nintedanib inhaled (AP02) / Avalyn Pharma - LARVOL DELTA

Inhaled Pirfenidone as an innovative therapeutic approach to treat autoimmune ILD and other forms of Progressive Pulmonary Fibrosis: Phase 2b Study Design (EULAR 2025) - "Patients will remain on stable background immunosuppression and up to 30% of patients will remain on background nintedanib therapy. MIST is the first study to analyze the novel concept of inhaled medications in autoimmune ILD. Safety and efficacy of AP01 in patients with PPF will be studied. In addition to the safety and efficacy endpoints, MIST will examine the presence of cough in this population of patients."

P2b data • Cough • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases

A Double-blind, Placebo-controlled, Randomized Phase 1 Study to Evaluate Safety, Tolerability, and Pharmacokinetics After Single or Repeat Twice-daily Doses of AP02, a Nebulized Formulation of Nintedanib (ATS 2025) - "AP02 was well-tolerated following single doses and throughout 7 days of twice daily doses of up to the highest dose (8 mg BID). Exposures in BALF exceeded IC50 values of target TKs and were higher than those observed following oral administration at the approved dose, suggesting establishment of clinically meaningful exposure. The safety and PK support further clinical development and suggest AP02 could offer a promising new treatment option for IPF and PPF."

Clinical • Late-breaking abstract • P1 data • PK/PD data • Cough • Immunology • Pulmonary Disease • Respiratory Diseases

Dose-Dependent Change of Inhaled Pirfenidone Seen in Lung Volume and Fibrosis Quantification in Patients With IPF: A Deep Learning Image-Based Analysis of Data From the ATLAS Phase 1b Trial (ATS 2025) - P1 | "Patients ineligible for, intolerant of, or unwilling to start oral pirfenidone or nintedanib were randomised 1:1 to receive nebulised AP01 50mg QD or 100mg BID for up to 72 weeks... Patients on the higher dose regime of 100mg AP01 showed a smaller lung volume reduction at week 36 and reduced fibrosis progression at week 24 compared to the 50mg dose. There was a trend across both time points to less fibrosis extent progression in the higher dose regime. Deep learning-based imaging biomarkers can be used to quantify dose-dependent effects on disease progression and suggest a dose-dependent effect of AP01 in patients with IPF."

Clinical • P1 data • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology

Inhaled Nintedanib (AP02) for the Treatment of IPF: Safety, Tolerability, and Pharmacokinetics After Single Ascending Doses to Healthy Subjects and IPF Patients (ATS 2025) - "AP02 was well-tolerated at single doses of up to the highest dose (2mg) and demonstrated higher BALF exposure than oral administration at the approved dose. The safety and PK support further clinical advancement and suggest that AP02 could offer a promising new treatment for IPF."

Clinical • PK/PD data • Cough • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pain

Title: Inhaled Nintedanib (AP02) for the Treatment of IPF: Safety, Tolerability, and Pharmacokinetics After Single Ascending Doses to Healthy Subjects and IPF Patients (GlobeNewswire) - P1a | N=38 | "Avalyn showcases clinical data across multiple pulmonary fibrosis programs at ATS 2025....Avalyn’s Phase 1a trial of AP02 assessed clinical tolerability and pharmacokinetic profiles in three SAD cohorts, up to a maximum 2.0 mg dose in HVs; two BAL cohorts in HVs; and one cohort of patients with IPF. AP02 was well-tolerated at all doses explored in this study....AP02 demonstrated a dose-related increase in systemic exposure. Between HVs and patients with IPF, there was no difference in systemic exposure with inhaled dosing. Notably, inhaled dosing resulted in approximately 15-fold lower Cmax and 68-fold lower AUC0-24 than the oral nintedanib approved dosage. Additionally, AP02 demonstrated approximately 9-fold higher bronchoalveolar lavage fluid (BALF) exposure than oral administration..."

P1 data • Idiopathic Pulmonary Fibrosis

Title: A Double-blind, Placebo-controlled, Randomized Phase 1 Study to Evaluate Safety, Tolerability, and Pharmacokinetics After Single or Repeat Twice-daily Doses of AP02, a Nebulized Formulation of Nintedanib (GlobeNewswire) - P1 | N=68 | ACTRN12624000825550 | Sponsor: Avalyn Pharma, Inc. | "Avalyn showcases clinical data across multiple pulmonary fibrosis programs at ATS 2025....Avalyn presented a late-breaking poster presentation on the recently completed Phase 1 trial of AP02. The study enrolled a total of 60 healthy volunteers (HVs)....AP02 was well-tolerated following single doses and 7 days of twice daily (BID) doses, up to the highest dose (8 mg BID). The most common treatment-emergent adverse events were throat irritation and dizziness, all of which were mild and mostly resolved during the study. There were no cases of bronchospasm, cough, or diarrhea observed in the study. Notably, AP02 treatment had substantially lower systemic exposures than historical data with oral nintedanib, the current standard-of-care antifibrotic therapy for patients with IPF."

P1 data • Idiopathic Pulmonary Fibrosis

Avalyn Announces Multiple Presentations on AP01 and AP02 for Pulmonary Fibrosis at the American Thoracic Society 2025 International Conference (GlobeNewswire) - "Avalyn Pharma Inc...announced multiple presentations at the American Thoracic Society (ATS) 2025 International Conference being held May 16-21, 2025, at the Moscone Center in San Francisco, CA...Avalyn’s presentations will include topline data from the single- and multiple-ascending dose Phase 1 clinical trials of AP02 (inhaled nintedanib) in healthy adult volunteers and patients with idiopathic pulmonary fibrosis (IPF) and new long-term safety and efficacy data from the ATLAS open-label extension trial of AP01 (inhaled pirfenidone) in patients with IPF and progressive pulmonary fibrosis (PPF). Furthermore, the company, in collaboration with Qureight, will present results from two deep learning-based analyses of high-resolution computed tomography (HRCT) scans and patient data from the Phase 1b ATLAS trial of AP01, exploring the utility of novel imaging biomarkers and synthetic study arms in validating treatment efficacy in patients with IPF."

Clinical data • Idiopathic Pulmonary Fibrosis

Breathing New Life: Inhaled Nintedanib and the Future of Pulmonary Fibrosis Treatment (ATS 2025) - "Join us as we explore how AP02 is poised to breathe new life into the treatment of pulmonary fibrosis. This program was developed by Avalyn Pharma and is neither sponsored by nor endorsed by ATS and does not offer CME/CE credit."

Immunology • Pulmonary Disease • Respiratory Diseases

Avalyn Completes Successful Phase 1 Clinical Trials of AP02, its Novel Inhaled Formulation of Nintedanib, Preparing for Phase 2 Development in Idiopathic Pulmonary Fibrosis (GlobeNewswire) - "Avalyn Pharma...announced that AP02 (inhaled nintedanib) was safe and well tolerated in multiple single-ascending dose (SAD) and multiple-ascending dose (MAD) Phase 1 clinical trials in healthy adult volunteers and patients with idiopathic pulmonary fibrosis (IPF)....The most recently completed Phase 1 trial enrolled a total of 60 healthy adult volunteers....The company expects to present full topline data from two Phase 1 studies, including safety, tolerability, and pharmacokinetics at the American Thoracic Society 2025 International Conference in May 2025. Based on these results, Avalyn plans to advance AP02 into a Phase 2 clinical program for patients with idiopathic pulmonary fibrosis (IPF)."

P1 data • Trial status • Idiopathic Pulmonary Fibrosis

A Phase 1 Study of AP02 (Nintedanib Solution for Inhalation) Delivered via the PARI eFlow® Nebulizer System to Evaluate the Safety, Tolerability, and Pharmacokinetics of AP02 in Healthy Volunteers (AP02-002) (ANZCTR) - P1 | N=68 | Completed | Sponsor: Avalyn Pharma, Inc. | Recruiting ➔ Completed

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

Design of a randomised controlled hybrid trial of nintedanib in patients with progressive myositis-associated interstitial lung disease. (PubMed, BMC Pulm Med) - P4 | "MINT is an innovative, hybrid trial that will evaluate the effects of nintedanib on symptoms, quality of life, and ILD progression in patients with progressive MA-ILD and provide valuable information on the utility of decentralised recruitment and remote data collection in clinical trials."

Clinical • Clinical protocol • Journal • Dermatomyositis • Fibrosis • Immunology • Interstitial Lung Disease • Myositis • Pulmonary Disease • Respiratory Diseases • Rheumatology

A Phase 1 Study of AP02 (Nintedanib Solution for Inhalation) Delivered via the PARI eFlow® Nebulizer System to Evaluate the Safety, Tolerability, and Pharmacokinetics of AP02 in Healthy Volunteers (AP02-002) (ANZCTR) - P1 | N=68 | Recruiting | Sponsor: Avalyn Pharma, Inc. | Not yet recruiting ➔ Recruiting | Initiation date: Jul 2024

Enrollment open • Trial initiation date • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

Avalyn Announces Initiation of Phase 1b Clinical Study for AP02, its Novel Inhaled Nintedanib (GlobeNewswire) - "Avalyn Pharma Inc...announced the initiation of its single-ascending dose (SAD) and multiple-ascending dose (MAD) Phase 1b clinical study evaluating the safety, tolerability, and pharmacokinetics of AP02 (inhaled nintedanib) in healthy adult volunteers....The randomized, double-blind, placebo-controlled Phase 1b study will evaluate the safety, tolerability, and pharmacokinetics of AP02 in healthy adult volunteers."

Trial status • Idiopathic Pulmonary Fibrosis • Pulmonary Disease

A Phase 1 Study of AP02 (Nintedanib Solution for Inhalation) Delivered via the PARI eFlow® Nebulizer System to Evaluate the Safety, Tolerability, and Pharmacokinetics of AP02 in Healthy Volunteers (ANZCTR) - P1 | N=68 | Not yet recruiting | Sponsor: Avalyn Pharma, Inc.

New P1 trial • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

Avalyn Presents Data from its AP01 and AP02 Inhaled Therapeutics Programs for Pulmonary Fibrosis (GlobeNewswire) - "Avalyn Pharma Inc...today announced the presentation of preclinical data that supported the completed Phase 1a trial of AP02 (inhaled nintedanib) as well as clinical data for AP01 (inhaled pirfenidone) at the 2023 Pulmonary Fibrosis Foundation (PFF) Summit at the JW Marriott Grande Lakes in Orlando, FL....Avalyn’s AP02-related poster presentation will outline findings with inhaled nintedanib in a human-predictive preclinical model. These data demonstrated that inhaled nintedanib was well-tolerated, was indicative of efficient inhaled alveolar deposition, and delivered oral-superior lung levels with reduced systemic exposure. These results further provided dose-selection guidance for the completed Phase 1a trial."

Preclinical • Trial status • Idiopathic Pulmonary Fibrosis • Pulmonary Disease • Respiratory Diseases

Avalyn Raises $175 Million in Oversubscribed Series C Financing to Advance Inhaled Pulmonary Fibrosis Programs into Later Stage Clinical Studies (GlobeNewswire) - "Avalyn Pharma Inc...announced the closing of an oversubscribed $175 million Series C financing. Avalyn plans to use the funds to continue development of its portfolio of inhalation therapies for interstitial lung disease that improve upon currently approved medications, and advance lead clinical assets, AP01 (inhaled pirfenidone) and AP02 (inhaled nintedanib), into mid-stage clinical trials."

Commercial • Fibrosis • Idiopathic Pulmonary Fibrosis • Respiratory Diseases

Avalyn Pharma Reports Results of Phase 1 Study of AP02 in Healthy Volunteers and Participants with Idiopathic Pulmonary Fibrosis (GlobeNewswire) - P1 | N=38 | Sponsor: Avalyn Pharma | "Avalyn Pharma...today reported top-line results from the company’s Phase 1 trial for AP02 (inhaled nintedanib). AP02 was generally well tolerated, with no serious adverse events (SAEs) reported among the participants who were administered AP02. 'We were especially excited to see the tolerability results of AP02 in those participants with idiopathic pulmonary fibrosis (IPF), an underserved interstitial lung disease with survival rates between 3 and 5 years from diagnosis.'"

P1 data • Idiopathic Pulmonary Fibrosis • Interstitial Lung Disease

Inhaled pirfenidone solution (AP01) for IPF: a randomised, open-label, dose-response trial. (PubMed, Thorax) - "Side effects commonly associated with oral pirfenidone in other clinical trials were less frequent with AP01. Mean FVC % predicted remained stable in the 100 mg two times per day group. Further study of AP01 is warranted."

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

IPF, promising results from an innovative phosphodiesterase 4b inhibitor [Google Translation] (OMAR) - "A Phase II study, coordinated by Professor Luca Richeldi, shows that the drug is safe and able to slow the decline in lung function....'The 'idiopathic' form of pulmonary fibrosis is the rarest, but also the most serious', explains Professor Luca Richeldi."

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