nintedanib inhaled (AP02) / Avalyn Pharma - LARVOL DELTA

Avalyn Publishes Phase 1 Data Highlighting AP02’s Lung-Targeted Delivery and Encouraging Safety Profile (The Manila Times) - "AP02 was generally well tolerated across both Phase 1 studies, with no serious adverse events reported...In all of the cohorts receiving multiple ascending doses, AP02 resulted in 10- to 56-fold lower systemic exposure than the mean steady-state exposure associated with the approved 150 mg BID oral nintedanib dose. Nintedanib systemic exposure generally increased with increasing AP02 dose; Lung exposure was substantially higher with AP02 than with oral nintedanib. At a 4.0 mg dose, AP02 achieved approximately 26-fold higher predicted nintedanib peak concentration (Cmax) and overall exposure (AUC0-12) in epithelial lining fluid versus oral nintedanib dosed at 150mg...Based on these data, Avalyn advanced AP02 into the AURA clinical trial....The 12-week study is designed to enroll 160 patients to assess safety and efficacy; topline data are anticipated in late 2027."

P1 data • P2 data • Idiopathic Pulmonary Fibrosis

Nebulized pirfenidone (AP01) for progressive pulmonary fibrosis in connective tissue disease-associated and other interstitial lung diseases: 4-year data from the ATLAS open label extension trial (EULAR 2026) - P1/2, P2 | "Of the full PPF cohort, 3 (10.7%) were on background nintedanib. Despite limitations in assessing efficacy outcomes from this study, AP01 showed a favourable FVC trajectory among patients with PPF. AP01 is now being studied in the MIST study (NCT06329401), a phase 2b, randomised, placebo-controlled trial for patients with PPF, with study completion expected in 2027."

Clinical • Gastroenterology • Gastrointestinal Disorder • Idiopathic Pulmonary Fibrosis • Immunology • Infectious Disease • Inflammatory Arthritis • Interstitial Lung Disease • Pneumonia • Pulmonary Disease • Rare Diseases • Respiratory Diseases • Rheumatoid Arthritis • Rheumatology • Scleroderma • Sjogren's Syndrome • Systemic Sclerosis

AURA-IPF: A Randomized Phase 2 Study to Evaluate the Safety and Efficacy of AP02 (Nintedanib Solution) in IPF (clinicaltrials.gov) - P2 | N=160 | Recruiting | Sponsor: Avalyn Pharma Inc. | N=96 ➔ 160

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

AURA-IPF: A Randomized Phase 2 Study to Evaluate the Safety and Efficacy of AP02 (Nintedanib Solution) in IPF (clinicaltrials.gov) - P2 | N=96 | Recruiting | Sponsor: Avalyn Pharma Inc. | N=64 ➔ 96

Enrollment change • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

AURA-IPF: A Randomized Phase 2 Study to Evaluate the Safety and Efficacy of AP02 (Nintedanib Solution) in IPF (clinicaltrials.gov) - P2 | N=160 | Recruiting | Sponsor: Avalyn Pharma Inc. | Not yet recruiting ➔ Recruiting | N=64 ➔ 160

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

AURA-IPF: A Randomized Phase 2 Study to Evaluate the Safety and Efficacy of AP02 (Nintedanib Solution) in IPF (clinicaltrials.gov) - P2 | N=64 | Not yet recruiting | Sponsor: Avalyn Pharma Inc.

New P2 trial • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

AP02-003: AURA-IPF: A Randomized Phase 2 Study to evaluate the safety and efficacy of AP02 (nintedanib solution) in IPF (clinicaltrialsregister.eu) - P1/2 | N=32 | Not yet recruiting | Sponsor: Avalyn Pharma Inc.

New P1/2 trial • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

Avalyn Announces First Patient Dosed in AURA Phase 2 Clinical Trial Evaluating AP02, Inhaled Nintedanib, for the Treatment of Idiopathic Pulmonary Fibrosis (GlobeNewswire) - "The randomized, double-blind, placebo-controlled AURA Phase 2 clinical trial will evaluate the safety and efficacy of AP02 in patients with IPF. The trial is expected to enroll 160 patients with IPF, who are not currently on treatment, and will evaluate two dose levels of AP02 compared to placebo."

Trial status • Idiopathic Pulmonary Fibrosis

Inhaled pirfenidone as an innovative therapeutic approach to treat autoimmune ILD and other forms of Progressive Pulmonary Fibrosis: Phase 2b Study Design (ACR Convergence 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. 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

Avalyn Announces Multiple Presentations at the Pulmonary Fibrosis Foundation (PFF) Summit 2025 (GlobeNewswire) - "Presentations to Highlight Patient Experience Research, AURA-IPF Phase 2 Trial Design for AP02, and Long-Term Safety Data for AP01."

Clinical protocol • P2b data • Idiopathic Pulmonary Fibrosis

Avalyn Pharma Secures $100 Million in Series D Funding, Pioneering Pulmonary Fibrosis Treatment with Inhalation Therapy (36Kr) - "The funds from this round will primarily support Avalyn's key clinical progress in the field of pulmonary fibrosis treatment. This includes advancing the global Phase IIb clinical trial of its core candidate drug AP01 (inhaled pirfenidone), the late-stage development of AP02 (inhaled nintedanib), and the entry of AP03 (pirfenidone/nintedanib fixed-dose combination) into the Phase I clinical stage."

Commercial • Idiopathic Pulmonary Fibrosis • Interstitial Lung Disease • Systemic Sclerosis

AURA-IPF: A Randomized Phase 2 Study to Evaluate the Safety and Efficacy of AP02 (Nintedanib Solution) in IPF (clinicaltrials.gov) - P2 | N=160 | Not yet recruiting | Sponsor: Avalyn Pharma Inc.

New P2 trial • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

Avalyn to Highlight AURA-IPF Phase 2 Clinical Trial Design for AP02, Inhaled Nintedanib, at the European Respiratory Society International Congress 2025 (GlobeNewswire)

Clinical protocol • New P2 trial • Idiopathic Pulmonary Fibrosis

Avalyn Completes Oversubscribed $100 Million Series D Financing to Further Advance Clinical Development of Novel Inhaled Therapies for Pulmonary Fibrosis (GlobeNewswire) - "Avalyn Pharma Inc...announced the closing of an oversubscribed $100 million Series D financing...Proceeds will support key clinical milestones across Avalyn’s pipeline programs in pulmonary fibrosis, including the late-stage development of Avalyn’s lead programs: optimized inhaled formulations of pirfenidone (AP01) and nintedanib (AP02), as well as the advancement of the pirfenidone/nintedanib fixed dose combination (AP03) into Phase 1 clinical trials....The company plans to initiate a Phase 2 clinical trial for AP02 in patients with IPF."

Financing • New P2 trial • Idiopathic Pulmonary Fibrosis

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