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The Long Run with Luke Timmerman

Ep206: Lyn Baranowski on Inhalable Medicines for Severe Lung Diseases

67 min episode · 3 min read
·
Lyn Baranowski

Episode

67 min

Read time

3 min

Topics

Productivity, Health & Wellness, Remote Work

AI-Generated Summary

Key Takeaways

  • 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.

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.

Notable Moment

Baranowski describes patients in Avalon's open-label extension who were diagnosed with pulmonary fibrosis eight years ago and remain alive with stable lung function — in a disease where median survival is three to five years. She notes no comparable long-term survival data exists for either approved oral therapy, making this an unprecedented clinical observation.

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Episode Transcript

Welcome to the Long Run. This is a podcast for biotech adventurers. I'm your host, Luke Timmerman. Today's guest is Lynn Baranowski. Lynn is the CEO of Boston based, Avalon Pharma. The company is developing inhalable drugs for rare and severe lung diseases, such as pulmonary fibrosis and other interstitial lung diseases. Avolene has started with a couple of small molecules that are given orally and remade them into inhalable drugs so they can be more effectively delivered where they need to go, deep in the lungs. By concentrating delivery, the idea is that Avalon will be able to lower the doses needed and make treatments that are easier for patients to tolerate over the long term. In this episode, you'll hear Lynn's enthusiasm for developing better treatments for respiratory diseases. It's one of these therapeutic areas that doesn't capture a lot of news coverage, but lung diseases of one kind or another really affect many millions of people. Now before we get started, a word from the sponsor of the show, AlphaSense. Under unprecedented time and cost pressures, many life sciences teams have reached for off the shelf AI tools to stay afloat. Yet they have discovered that generic AI tools introduce new risks, such as hallucination. Tools that cannot withstand scientific or regulatory scrutiny are a liability in MLR review, portfolio committees, and investment decisions where every claim must be traceable to a source. More than isolated tools, teams need a purpose built intelligence layer designed for the rigor that the industry demands. Across life sciences functions, platforms like AlphaSense are streamlining the entire decision cycle. Go to timbermanreport.com for a link to download a report that covers the top AI use cases that have transformed how the industry's leading teams reach defensible answers. And quick question, when was the last time a CRO told you what something costs before you sign an NDA, sat through two scoping calls, and waited a week for a scope of work? In bioanalysis, pricing gets treated like a closely guarded secret. Dashbio thinks that's backward. It publishes pricing publicly on its website and even has a calculator that shows how the price changes if you redesign your study. You can see what your study costs before you talk to a human being. No surprise line items, no it depends, no games. Dash was built to be the bioanalysis company that's actually straightforward to work with, transparent pricing, guaranteed timelines, and data in days, not months. If you're tired of pricing that feels like a negotiation every single time, run your bioanalysis with Dash. Visit -.bio/pricing and see exactly how much your next bioanalysis study will cost. Now please enjoy this conversation with Lynn Baranowski on the long run. Lynn Baranowski, welcome to the long run. Hi, Luke. So happy to be here. Thanks for the invitation. Well, thanks for joining me today, Lynn. I'm I'm eager to get into this with you about respiratory drug development. And, you know, it all …

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Books, tools, and gear mentioned in this episode

SignalCast may earn commission on purchases via these links. As an Amazon Associate, SignalCast earns from qualifying purchases.

Gear

  • by PARI

    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.

Products

  • by Insmed

    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.

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