Avalyn completes Phase 2b MIST enrollment for inhaled pirfenidone
Avalyn Pharma has completed target enrolment of 375 patients in the MIST Phase 2b clinical trial of AP01, its inhaled formulation of pirfenidone, for progressive pulmonary fibrosis. The NASDAQ-listed company said enrolment closed ahead of schedule, with a small number of patients still in screening who may be randomised over the coming weeks.
MIST is a global, randomised, double-blind, placebo-controlled study evaluating two doses of AP01 against placebo. Patients are randomised 2:1:2 into three cohorts: AP01 100 mg twice daily, AP01 50 mg twice daily, and placebo. The primary endpoint is change from baseline in forced vital capacity at 52 weeks, a standard measure of lung function decline used across fibrosis trials.
The clinical case for an inhaled formulation
AP01 is built on pirfenidone, an established oral antifibrotic approved for idiopathic pulmonary fibrosis in both the US and EU. Avalyn's rationale is that delivering the drug directly to the lung via the PARI eRapid nebuliser system could reduce the systemic side-effect burden, particularly the gastrointestinal toxicities and liver enzyme elevations associated with oral pirfenidone, which are a recognised driver of treatment discontinuation in practice.
Phase 1b ATLAS data showed low rates of those adverse events and a suggested trend toward lung-function stability at the higher dose, though Avalyn has been careful to describe the signal as a trend rather than a confirmed effect. The ongoing open-label extension study is providing longer-term tolerability data ahead of the MIST readout.
Chief executive Lyn Baranowski said the pace of enrolment "underscores the demand for new treatment options in PPF." Tim Whelan, professor of medicine at the Medical University of South Carolina and a MIST investigator, noted that even with existing therapies, median survival after diagnosis remains three to five years.
Market context and competitive landscape
Progressive pulmonary fibrosis covers a heterogeneous group of patients whose lung disease worsens despite treatment, including those with connective tissue disease-associated ILD and other non-IPF fibrosing conditions. The PPF label has attracted growing regulatory and commercial attention following the approval of nintedanib for that broader population by the FDA in 2020.
Avalyn is itself developing AP02, an inhaled formulation of nintedanib, in a separate Phase 2 trial in IPF, and is advancing AP03, a fixed-dose inhaled combination of pirfenidone and nintedanib. That pipeline positions the company as a lung-targeted antifibrotic platform rather than a single-asset bet, which may be relevant to future partnering conversations.
The PPF space remains competitive. Established players with approved systemic antifibrotics hold significant market share, and a number of companies are investigating novel mechanisms, including LOXL2 inhibitors, integrin antagonists, and autotaxin inhibitors, in late-stage development. Avalyn's differentiation rests on tolerability and adherence rather than a novel target, a credible but commercially harder argument to make without head-to-head data.
Topline results from MIST are expected in the second half of 2027. Investors will look for the FVC trajectory at 52 weeks and, critically, the safety profile relative to historical oral pirfenidone benchmarks. A positive readout would set up an end-of-Phase 2 meeting with the FDA and likely trigger a Series C or partnership discussion.