Airway Therapeutics announced that the European Medicines Agency (EMA) Pediatric Committee (PDCO) has approved its Pediatric Investigation Plan (PIP) for zelpultide alfa, marking a significant regulatory milestone for the first-in-class recombinant human surfactant protein D (rhSP-D) therapy designed to prevent bronchopulmonary dysplasia (BPD) in very preterm infants born between 22 and 27 weeks gestational age.
The clinical-stage biopharmaceutical company's investigational biologic represents a novel therapeutic approach for a vulnerable patient population with no currently approved preventative treatments. Zelpultide alfa is engineered to modulate immune responses to reduce inflammation, enhance pathogen clearance, and support surfactant homeostasis for improved lung function.
Pivotal Trial Design and Timeline
The approved PIP outlines a comprehensive Phase 2b/3 clinical trial structure. The Phase 2b portion will evaluate two different dose levels of zelpultide alfa administered for up to seven days, compared to placebo, across 150 patients with 50 patients per arm. Following treatment completion, investigators will select one dose for continuation into Phase 3, which will enroll approximately 216 additional patients.
"We are pleased to have reached agreement with the PDCO on the Pediatric Investigation Plan and pivotal study design for zelpultide alfa, a ground-breaking therapy being developed to prevent BPD in very preterm infants, a highly vulnerable population with no approved preventative treatments," said Dr. Marc Salzberg, Chairman, Chief Executive & Medical Officer of Airway Therapeutics.
The study incorporates a three-day consecutive BPD evaluation endpoint, which may contribute to developing improved outcome measures during the trials. Airway Therapeutics plans to initiate the clinical trial in late Q3 or Q4 2025, with immediate protocol submissions to health authorities in Italy (AIFA), Spain (AEMPS), and Israel (MoH).
Addressing Critical Unmet Medical Need
Bronchopulmonary dysplasia remains one of the most significant challenges in neonatal intensive care, with long-term implications extending beyond respiratory function to neurodevelopmental outcomes. The condition affects very preterm infants and currently lacks approved preventative interventions.
"Bronchopulmonary dysplasia remains one of the most challenging complications in neonatal intensive care, with long-term consequences for respiratory and neurodevelopmental outcomes," said Dr. Daniele De Luca, Principal Investigator of the trial and Professor of Pediatrics (Neonatology) at Paris Saclay University. "Zelpultide alfa represents a novel and scientifically promising approach, grounded in our understanding of immune modulation and tissue injury."
Therapeutic Mechanism and Platform Potential
Zelpultide alfa is precisely engineered to replicate the native protein's full quaternary structure and biological function, incorporating optimized glycosylation through advanced cell line technology. The therapy operates through three key mechanisms: immune response modulation to mitigate excessive inflammation, enhancement of pathogen recognition and clearance, and maintenance of surfactant homeostasis to support pulmonary function.
As a versatile biologic platform, zelpultide alfa is being developed for patients across all age groups, from preventing BPD in very preterm infants to treating acute and chronic respiratory, inflammatory, and infectious conditions in adults. The therapy has demonstrated a favorable safety and tolerability profile in Phase 1 studies.
Global Regulatory Strategy
Following the initial submissions to Italy, Spain, and Israel, Airway Therapeutics plans additional regulatory filings in France, Germany, Belgium, and Poland, along with planned submissions in Argentina, Australia, and the United States. This multinational approach reflects the global need for effective BPD prevention strategies in neonatal care.
Dr. Salzberg emphasized the milestone's significance: "This marks a significant milestone in advancing a potential first-in-class preventive therapy to improve outcomes for these fragile infants and address a critical unmet medical need."
