 2025) - "Drugs that are strong CYP3A inhibitors may increase the exposure of nerandomilast up to 2-fold. A less prominent exposure increase is expected when nerandomilast is co-administered with moderate or mild CYP3A4 inhibitors."

PK/PD data • Idiopathic Pulmonary Fibrosis • Immunology • Interstitial Lung Disease