Ep206: Lyn Baranowski on Inhalable Medicines for Severe Lung Diseases

What It Covers

Avalon Pharma CEO Lyn Baranowski explains how the company reformulates two approved oral pulmonary fibrosis drugs — pirfenidone and nintedanib — into inhaled versions delivered via handheld nebulizer, reducing doses by up to 97% while achieving 27x higher lung tissue exposure, targeting the 70% of IPF patients currently untreated due to intolerable side effects.

Key Questions Answered

• •Oral drug tolerability gap: Only 30% of the 300,000 annual U.S. pulmonary fibrosis patients are on approved oral therapies at any given time, and just 10% remain on treatment across a full year. Pirfenidone causes severe nausea and vomiting; nintedanib causes debilitating diarrhea. This leaves a calculated addressable U.S. market of $42B annually — 300,000 patients at $150,000 per patient per year — almost entirely untapped.
• •Inhaled dose reduction mechanics: Reformulating pirfenidone for inhalation drops the daily dose from 2,400mg to 200mg — a 92% reduction. Inhaled nintedanib drops from 150mg to 4mg. Despite these reductions, lung tissue drug concentrations measured via bronchoalveolar lavage show 27x higher AUC exposure than oral delivery, because the drug is deposited directly into the alveoli rather than distributed systemically.
• •Particle size as a delivery variable: Getting drugs to distal lung tissue requires generating particles in a precise size range — small enough to reach the alveoli but large enough to adhere on contact. Too small and the particles are exhaled before depositing. Avalon uses a PARI handheld nebulizer, the same device platform used by Insmed for ARIKAYCE, with exclusive rights for their specific molecules and custom drug-device combination patents.
• •Phase 1b lung function stabilization data: In the ATLAS Phase 1b study, inhaled pirfenidone produced only 0.4% annual lung function decline — equivalent to a healthy adult's normal aging loss — compared to 3% decline on oral pirfenidone and 7% decline on placebo. Some patients enrolled six years ago remain on drug with stable forced vital capacity, in a disease where median survival is three to five years post-diagnosis.
• •Inhaled drug IP moat structure: Avalon holds three layered patent protections: formulation patents (11 issued, 2 pending on APO-1), drug-device combination patents, and exclusive device licensing with PARI. Additionally, FDA requires generic nebulizer competitors to conduct large-scale clinical trials — not just bioequivalence studies — creating a regulatory barrier that makes inhaled generics substantially harder to bring to market than standard oral generics.
• •Pipeline combination rationale: APO-3, a fixed-dose inhaled combination of both pirfenidone and nintedanib, enters Phase 1 in late 2025. The mechanistic rationale draws from Boehringer Ingelheim's prior clinical work showing complementary activity between the two agents. Avalon's Phase 2b data for APO-1 and APO-2 are both expected in the second half of 2027, with single Phase 3 trials planned to follow each readout.