brensocatib (INS1007) / Insmed, AstraZeneca - LARVOL DELTA

Insmed to Present 11 Abstracts from Across Its Respiratory Portfolio at the American Thoracic Society 2025 International Conference (PRNewswire) - "Presentations include several prespecified subgroup analyses from the Phase 3 ASPEN study evaluating the efficacy and safety of brensocatib, new health economics and outcomes research in MAC lung disease, and clinical data from the Phase 2a study of treprostinil palmitil inhalation powder (TPIP) in pulmonary hypertension associated with interstitial lung disease (PH-ILD).1"

Clinical data • Bronchiectasis • Interstitial Lung Disease • Non‐Cystic Fibrosis Bronchiectasis

Efficacy of Brensocatib in Patients With Eosinophilic Bronchiectasis: An Analysis of the ASPEN Trial (ATS 2025) - No abstract available

Clinical • Bronchiectasis • Pulmonary Disease • Respiratory Diseases

Insmed Reports Fourth-Quarter and Full-Year 2024 Financial Results and Provides Business Update (PRNewswire) - "ARIKAYCE global revenue grew 19% in 2024 compared to 2023...The Company continues to anticipate a topline readout for ENCORE in the first quarter of 2026, with the submission of a supplementary new drug application (sNDA) to the FDA for ARIKAYCE in all patients with MAC lung disease in the U.S. expected later in 2026...Regulatory submissions for brensocatib in the EU, UK, and Japan are planned for 2025, with commercial launches anticipated in 2026...The Phase 2b BiRCh study of brensocatib in patients with chronic rhinosinusitis without nasal polyps (CRSsNP) remains on track to report topline results by the end of 2025...The Company plans to initiate a Phase 3 study of TPIP in patients with PH-ILD in the second half of 2025. Enrollment in the Phase 2b study of TPIP in pulmonary arterial hypertension (PAH) completed in December 2024...Insmed continues to anticipate topline data from the study in the middle of 2025."

Commercial • Filing • New P3 trial • P2b data • P3 data: top line • Infectious Disease • Nasal Polyps • Pulmonary Arterial Hypertension • Pulmonary Disease

Efficacy of Brensocatib in Patients With Non-Cystic Fibrosis Bronchiectasis With vs Without Maintenance Use of Macrolides: An Analysis of the ASPEN Trial (ATS 2025) - No abstract available

Clinical • Bronchiectasis • Genetic Disorders • Immunology • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases

Salivary Dipeptidyl Peptidase-1 and Derived Proinflammatory Markers in Primary Ciliary Dyskinesia Patients: Implications for Brensocatib Therapy (ATS 2025) - No abstract available

Clinical • Otorhinolaryngology • Respiratory Diseases

Insmed Announces that FDA Does Not Currently Plan to Hold Advisory Committee Meeting to Discuss New Drug Application for Brensocatib in Patients with Bronchiectasis (PRNewswire) - "Insmed Incorporated...today announced that the U.S. Food and Drug Administration (FDA) has informed the Company that it does not currently plan to hold an advisory committee meeting to discuss the New Drug Application (NDA) for brensocatib for patients with non-cystic fibrosis bronchiectasis. The FDA provided this update in its Day 74 communication to Insmed."

FDA event • Bronchiectasis

FDA Grants Priority Review to Insmed’s Brensocatib for Treatment of Bronchiectasis with PDUFA Target Action Date Set for August 12, 2025 (PRNewswire) - "Insmed Incorporated...announced that the U.S. Food and Drug Administration (FDA) has accepted the Company's New Drug Application (NDA) for brensocatib for patients with non-cystic fibrosis bronchiectasis. In its Day 60 communication to Insmed, the FDA granted Priority Review to the NDA and set a target action date of August 12, 2025, under the Prescription Drug User Fee Act (PDUFA). At present, the FDA has not indicated whether an advisory committee will be convened to discuss the application....This NDA is based on data from the landmark Phase 3 ASPEN study, which met its primary endpoint with both dosage strengths of brensocatib achieving statistical and clinical significance for the reduction in the annualized rate of pulmonary exacerbations versus placebo over the 52-week treatment period....Insmed plans to file regulatory submissions for brensocatib in the EU, UK, and Japan in 2025, with commercial launches anticipated in 2026, pending approval in each territory."

Filing • Launch • PDUFA • Priority review • Non‐Cystic Fibrosis Bronchiectasis

Broad Immunomodulatory Effects of the Dipeptidyl-peptidase-1 Inhibitor Brensocatib in Bronchiectasis: Data from the Phase 2, Double-Blind, Place-controlled WILLOW Trial. (PubMed, Am J Respir Crit Care Med) - P2 | "Brensocatib exerts broad anti-inflammatory effects beyond its known effects on serine proteases. Clinical trial registration available at www."

Journal • P2 data • Bronchiectasis • Inflammation • Pulmonary Disease • Respiratory Diseases • CCL11 • CCL3 • CCL8 • CXCL10 • ELANE • IL6 • IL7 • MPO • MUC5AC

Brensocatib in patients with bronchiectasis: subgroup analyses from the WILLOW trial. (PubMed, ERJ Open Res) - "Safety results were similar across subgroups. Patients treated with brensocatib had a numerically longer time to first exacerbation and reduced annualised rate of exacerbation versus placebo across all key baseline disease characteristics."

Journal • Bronchiectasis • Inflammation • Pneumonia • Pulmonary Disease • Respiratory Diseases

Evaluation of Neutrophil Elastase Inhibitors as Potential Therapies for ELANE Associated Neutropenia. (PubMed, J Cell Immunol) - "In contrast, other NE inhibitors, i.e., sivelestat, BAY-678, and GW311616 and the DPP1 inhibitor, brensocatib, showed no effect on neutrophil differentiation. Molecular docking studies showed that MK0339 binds to an alternative site on the NE protein compared to other inhibitors with greater inhibitor-NE protein stability, suggesting a unique mechanism of action and supporting further investigation of MK0339 as a therapy for ELANE associated neutropenia."

Journal • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Musculoskeletal Pain • Myelodysplastic Syndrome • Neutropenia • Oncology • Pain • Transplantation • CD14 • CD34 • CEACAM8 • ELANE • ITGAM

CEDAR: A Study of the Efficacy and Safety of Brensocatib in Adults With Moderate to Severe Hidradenitis Suppurativa (HS) (clinicaltrials.gov) - P2 | N=204 | Recruiting | Sponsor: Insmed Incorporated | Not yet recruiting ➔ Recruiting

Enrollment open • Dermatology • Hidradenitis Suppurativa • Immunology

Brensocatib: “The primary endpoint was met, with both brensocatib 10 mg and 25 mg significantly reducing the annualized rate of adjudicated pulmonary exacerbations over 52 weeks vs placebo by 21% (rate ratio, 0.79; 95% CI; 0.68-0.92; P=0.0019) and 19% (rate ratio, 0.81; 95% CI, 0.69-0.94; P=0.0046), respectively”; Bronchiectasis (Insmed, Inc) - Phase 3 ASPEN Subpopulation Data Presentation at the 2024 CHEST Annual Meeting

P3 data • Bronchiectasis

Insmed Reports Third-Quarter 2024 Financial Results and Provides Business Update (PRNewswire) - "Selling, general and administrative (SG&A) expenses for the third quarter of 2024 were $118.9 million, compared to $90.6 million for the third quarter of 2023. The year-over-year increase in SG&A expenses resulted primarily from increases in compensation and benefit-related expenses and stock-based compensation costs due to an increase in headcount associated with launch readiness activities for brensocatib."

Commercial • Non‐Cystic Fibrosis Bronchiectasis

Brensocatib: “Overall, lung function in the placebo group declined at week 52 from baseline by 62 mL”; Bronchiectasis (Insmed, Inc) - Phase 3 ASPEN Subpopulation Data Presentation at the 2024 CHEST Annual Meeting

P3 data • Bronchiectasis

ASPEN: A Study to Assess the Efficacy, Safety, and Tolerability of Brensocatib in Participants With Non-Cystic Fibrosis Bronchiectasis (clinicaltrials.gov) - P3 | N=1767 | Completed | Sponsor: Insmed Incorporated | Active, not recruiting ➔ Completed | Trial completion date: Mar 2024 ➔ Oct 2024 | Trial primary completion date: Mar 2024 ➔ Oct 2024

Trial completion • Trial completion date • Trial primary completion date • Bronchiectasis • Genetic Disorders • Immunology • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases

CEDAR: A Study of the Efficacy and Safety of Brensocatib in Adults With Moderate to Severe Hidradenitis Suppurativa (HS) (clinicaltrials.gov) - P2 | N=204 | Not yet recruiting | Sponsor: Insmed Incorporated

New P2 trial • Dermatology • Hidradenitis Suppurativa • Immunology

Immunomodulatory effects of the Dipeptidyl peptidase-1 inhibitor brensocatib in patients with bronchiectasis: data from the phase 2 WILLOW trial (BTS WM 2024) - P2, P3 | "Interpretation Brensocatib exerts broad anti-inflammatory effects. Its efficacy may relate to downstream improvements in host defence in addition to recognized effects on NSPs."

Clinical • Immunomodulating • P2 data • Bronchiectasis • Infectious Disease • Inflammation • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases • CCL11 • CCL3 • CCL8 • CXCL10 • ELANE • IL6 • IL7 • MPO • MUC5AC

The pharmacokinetics of brensocatib in participants with renal impairment following a single oral administration. (PubMed, Br J Clin Pharmacol) - P1 | "Single-dose brensocatib was well tolerated. The study data do not indicate a significant effect of renal impairment on brensocatib elimination and systemic exposure, suggesting that dose adjustment of brensocatib is not necessary in participants with renal impairment."

Journal • PK/PD data • Bronchiectasis • Pulmonary Disease • Renal Disease • Respiratory Diseases

Increased expression of Cathepsin C in airway epithelia exacerbates airway remodeling in asthma. (PubMed, JCI Insight) - "Consequently, targeting CTSC with compound AZD7986 protected against airway inflammation, EMTU activation and remodeling in asthma model. Based on the dual effects of CTSC on airway inflammation and remodeling, CTSC is a potential biomarker and therapeutic target for SA or UA."

Journal • Asthma • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • CTSC

Safety profile of drugs used in non-cystic fibrosis bronchiectasis: a narrative review. (PubMed, Ther Adv Drug Saf) - "Most of the drugs used in daily clinical practice for bronchiectasis are off-label with no randomised trials exploring their safety. This review aims at exploring the safety profile of drugs frequently used in clinical practice to manage bronchiectasis, including antibiotics (e.g. macrolides, aminoglycosides, polymyxins, fluoroquinolones, aztreonam), mucoactive therapy (e.g. hypertonic saline, mannitol, DNase and carbocisteine), anti-inflammatory therapy (inhaled corticosteroids) and drugs currently in development for use in bronchiectasis (e.g. brensocatib, benralizumab and itepekimab)."

Journal • Review • Bronchiectasis • Cough • Genetic Disorders • Immunology • Infectious Disease • Inflammation • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases

LUNG FUNCTION IN PATIENTS WITH NON-CYSTIC FIBROSIS BRONCHIECTASIS BY PRESPECIFIED SUBGROUPS IN THE PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED ASPEN TRIAL (CHEST 2024) - P3 | "The pivotal phase 3 ASPEN trial evaluating the efficacy and safety of brensocatib is the largest bronchiectasis global clinical trial program to date, enrolling over 1700 patients spanning 35 countries and 5 continents. The analyses presented will establish if the efficacy of brensocatib is consistent across disease subgroups, an important endeavor in a disease as heterogeneous as bronchiectasis. CLINICAL IMPLICATIONS: There are currently no indicated treatments for bronchiectasis approved by the FDA or EMA."

Clinical • P3 data • Bronchiectasis • Genetic Disorders • Immunology • Inflammation • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases • ELANE

New Subgroup Analyses from Landmark Phase 3 ASPEN Study of Brensocatib in Patients with Bronchiectasis Demonstrate Consistency with Positive Overall Trial Population Results (PRNewswire) - P3 | N=1,767 | ASPEN (NCT04594369) | Sponsor: Insmed Incorporated | "Insmed Incorporated...presented positive late-breaking subgroup data from the Phase 3 ASPEN study, a global, randomized, double-blind, placebo-controlled Phase 3 study to assess the efficacy, safety, and tolerability of brensocatib in patients with non-cystic fibrosis bronchiectasis...at the CHEST 2024 Annual Meeting....Consistent with positive results for the overall ASPEN population, the annualized rate of pulmonary exacerbations favored brensocatib at both the 10 mg and 25 mg doses over placebo for almost all subgroups. In a separate analysis, least squares mean difference for brensocatib 25 mg demonstrated a reduced decline in post-bronchodilator FEV1 at Week 52 versus placebo for all prespecified subgroups. Results for patients treated with brensocatib 10 mg among subgroups were aligned with the overall trial population results. Brensocatib was well-tolerated in the study."

Late-breaking abstract • P3 data • Non‐Cystic Fibrosis Bronchiectasis

TEMPORARY REMOVAL: A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL OF BRENSOCATIB IN PATIENTS WITH NON-CYSTIC FIBROSIS BRONCHIECTASIS - THE ASPEN TRIAL. (PubMed, Chest) - "A replacement will appear as soon as possible, or the abstract will be reinstated. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/policies/article-withdrawal."

Clinical • Journal • P3 data • Bronchiectasis • Genetic Disorders • Immunology • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases

Cathepsin C exacerbates EAE by promoting the expansion of Tfh cells and the formation of TLSs in the CNS. (PubMed, Brain Behav Immun) - "Conversely, treatment with AZD7986, a specific inhibitor of CatC, effectively attenuated the syndrome of EAE and its effects caused by CatC both in vivo and in vitro. These findings provide a novel insight into the critical role of CatC in innate and adaptive immunity in EAE, and specific inhibitor of CatC, AZD7986, may contribute to potential therapeutic strategies for MS."

Journal • CNS Disorders • Immunology • Inflammation • Inflammatory Arthritis • Multiple Sclerosis • Rheumatoid Arthritis • Rheumatology • Solid Tumor • CD4 • CTSC

Insmed Reports Second-Quarter 2024 Financial Results and Provides Business Update (PRNewswire) - "Insmed looks forward to presenting additional data from the ASPEN study, including prespecified subpopulation data, at CHEST 2024, taking place October 6-9 in Boston...The Company continues to enroll patients in the Phase 2b BiRCh trial of brensocatib in patients with chronic rhinosinusitis without nasal polyps (CRSsNP) and anticipates providing topline data from the study in the second half of 2025; The Company anticipates activating the first U.S. sites in its Phase 2 study of brensocatib in patients with hidradenitis suppurativa (HS) by the end of 2024....Insmed continues to anticipate that over 80% of total expenditures will be on its mid- to late-stage and commercial programs (ARIKAYCE, brensocatib, and TPIP), and that less than 20% of overall spend will be on its early-stage research programs, reflecting the Company's historical approach to spending."

Commercial • New P2 trial • P2b data • P3 data • Trial status • Bronchiectasis • Hidradenitis Suppurativa • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases