Jascayd (nerandomilast) / Boehringer Ingelheim - LARVOL DELTA

Nerandomilast in Idiopathic Inflammatory Myopathy-Associated Interstitial Lung Disease: Subgroup Analysis of the Phase III FIBRONEER™-ILD Trial (ACR Convergence 2026) - "PPF was defined using INBUILD criteria.2 Concomitant nintedanib was permitted if the dose was stable. In this exploratory subgroup analysis of the FIBRONEER™-ILD trial, nerandomilast showed consistent trends toward reduced FVC decline and disease progression in patients with IIM-ILD. These findings, despite the small sample size, suggest that nerandomilast may have therapeutic potential in IIM-ILD."

P3 data • Idiopathic Pulmonary Fibrosis • Infectious Disease • Interstitial Lung Disease • Myositis • Pulmonary Disease • Respiratory Diseases

VERANDA™-SSc: Design of a Phase III, Double-blind, Randomized, Placebo-controlled Trial Evaluating the Safety and Efficacy of Oral Nerandomilast Treatment on Halting Disease Progression in Systemic Sclerosis (ACR Convergence 2026) - "The VERANDA™-SSc trial is a novel time-to-event-driven Phase III study evaluating the efficacy and safety of nerandomilast in patients with SSc, a disease for which there are no widely licensed pharmacological treatments targeting overall disease progression."

Clinical • P3 data • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • Scleroderma • Suicidal Ideation • Systemic Sclerosis • Vasculitis

Characterization of Weight Loss with Nerandomilast in Patients with Autoimmune Interstitial Lung Disease and Progressive Pulmonary Fibrosis in the FIBRONEER-ILD Trial (ACR Convergence 2026) - No abstract available

Clinical • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases

Characterization of Diarrhea Adverse Events with Nerandomilast in Patients with Autoimmune Interstitial Lung Disease and Progressive Pulmonary Fibrosis in the FIBRONEER-ILD Trial (ACR Convergence 2026) - No abstract available

Adverse events • Clinical • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases

Efficacy and Safety of Nerandomilast in Patients with Autoimmune-Interstitial Lung Disease (ILD) and Progressive Pulmonary Fibrosis in Subgroups by Time Since ILD Diagnosis (ACR Convergence 2026) - No abstract available

Clinical • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases

Nerandomilast, a Preferential Phosphodiesterase 4B Inhibitor, Dampens T-Cell Activation and Effector Function (ACR Convergence 2026) - No abstract available

Immunology • Inflammation

FIBRONEER-ACT: A Study to Test Whether Nerandomilast Helps People With Fibrosing Interstitial Lung Disease at Risk for Disease Progression (clinicaltrials.gov) - P3 | N=466 | Recruiting | Sponsor: Boehringer Ingelheim | Not yet recruiting ➔ Recruiting

Enrollment open • Fibrosis • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases

CON: not so fast – upfront combination therapy is not yet ready for routine practice (ERS 2026) - "While antifibrotic therapies such as nintedanib and pirfenidone have demonstrated efficacy in slowing disease progression, robust data supporting routine upfront combination therapy remain limited. Emerging therapies, including nerandomilast, have shown promising results in recent trials, but questions remain regarding optimal treatment sequencing, long-term safety, tolerability and cost-effectiveness when used in combination. This presentation will critically review the available evidence, highlight the gaps that still need to be addressed through dedicated clinical trials, and argue that a cautious, stepwise treatment approach remains the most appropriate strategy in current clinical practice for patients with fibrotic interstitial lung disease."

Combination therapy • Fibrosis • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases

Macrophage-fibroblast communication driven by biomechanical stress in the pulmonary profibrotic niche: From signalling transduction to clinical translation. (PubMed, Cells Dev) - "The three approved antifibrotic agents - pirfenidone, nintedanib, and nerandomilast - receive only moderate endorsements in current guidelines, as they decelerate rather than arrest or reverse fibrotic remodelling, and none directly engages the mechanical dysregulation of the extracellular matrix (ECM) that underlies fibrogenesis. Finally, we discuss the clinical translation of mechanosignalling-targeted antifibrotic therapies, from the limited mechanosensing engagement of approved drugs to current pipeline advances and the preclinical and clinical hurdles ahead. By framing fibrosis as a druggable biomechanical circuit, this review aims to inform strategies that halt - and potentially reverse - pulmonary fibrosis."

Journal • Review • Fibrosis • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases

iPSC organoid platform for fibrosis drug-discovery: Terminal/respiratory bronchiole secretory cell–aberrant-progeny crosstalk (ERS 2026) - "Responses to nintedanib, nerandomilast, and investigational new drug (IND) candidates were assessed. This iPSC-derived distal-lung organoid platform quantifies TRB-SC plasticity and epithelial–fibroblast communication relevant to pulmonary fibrosis and supports in vitro evaluation at scale of anti-fibrotic/regenerative candidates. HL001 showed anti-fibrotic activity consistent with alveolar regeneration that supports its FDA Orphan Drug Designation for IPF."

Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

PRO: upfront combination therapy in pulmonary fibrosis – start early, target more (ERS 2026) - "Building on current evidence with antifibrotic agents such as nintedanib, pirfenidone and nerandomilast, the presentation will discuss the limitations of monotherapy and the biological rationale for simultaneously targeting multiple profibrotic pathways. Drawing parallels with treatment strategies successfully implemented in other chronic conditions, such as pulmonary arterial hypertension, this presentation will argue that an upfront combination approach could be an effective next step in improving outcomes for patients with fibrotic interstitial lung diseases. Evidence, potential benefits and remaining challenges will be critically examined to support the case for a paradigm shift towards earlier, multitarget treatment strategies."

Combination therapy • Cardiovascular • Fibrosis • Immunology • Interstitial Lung Disease • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Mass spectrometry imaging of nintedanib and nerandomilast in normal and fibrotic mouse lungs and extrapulmonary organs (ERS 2026) - "[Methods] Pulmonary fibrosis was induced in mice by subcutaneous infusion of bleomycin. [Conclusions] MSI provides spatially resolved analysis of antifibrotic drug distribution and retention in normal and fibrotic lungs as well as other organs. This approach may support nonclinical evaluation of novel antifibrotic agents and help relate tissue exposure to efficacy and adverse events."

Preclinical • Fibrosis • Pulmonary Disease • Respiratory Diseases

The emerging role of PDE4 inhibitors for the treatment of pulmonary fibrosis. (PubMed, Expert Rev Clin Pharmacol) - "The pivotal FIBRONEER-IPF and FIBRONEER-ILD trials demonstrated significant reductions in the rate of FVC decline in patients with IPF and PPF, including those receiving background nintedanib therapy, establishing PDE4B inhibition as a new therapeutic strategy for pulmonary fibrosis. Beyond its demonstrated efficacy, nerandomilast represents a major therapeutic advance because of its favorable tolerability compared with earlier PDE4 inhibitors. As clinical experience with nerandomilast expands, real world data will be essential to better define its efficacy, tolerability, safety, and optimal clinical use."

Journal • Review • Idiopathic Pulmonary Fibrosis • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases • TGFB1

Anti-fibrotic effects of nerandomilast involving activated macrophages in a bleomycin-induced pulmonary fibrosis mouse model (ERS 2026) - "Consistently, in vitro experiments showed that activated macrophages under disease-mimicking conditions exhibited increased sensitivity to nerandomilast, leading to enhanced apoptotic responses. These findings indicate that nerandomilast exerts anti-fibrotic effects, by selectively inducing apoptosis in activated macrophages, thereby modulating macrophage dynamics during fibrosis progression."

Preclinical • Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

Clinical efficacy of pharmacological treatments for idiopathic pulmonary fibrosis: a systematic literature review (ERS 2026) - "Eighteen trials assessed pirfenidone (PIR) or nintedanib (NIN) as monotherapy...By treatment group, mCFB values were −30.9 to −95 mL with NIN 150 mg twice daily (NIN-150BID); −115 mL with nerandomilast 18 mg; −235 mL with PIR 2403 mg/day; and −183.5 to –428 mL with placebo (PBO)...Acute exacerbation rates over 52 weeks ranged 0%–33% across 7 trials, with NIN-150BID, 0%–6.1%; NIN-150BID + PIR 1200–1800 mg/day, 33%; PIR 2403 mg/day, 4%; PIR 2403 mg/day + sildenafil 60 mg/day, 11%; and PBO, 1.8%–15.7%... Variable efficacy of current therapies on lung function and acute exacerbations highlights the unmet need for better IPF therapies."

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

Reconfiguring the macrophage-centric intercellular network in pulmonary fibrosis: Emerging perspectives and therapeutic opportunities. (PubMed, Pharmacol Res) - "Currently, only nintedanib, pirfenidone, and the novel phosphodiesterase 4B (PDE4B) inhibitor nerandomilast have received regulatory approval for clinical use. Emphasis is placed on reviewing the pharmacological mechanisms and recent advances in natural active compounds targeting this core cellular network to intervene in PF. The objective is to offer a theoretical foundation for a more comprehensive understanding of PF pathogenesis and to facilitate the optimization and innovation of anti-fibrotic therapeutic strategies."

Journal • Review • Fibrosis • Immunology • Inflammation • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases

Nerandomilast (BI 1015550) attenuating pulmonary fibrosis in a mouse model of rheumatoid arthritis-associated interstitial lung disease by modulating the TGF-β1/PI3K/Akt signaling pathway. (PubMed, J Thorac Dis) - "A total of 20 male DBA/1 mice (a classic collagen-induced arthritis-susceptible strain) aged 8 weeks were randomly assigned to four groups: control (n=3), RA-ILD (n=5), nerandomilast (BI 1015550) (n=6), and nintedanib (n=6). Furthermore, the nerandomilast group showed significantly decreased p-PI3K/PI3K and p-Akt/Akt expression ratios compared with the RA-ILD group (P<0.05). Nerandomilast exerts significant protective effects against pulmonary inflammation and fibrosis in RA-ILD mice, potentially through the downregulation of TNF-α expression and modulation of the TGF-β1/PI3K/Akt signaling pathway."

Journal • Preclinical • Fibrosis • Immunology • Inflammatory Arthritis • Interstitial Lung Disease • Oncology • Pneumonia • Pulmonary Disease • Respiratory Diseases • Rheumatoid Arthritis • Rheumatology • MMP3 • TGFB1 • TNFA

Predicting long-term survival benefit of nerandomilast in patients with pulmonary fibrosis (ERS 2026) - " In patients not taking background antifibrotic therapy (nintedanib or pirfenidone), estimated median (Q1, Q3) survival was 3.8 (3.2, 4.7) years for placebo and 7.7 (5.5, 11.1) years for nerandomilast 18 mg bid. A model that extrapolated survival data from the FIBRONEER trials suggests a 3.9 year (2.0-fold) increase in median survival with nerandomilast 18 mg bid monotherapy versus no therapy, and a 1.2 year (1.3-fold) increase in median survival with nerandomilast 18 mg bid plus nintedanib versus nintedanib alone."

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

ASPIRE-IPF, a global, double-blind, randomized, placebo-controlled Phase 2b trial of buloxibutid, an angiotensin II type 2 receptor agonist, in idiopathic pulmonary fibrosis: trial design and patient characteristics (ERS 2026) - P2 | "Background therapy with nintedanib or nerandomilast is permitted... ASPIRE-IPF is one of the largest Phase 2b studies in IPF to date that aims to investigate the efficacy and safety of buloxibutid in IPF. Baseline data shows inclusion of a representative cohort of IPF participants."

Clinical • P2b data • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

Effect of nerandomilast in patients with progressive pulmonary fibrosis (PPF) according to guideline criteria: data from the FIBRONEER-ILD trial (ERS 2026) - " In the inclusion criteria for the FIBRONEER-ILD trial, PPF was defined using the same criteria as in the INBUILD trial of nintedanib. Most patients in the FIBRONEER-ILD trial met guideline criteria for PPF. The efficacy of nerandomilast was consistent between patients who met guideline criteria and the overall trial population."

Clinical • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases

Nerandomilast reduces AT2 senescence and maladaptive epithelial repair to attenuate fibrosis across acute and chronic bleomycin injury models (ERS 2026) - "Nerandomilast attenuates fibrotic progression across acute and chronic injury contexts by limiting AT2 senescence and maladaptive epithelial transitions, including PATS persistence and bronchiolisation-like distal remodeling."

Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • KRT5

Late Breaking Abstract - Safety and tolerability of nerandomilast in patients with idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF): data from FIBRONEER-ON (ERS 2026) - "At the start of FIBRONEER-ON, FVC was 74.7 and 71.4 % predicted in these groups, respectively; overall, 43.1% took nintedanib and 17.2% took pirfenidone. The favourable adverse event profile of nerandomilast supports sustained treatment in patients with IPF and PPF."

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

Identification of target of nerandomilast using alveolar type 2-specific gene knockout mice (ERS 2026) - "We further propose that this process of fibrotic microenvironment formation represents a potential target for nerandomilast. We report the targets of nerandomilast and nintedanib based on scRNA-seq of isolated mesenchymal cells derived from AT2-PtenKO mice and AT2-RhoAKO mice."

Preclinical • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Inflammation • Pneumonia • Pulmonary Disease • Respiratory Diseases • PTEN

Nerandomilast in patients with fibrosing ILDs at risk of developing progressive pulmonary fibrosis (PPF): design of the FIBRONEER-ACT trial (ERS 2026) - "Background: Patients with fibrosing ILDs other than idiopathic pulmonary fibrosis (IPF) are eligible for treatment with nintedanib or nerandomilast only once they have developed PPF. The FIBRONEER-ACT trial will assess the efficacy and safety of nerandomilast in patients with fibrosing ILDs at clinical risk of developing PPF, providing important information on the benefits of earlier treatment of fibrosing ILDs."

Clinical • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Inflammatory Arthritis • Pulmonary Disease • Respiratory Diseases • Rheumatoid Arthritis • Sarcoidosis

Effects of nerandomilast on plasma protein biomarkers in patients with idiopathic pulmonary fibrosis (IPF) (ERS 2026) - "These data suggest that nerandomilast has early antifibrotic, immunomodulatory and vascular effects in patients with IPF."

Biomarker • Clinical • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • CRP