Avalyn’s Inhaled Drug Trial Offers New Hope for IPF Patients

BOSTON – March 23, 2026 – Avalyn, a clinical-stage biopharmaceutical company, has dosed the first patient in a pivotal Phase 2 clinical trial for a new therapy that could fundamentally change how a devastating lung disease is treated. The trial, named AURA, will evaluate AP02, an inhaled formulation of the established drug nintedanib, for patients with idiopathic pulmonary fibrosis (IPF).

This milestone represents a significant step toward addressing one of the biggest challenges in IPF treatment: the debilitating side effects of oral medications that often force patients to choose between quality of life and continuing a therapy that slows the progression of their fatal disease. By delivering the drug directly to the lungs, Avalyn hopes to offer a more tolerable and effective option for patients in desperate need of innovation.

The Burden of a Devastating Disease

Idiopathic pulmonary fibrosis is a relentless and incurable disease where the lungs become progressively scarred, making it harder to breathe. The prognosis is grim, with a median survival of just three to five years after diagnosis. For years, patients had no effective treatments.

Today, two oral antifibrotic drugs, nintedanib (marketed as Ofev) and pirfenidone (Esbriet), are the standard of care. While they don't cure IPF, they are proven to slow the irreversible decline in lung function, buying patients precious time. However, this benefit comes at a high cost. Oral nintedanib, in particular, is notorious for causing severe systemic side effects.

According to clinical trial data, a majority of patients taking oral nintedanib experience diarrhea, with a significant portion also suffering from nausea, vomiting, and loss of appetite. These gastrointestinal issues are not just uncomfortable; they can be so severe that they lead to dose reductions or treatment discontinuation altogether. This leaves patients and their doctors in an untenable position, abandoning a therapy known to slow a fatal disease because the side effects are unbearable.

“For too long, many patients have struggled with the challenging side effects linked to standard-of-care oral medications and often discontinue treatment, despite the serious and progressive nature of the disease,” said Joyce Lee, M.D., a steering committee member for AP02 and Professor of Medicine at the University of Colorado School of Medicine.

A Targeted Approach to Treatment

Avalyn’s strategy with AP02 is to circumvent this problem by changing the delivery route. Instead of a pill that floods the entire body with medication, AP02 is a liquid formulation of nintedanib administered as a fine mist using a high-efficiency nebulizer, the PARI eFlow®. This device uses a vibrating membrane to generate an aerosol with precisely sized particles designed to travel deep into the distal regions of the lung where the fibrotic scarring occurs.

The principle is straightforward: deliver the drug directly where it's needed and keep it away from where it causes harm. This approach aims to maximize the therapeutic concentration in the lung tissue while minimizing the amount of drug that enters the bloodstream and circulates systemically, thereby reducing side effects like diarrhea.

Encouraging data from Avalyn’s Phase 1 studies supports this hypothesis. The trials, conducted in both healthy volunteers and IPF patients, showed that AP02 was well-tolerated at all evaluated doses. Critically, the results demonstrated higher drug exposure in the lungs compared to oral dosing but with substantially lower systemic exposure. A single 4.0 mg inhaled dose, for example, resulted in over 20 times higher lung exposure than a standard 150 mg oral dose.

Most importantly for patients, the Phase 1 program reported a favorable safety profile. There was no diarrhea reported, a stark contrast to the experience with oral nintedanib. Furthermore, there were no signs of cough or bronchospasm following repeated dosing, addressing potential concerns about lung irritation from an inhaled therapy.

The AURA Trial and What's Next

The AURA Phase 2 trial is designed to rigorously test this promising approach in a larger patient population. The randomized, double-blind, placebo-controlled study will enroll approximately 160 IPF patients who are not currently on treatment. Participants will be assigned to one of two dose levels of AP02 or a placebo, administered twice daily for 12 weeks.

The primary goal of the trial is to measure the change in forced vital capacity (FVC), a key indicator of lung function, from the beginning of the study to week 12. Investigators will also assess a range of secondary endpoints, including time to disease progression, changes in lung fibrosis seen on high-resolution CT scans, and patient-reported quality of life measures.

“The initiation of our AURA Phase 2 clinical trial represents a significant step toward our goal of providing patients with pulmonary fibrosis with an urgently needed innovative treatment option that is well-tolerated and suitable for long-term use,” said Lyn Baranowski, Chief Executive Officer of Avalyn, in the company's announcement. “We look forward to working closely with patients, investigators, and the broader pulmonary fibrosis community as we advance this important program.”

Navigating a Competitive Landscape

Avalyn is not alone in the quest for better IPF therapies. The field is a hotbed of innovation, with dozens of companies exploring novel biological pathways to halt or even reverse fibrosis. Competitors are developing drugs that target different mechanisms, such as LPA1 antagonists and Hedgehog inhibitors, in the hope of finding a more effective solution than the current antifibrotics.

However, Avalyn's strategy offers a distinct and potentially more direct path to improving patient care. Rather than discovering a new drug from scratch, the company is reformulating a proven one. If AP02 can deliver the same or better lung function benefit as oral nintedanib but with a significantly improved safety profile, it could rapidly become a preferred option for both newly diagnosed patients and those who cannot tolerate the oral version.

This approach is central to Avalyn’s entire pipeline. The company is also advancing AP01, an inhaled version of the other standard-of-care drug, pirfenidone, which has shown promising long-term safety and efficacy data in its own clinical trials. Looking further ahead, Avalyn is developing AP03, a fixed-dose combination of inhaled pirfenidone and nintedanib, a pairing that is largely unfeasible in oral form due to additive toxicity. Success with AP02 could therefore validate the company’s entire lung-targeted platform and pave the way for a new generation of inhaled respiratory therapies.