verducatib (BI 1291583) / Boehringer Ingelheim - LARVOL DELTA

Bronchiectasis Treatment Goals, Unmet Needs, and Emerging Therapies: A Podcast. (PubMed, Pulm Ther) - "In the phase 3, 52-week ASPEN trial, brensocatib significantly reduced exacerbation burden, and the 25-mg dose reduced lung function decline and nominally significantly improved patient-reported symptoms compared with placebo. Additional therapies in development include other DPP1 inhibitors (verducatib and HSK31858) and drugs targeting phosphodiesterase 3/4 inhibition (ensifentrine) and anti-interleukin-33 (itepekimab). Overall, the future is promising for patients with the historically neglected and underdiagnosed disease bronchiectasis, with growing awareness and new therapeutic tools becoming available. Podcast (MP4 81554 KB)."

Journal • Bronchiectasis • Genetic Disorders • Immunology • Infectious Disease • Inflammation • Non‐Cystic Fibrosis Bronchiectasis • Pediatrics • Pulmonary Disease • Respiratory Diseases • IL33

The AIRTIVITY™ Study: A Study to Find Out Whether BI 1291583 Helps People With Bronchiectasis (clinicaltrials.gov) - P3 | N=1755 | Recruiting | Sponsor: Boehringer Ingelheim | Trial completion date: Aug 2027 ➔ Oct 2028 | Trial primary completion date: Jul 2027 ➔ Sep 2028

Trial completion date • Trial primary completion date • Bronchiectasis • Pulmonary Disease • Respiratory Diseases

The AIRTIVITY™ Study: A Study to Find Out Whether BI 1291583 Helps People With Bronchiectasis (clinicaltrials.gov) - P3 | N=1755 | Recruiting | Sponsor: Boehringer Ingelheim | Trial completion date: Oct 2028 ➔ Aug 2027 | Trial primary completion date: Sep 2028 ➔ Jul 2027

Trial completion date • Trial primary completion date • Bronchiectasis • Pulmonary Disease • Respiratory Diseases

A Phase II study (CLAIRAFLY®) evaluating safety, tolerability, pharmacokinetics and pharmacodynamics of the DPP1 (CatC) inhibitor BI 1291583 in cystic fibrosis: Effects of CFTR modulator therapy use (NACFC 2025) - P2 | " Of the 22 participants randomized, 50.0% had stable CFTRmt use at baseline (9 participants (40.9%) on elexacaftor/ivacaftor/tezacaftor). This study suggests that CFTRmt use has no effect on the BI 1291583 safety profile or PK. Sputum NE activity was reduced for people with CFBE with or without CFTRmt, with a potential for greater effect relative to baseline in people on CFTRmt. Interestingly, in this population with a history of PExs, baseline sputum NE activity was similar regardless of CFTRmt use, with both groups having similar levels to those seen in AIRLEAF®."

Clinical • P2 data • PK/PD data • Bronchiectasis • Cystic Fibrosis • Dental Disorders • Genetic Disorders • Immunology • Inflammation • Non‐Cystic Fibrosis Bronchiectasis • Periodontitis • Pulmonary Disease • Respiratory Diseases • CFTR • CTSC • ELANE

A Phase II study (CLAIRAFLY®) to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of the dipeptidyl peptidase 1 (cathepsin C) inhibitor BI 1291583 in adults with cystic fibrosis bronchiectasis (WBC 2025) - P2 | "The safety, tolerability, PK and PD of BI 1291583 were similar in both CLAIRAFLY® and AIRLEAF®. These findings support the inclusion of both people with CFBE and non–CFBE in the Phase III AIRTIVITY® study."

Clinical • P2 data • PK/PD data • Bronchiectasis • Cystic Fibrosis • Genetic Disorders • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • CTSC • ELANE

Study design of a Phase III study (AIRTIVITY®) of the novel dipeptidyl peptidase 1 (cathepsin C) inhibitor BI 1291583 in people with bronchiectasis (WBC 2025) - "AIRTIVITY® intends to further evaluate evidence for the efficacy, safety and tolerability of BI 1291583 2.5mg in a large and broad population of people with bronchiectasis. AIRTIVITY® is due to begin in Q2 2025."

P3 data • Asthma • Bronchiectasis • Chronic Obstructive Pulmonary Disease • Cystic Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Inflammation • Pulmonary Disease • Respiratory Diseases • CTSC

Results from a Phase II study (AIRLEAF®) of the dipeptidyl peptidase 1 (cathepsin C) inhibitor BI 1291583 in adults with bronchiectasis (WBC 2025) - "Results from AIRLEAF® show that the DPP1 inhibitor BI 1291583 at a dose of 2.5mg and 5mg reduced the risk of experiencing a PEx in adults with bronchiectasis, while demonstrating a similar safety profile to placebo. These results support the continued clinical development of BI 1291583, with the 2.5mg dose to be assessed in the Phase III AIRTIVITY® study that is planned to begin in Q2 2025."

Clinical • P2 data • Bronchiectasis • Infectious Disease • Inflammation • Pulmonary Disease • Respiratory Diseases • CTSC

A Phase II study (CLAIRAFLY®) to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of the dipeptidyl peptidase 1 (cathepsin C) inhibitor BI 1291583 in adults with cystic fibrosis bronchiectasis (WBC 2025) - P2 | "The safety, tolerability, PK and PD of BI 1291583 were similar in both CLAIRAFLY® and AIRLEAF®. These findings support the inclusion of both people with CFBE and non–CFBE in the Phase III AIRTIVITY® study."

Clinical • Late-breaking abstract • P2 data • PK/PD data • Bronchiectasis • Cystic Fibrosis • Genetic Disorders • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • CTSC • ELANE

Study designs of three Phase II trials of the novel cathepsin C inhibitor BI 1291583 in patients with bronchiectasis (WBC 2024) - P2 | "These trials will provide information on the safety and efficacy of BI 1291583 in patients with bronchiectasis and inform the design of Phase III trials."

Clinical • P2 data • Bronchiectasis • Cystic Fibrosis • Genetic Disorders • Immunology • Inflammation • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases • CTSC • ELANE

A phase III study (AIRTIVITY®) to assess the efficacy, safety and tolerability of the DPP1 (CatC) inhibitor BI 1291583 in adults and adolescents with bronchiectasis of various etiologies (NACFC 2025) - "Based on the promising Phase II AIRLEAF® results, AIRTIVITY® will assess the efficacy of BI 1291583 2.5 mg. The adolescent-specific endpoints examined in this study may support future development of BI 1291583 in younger people with BE. AIRTIVITY® is due to begin in Q2 2025, with the first adolescent planned to be screened in Q4 2025."

Clinical • P3 data • Bronchiectasis • Inflammation • Pediatrics • Pulmonary Disease • Respiratory Diseases • CTSC

Neutrophil elastase activity following cathepsin C (CatC, or DPP1) inhibition with BI 1291583 in people with bronchiectasis (ERS 2025) - "1 Chalmers JD, et al. Eur Respir J 2025; 65:2401551"

Bronchiectasis • Pulmonary Disease • Respiratory Diseases • CTSC • ELANE

Pooled data from Phase II studies (AIRLEAF®, CLAIRLEAF®) of the cathepsin C (CatC, or DPP1) inhibitor BI 1291583 in bronchiectasis (ERS 2025) - "1 Chalmers JD et al. Eur Respir J 2025; 65:2401551"

P2 data • Bronchiectasis • Pulmonary Disease • Respiratory Diseases • CTSC

Subgroup analysis: AIRLEAF® Phase II study of a cathepsin C (CatC, or DPP1) inhibitor, BI 1291583, in adults with non–cystic fibrosis bronchiectasis (ERS 2025) - "Eur Respir J 2025; 65:2401551 Table 1. Subgroup analyses of risk and rate of PExs up to 48 weeks in the 2.5 mg dose group vs placebo"

Clinical • P2 data • Bronchiectasis • Cystic Fibrosis • Genetic Disorders • Immunology • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases • CTSC

A Study in Healthy People to Test Whether Erythromycin Influences the Amount of BI 1291583 in the Blood (clinicaltrials.gov) - P1 | N=20 | Completed | Sponsor: Boehringer Ingelheim | Active, not recruiting ➔ Completed

Trial completion

Dipeptidyl peptidase 1 inhibitors for inflammatory respiratory diseases: mechanisms, clinical trials, and therapeutic prospects. (PubMed, Front Pharmacol) - "Leading compounds including brensocatib, BI 1291583, and HSK31858 have demonstrated substantial clinical efficacy. Future research priorities include establishing standardized monitoring protocols for dermatological and periodontal health, developing biomarkers for patient stratification, validating long-term safety profiles, and optimizing combination treatment strategies. With brensocatib potentially becoming the first approved mechanism-specific therapy for bronchiectasis by mid-2025, DPP1 inhibitors represent a paradigm shift in managing neutrophil-mediated respiratory diseases."

Journal • Review • Bronchiectasis • Chronic Obstructive Pulmonary Disease • Genetic Disorders • Immunology • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases

Dipeptidyl peptidase 1 inhibitors and neutrophilic inflammation in bronchiectasis: a narrative review. (PubMed, J Thorac Dis) - "Of these, brensocatib markedly prolonged the time to the first exacerbation and decreased the exacerbation frequency via decreasing the activity of NSPs...Treatment with BI 1291583 reduced the risk of bronchiectasis exacerbations in the phase II Airleaf® trial. HSK31858 significantly decreased the exacerbation frequency and prolonged the time to the first exacerbation in the latest phase II trial among the Chinese population. DPP-1 inhibitors have exhibited promising effects in improving several major clinical outcomes in bronchiectasis via suppressing the activity of NSPs."

Journal • Review • Bronchiectasis • Infectious Disease • Inflammation • Pulmonary Disease • Respiratory Diseases • CTSC • ELANE

A Study to Test How BI 1291583 is Taken up in the Blood of People With and Without Liver Problems (clinicaltrials.gov) - P1 | N=32 | Recruiting | Sponsor: Boehringer Ingelheim | Not yet recruiting ➔ Recruiting

Enrollment open • Hepatology

A Study in Healthy People to Test Whether Erythromycin Influences the Amount of BI 1291583 in the Blood (clinicaltrials.gov) - P1 | N=20 | Active, not recruiting | Sponsor: Boehringer Ingelheim | Recruiting ➔ Active, not recruiting

Enrollment closed

The AIRTIVITY® Study: A Study to Find Out Whether BI 1291583 Helps People With Bronchiectasis (clinicaltrials.gov) - P3 | N=1680 | Recruiting | Sponsor: Boehringer Ingelheim | Not yet recruiting ➔ Recruiting

Enrollment open • Bronchiectasis • Pulmonary Disease • Respiratory Diseases

A Study to Test How BI 1291583 is Taken up in the Blood of People With and Without Liver Problems (clinicaltrials.gov) - P1 | N=32 | Not yet recruiting | Sponsor: Boehringer Ingelheim

New P1 trial • Hepatology

A Phase II trial (CLAIRAFLY) to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of the dipeptidyl peptidase 1 inhibitor BI 1291583 in adults with bronchiectasis due to cystic fibrosis (ECFS 2025) - P2 | "These data support a One BE approach, in which patients with CFBE and NCFBE are included in the Ph 3 AIRTIVITY trial."

Clinical • P2 data • PK/PD data • Bronchiectasis • Cystic Fibrosis • Genetic Disorders • Immunology • Inflammation • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases • CTSC • ELANE

Study Design of a Phase III Study (AIRTIVITY®) of the Novel Cathepsin C (Dipeptidyl Peptidase 1) Inhibitor BI 1291583 in People With Bronchiectasis (ATS 2025) - "AIRTIVITY® is due to begin in 2025. [asterisk]This abstract has been developed from a draft protocol and therefore some aspects are yet to be confirmed."

P3 data • Bronchiectasis • Infectious Disease • Inflammation • Pulmonary Disease • Respiratory Diseases • CTSC

A Study in Healthy People to Test Whether Erythromycin Influences the Amount of BI 1291583 in the Blood (clinicaltrials.gov) - P1 | N=16 | Recruiting | Sponsor: Boehringer Ingelheim | Not yet recruiting ➔ Recruiting

Enrollment open

A Study in Healthy People to Test How 2 Different Doses of BI 1291583 Are Taken up in the Body When Given in 3 Different Formulations (clinicaltrials.gov) - P1 | N=30 | Completed | Sponsor: Boehringer Ingelheim | Active, not recruiting ➔ Completed

Trial completion

A Study in Healthy People to Test Whether Erythromycin Influences the Amount of BI 1291583 in the Blood (clinicaltrials.gov) - P1 | N=16 | Not yet recruiting | Sponsor: Boehringer Ingelheim

New P1 trial