A. Pilon
APCBio Innovations, Inc. & Trove Therapeutics, Inc.,
United States
Keywords: therapeutic, homeostasis, respiratory virus, infection, acute lung injury, chemical exposure, radiation exposure
Summary:
Therabron is a new therapeutic based on recombinant human CC10 protein which has the potential to revolutionize the management of respiratory conditions, including acute lung injuries, severe influenza-like illness, inhalational injuries, and chronic lung diseases like COPD, asthma, and pulmonary fibrosis. Therabron maintains homeostasis through multiple mechanisms and targets host responses, not individual pathogens or insults, so it is a “one treatment, multiple threat” agent. It is also a dual use agent. On the commercial side, it is being developed to prevent and treat ARDS, severe influenza-like illness, chronic sinusitis, severe allergy, lung transplant rejection, asthma, and COPD. It has demonstrated proof-of-concept in multiple species with respect to controlling inflammation and lung damage, decreasing pneumonia and shock, promoting clearance of pathogens such as influenza, respiratory syncytial virus, beta coronavirus, mycobacteria, accelerating lung repair after chemical exposures, and as a post-exposure prophylaxis against radiomimetic, bleomycin, to prevent fibrosis. Therabron is not yet approved by FDA. However, it was safe and well-tolerated in 3 human clinical trials [] and in several GLP toxicology studies. It is manufactured under GMP using a bacterial expression system in a bioprocess that is robust and economical. Formulated for intravenous, intranasal, and inhaled administration, Therabron is stable over many years, even at room temperature. Therabron could improve survival in acute and chronic lung injuries caused by various toxic inhalational exposures such as burn pit exposure, smoke inhalation, and occupational or accidental chemical exposures, as well as infectious, ionizing radiation, and immunologic injuries. It has the potential to reduce patient requirements for other medical support (time in hospital, time on oxygen, etc.), facilitate respiratory rehabilitation, and could help millions manage their chronic respiratory conditions. Therabron’s market potential is very large; it could be to respiratory disease what insulin is to metabolic disease. The potential for Therabron as a therapy in respiratory indications has recently been reviewed. The source of native CC10 protein is the lungs is airway epithelial cells called Club cells, which are critical to normal airway function, host defense, and post-injury repair and regeneration of airways. Club cell injury is a driver of disease severity in acute lung injuries and obstructive chronic lung diseases. The primary rationale for use of Therabron is as a replacement therapy in respiratory conditions in which the native CC10 protein and Club cells are depleted. CC10 protein supports maintenance of lung homeostasis in part through stimulation of Club cell development and maintenance. It also strongly suppresses inflammatory responses, particularly in the lung, as demonstrated in the lungs of severely premature infants in respiratory distress in which Therabron reduced inflammatory cell counts, inflammatory cytokines, and vascular permeability. Therabron has also demonstrated efficacy by multiple routes of administration in several large animal models of acute respiratory distress syndrome (ARDS) and several murine models of pulmonary fibrosis induced by different types of lung injuries and exposures. References are provided in the supplemental upload.