Avalyn publishes Phase 1 data showing AP02's lung-targeted delivery

Avalyn Pharma has published peer-reviewed Phase 1 pharmacokinetic data for AP02, its nebulised formulation of nintedanib, showing substantially higher lung drug concentrations and markedly lower systemic exposure than the approved oral dose. The paper appeared in Respiratory Research on 21 September 2026, roughly sixteen months after topline results were first presented at the American Thoracic Society International Conference.

The Boston-based company is developing AP02 for idiopathic pulmonary fibrosis, a progressive and ultimately fatal scarring disease of the lung for which oral nintedanib and pirfenidone are currently the only approved antifibrotic options. Both existing therapies are limited in practice by gastrointestinal and systemic side effects that reduce adherence over the long treatment courses patients require.

What the data show

The publication covers two randomised Phase 1 studies. The first enrolled 32 healthy volunteers and six IPF patients receiving AP02 in single ascending doses up to 2.0 mg, alongside a four-person comparator cohort taking the approved 150 mg oral nintedanib dose. The second study assessed single and multiple ascending doses up to 8.0 mg twice daily for seven days in 60 healthy volunteers. Both studies measured plasma pharmacokinetics and, critically, bronchoalveolar lavage fluid to estimate drug concentrations at the site of fibrosis.

At a 4.0 mg dose, AP02 achieved approximately 26-fold higher predicted peak concentration and overall exposure in epithelial lining fluid relative to oral nintedanib at 150 mg. Across all multiple-dose cohorts, systemic exposure with AP02 was 10- to 56-fold lower than mean steady-state exposure for the oral regimen. No serious adverse events were reported across either study, and no treatment-related adverse event caused a patient withdrawal. The most common adverse events were headache, nausea, mild cough and dizziness.

Melissa Rhodes, Chief Operating Officer of Avalyn Pharma, said the findings "demonstrate substantially higher predicted lung exposure alongside significantly lower systemic exposure than oral nintedanib, supporting AP02's potential to improve the therapeutic profile of this important medicine."

AURA Phase 2 trial and competitive context

Based on the Phase 1 package, Avalyn advanced AP02 into AURA, a randomised, double-blind, placebo-controlled Phase 2 trial in 160 IPF patients evaluating two twice-daily doses over twelve weeks. Topline efficacy and safety data are expected in late 2027. The company reports enrolment is on track.

Avalyn's broader pipeline extends the same inhaled-repurposing logic to pirfenidone (AP01, currently in the MIST Phase 2b trial for progressive pulmonary fibrosis) and to AP03, an inhaled fixed-dose combination of both antifibrotics. The strategy is distinctive in that it does not seek to discover new molecular entities; instead it aims to improve the therapeutic index of validated compounds through a proprietary drug-device platform that concentrates drug at the target organ.

The approach faces both scientific and commercial questions. Lung delivery of small molecules via nebuliser depends heavily on patient technique and device compliance, and twice-daily nebulisation carries its own adherence burden that will need to be weighed against the tolerability gains demonstrated in Phase 1. In the broader IPF landscape, a number of companies are pursuing novel mechanisms, including autotaxin inhibitors and integrin antagonists in late-stage development, which could reframe the treatment paradigm before an inhaled nintedanib product reaches the market. Whether the Phase 2 AURA readout in late 2027 can demonstrate a clinically meaningful functional benefit, beyond the pharmacokinetic rationale established in Phase 1, will be the key inflection point for the programme.