Scratching the Surface with a Novel Approach to Treating an Orphan Lung Disease

Episode Summary

Executive Summary: This episode centers on Airway Therapeutics’ effort to develop Zeppeltide Alpha, a recombinant human surfactant protein D replacement therapy, starting with bronchopulmonary dysplasia (BPD) in premature infants. CEO Mark Salzberg explains BPD’s injury-inflammation-infection cycle, the lack of approved treatments, early safety data, and the company’s broader ambition to address other inflammatory lung diseases with a platform approach.

Main Topics: What BPD is and why it matters (Priority: 5/5): BPD is presented as a severe lung disease of preterm infants caused by ventilation- and oxygen-related lung injury that triggers inflammation and infection, impairing lung development and causing lasting respiratory and neurodevelopmental harm. Current diagnostic and treatment gap (Priority: 5/5): Diagnosis is based on oxygen/ventilation needs at 36 weeks post-menstrual age, but there is no approved prevention or treatment; current care relies on imperfect supportive measures such as caffeine, vitamin A, and steroids. Zeppeltide Alpha and surfactant protein D biology (Priority: 5/5): The company’s drug is a recombinant human surfactant protein D intended to replace a deficient innate immune protein, reduce inflammation, bind microbes, and support surfactant recycling. Why BPD is the lead indication (Priority: 4/5): BPD is chosen first because it has high unmet need, a clear biological rationale, and potential for prophylaxis that could prevent irreversible underdevelopment of the lung in the most vulnerable babies. Clinical development status and trial plans (Priority: 4/5): Airway Therapeutics reports favorable nonclinical and phase 1 safety/tolerability data and is moving into a pivotal randomized study in very preterm infants, with placebo control and dose selection. Pipeline and commercialization strategy (Priority: 4/5): Salzberg frames the program as a platform with potential in ARDS, COVID, asthma, COPD, and pneumonia, while suggesting BPD could be commercialized directly and later indications may require partnerships. Company background and financing (Priority: 3/5): Airway Therapeutics emerged from Cincinnati Children’s surfactant protein D research, has raised $100 million to date, and is seeking additional capital for pivotal development, manufacturing scale-up, and future indications.

Key Arguments: BPD results from a vicious cycle of lung injury, inflammation, secondary infection, and escalating respiratory support, making early intervention crucial. There is no registered prevention or treatment for BPD today, creating a major unmet medical need. Surfactant protein D is distinct from surfactant proteins B and C because its main role is immune modulation rather than reducing alveolar surface tension. Zeppeltide Alpha is intended as a true replacement therapy, analogous to insulin replacement in diabetes. Starting with BPD is strategically justified because the disease is devastating, untreatable, and may be preventable before irreversible lung developmental arrest occurs. Early nonclinical and phase 1 data support safety and tolerability, and the company saw promising efficacy signals worth testing in a pivotal trial. The therapy could be developed as a broader platform for inflammatory and infectious lung diseases because the mechanism is not disease-specific. Airway Therapeutics believes it could commercialize BPD itself due to the concentrated specialist hospital base, while partnering for larger adult indications and global expansion.

Data Points: Company founding: 2011 - Airway Therapeutics is described as a 2011 spinout from Cincinnati Children’s Hospital Medical Center. BPD diagnostic age: Week 36 post-menstrual age - BPD is defined clinically by the need for ventilation and oxygenation at 36 weeks post-menstrual age. Example gestational age: Week 26 birth, diagnosed 14 weeks later - Illustrates how BPD is assessed after prolonged postnatal respiratory support. Trial population age range: 22 to just below 28 weeks - Planned pivotal study in very preterm infants at high risk for BPD. Study size: About 300 to 320 patients - Randomized pivotal trial with dose-finding and placebo control. Capital raised to date: $100 million - Funding already secured for current development efforts. US hospital footprint: About 300 hospitals - Estimated number of centers that treat roughly 70% of the high-risk infant population, supporting a focused launch strategy. Patient coverage: 70% - Proportion of patient population covered by approximately 300 US hospitals.

Pivotal Quotes: "there is no registered prevention or treatment for BPD available" — Mark Salzberg: Explaining the current unmet need and why the company sees an opportunity. "we believe salpodalpha to be the first drug on the market for BPD ever, and that would be a paradigm shift" — Mark Salzberg: Discussing the significance of successful pivotal trial results. "It's essentially a replacement therapy. You can think of it like producing insulin for patients with diabetes" — Mark Salzberg: Describing how Zeppeltide Alpha is intended to function biologically.

Implications: If successful, Zeppeltide Alpha could become the first approved BPD therapy and open a new platform for surfactant protein D-based treatment of lung inflammation and infection. The broader impact could extend to neonatal care and adult respiratory disease development.