The story behind the development of ThyrOxy, ‘hormone replacement for the lung.’

Herald Therapeutics, Inc. is a founder-led biopharmaceutical company dedicated to developing a novel thyroid hormone therapy for the treatment of Acute Respiratory Distress Syndrome (ARDS) and other cardiopulmonary indications, including Infant Respiratory Distress Syndrome (IRDS) and Acute Congestive Heart Failure (CHF).

David Ingbar, MD, a pulmonologist-intensivist and translational physician-scientist, became interested in the thyroid-lung connection in the 1980s when asked to contribute chapters to the definitive text, The Thyroid, now in its 11th edition. Building on his interest in the alveolar epithelium, respiratory failure, and speeding lung repair, he discovered that the thyroid hormone T3 rapidly speeds resorption of pulmonary edema fluid in normal and damaged lungs—acting via a non-transcriptional mechanism with two distinct kinase pathways. His lab later discovered that T3 also protects against oxidative lung injury and reduces lung inflammation. He is a Professor of Medicine, Pediatrics and Integrative Biology & Physiology at the University of Minnesota. Dr. Ingbar served for more than 20 years as Director of the UMN Pulmonary, Allergy & Critical Care Division. He led projects in a NIH-funded ARDS Specialized Center of Research for 10 years, served as a President of the American Thoracic Society, and has been a member of both the NHLBI Advisory Council and the ABIM Pulmonary Board.

Timothy Rich, MD, a pulmonologist-intensivist, physician-scientist, and translational researcher, first recognized the connection between thyroid and lung biology during residency. In fellowship, he joined Dr. Ingbar to potentially improve treatments for ARDS based on his patient care experiences. More specifically, Tim sought to bring bench-top discoveries to the bedside to treat ARDS, given the persistent high mortality and lack of other approved therapies. In autopsy studies of patients dying with or without ARDS, Dr. Rich demonstrated that human ARDS lungs are depleted in the essential thyroid hormone (T3), due to rapid T3 destruction by increased levels of the inactivating enzyme Deiodinase 3 (DIO3, D3). This discovery advanced the rationale for thyroid hormone replacement for the lung.

Robert Schumacher, PhD, joined the team to help translate David and Tim’s discoveries into a breakthrough therapy for ARDS. After realizing existing T3 formulations were not safe for the lungs, Bob developed ThyrOxy—a novel formulation specifically designed for direct, effective delivery into lung airways and airspaces. He then directed the preclinical safety and toxicology work that secured FDA approval for ThyrOxy’s first-in-human clinical trials. Since then, Bob has led the development of additional T3 formulations and compounds, significantly expanding the potential for lung-directed T3 therapies to treat a wide range of conditions beyond ARDS.