Secretoglobins (SCGBs) are naturally occurring proteins produced in the body by various organs. The SCGBs produced
in the lungs are some of the most abundant proteins secreted in the airways. Trove and its partners have identified
several SCGB candidates as potential therapeutics, with the lead candidate being recombinant human SCGB1A1
protein, called Therabron™. In healthy individuals, Club cells are abundant in the airway epithelium and they produce
the SCGB1A1 protein, which is the most abundant protein in the fluid that lines the respiratory tract, including the
lungs and nasal airways. SCGB1A1 modulates inflammatory and immune responses to environmental irritants,
pathogens, pollutants, and allergens on airway surfaces, maintains airway epithelial homeostasis, pulmonary immune
homeostasis, and pulmonary vascular homeostasis via several mechanisms of action, and facilitates repair of
damaged airways. The SCGB1A1 protein has been studied extensively and is also known as CC10, CCSP, CC16,
uteroglobin, urine protein 1, UP-1, blastokinin, and PCB-binding protein.
Respiratory tract damage and lung impairment can be caused by numerous insults, including infectious pathogens, allergens, dust or smoke, chemicals, noxious gases, inert particles, and many other potential irritants. When lungs are exposed to these insults, an inflammatory response is triggered, which often causes more physical damage to the lungs, leading to acute lung injury, loss of lung function, and/or long term fibrosis. SCGB1A1 has been shown to be critical in mitigating lung injuries and accelerating airway epithelial repair. In fact, effective lung repair is dependent upon Club cell function and a process called autophagy, which, in turn, requires sufficient SCGB1A1.
SCGB1A1 deficiency: Many patients with acute and chronic respiratory conditions are not able to produce sufficient SCGB1A1 due to a lack of sufficient Club cells and/or their SCGB1A1 genotype. In recurrent and chronic sinusitis, the nasal airway cells that produce SCGB1A1 are replaced by fibrotic cells and scar tissue, resulting in a deficiency of SCGB1A1 which pre-disposes patients towards persistent infections and further scarring, often eventually requiring sinus surgery. There are also well-characterized deficiencies of Club cells and SCGB1A1 in the lungs in several chronic respiratory diseases (CLDs) and conditions, including chronic sinusitis, asthma, COPD, CLAD-BOS, cystic fibrosis, and severe nasal allergy. Similarly, in Acute Lung Injury (ALI), acute respiratory distress syndrome (ARDS), and pneumonia due to influenza-like illness (flu, COVID-19, RSV), smoke inhalation, and other causes, the normal lung epithelial cells are damaged, resulting in loss of Club cells, SCGB1A1 production, and compromised lung function.
Therabron™ is being developed as a therapeutic to treat these respiratory conditions. Therabron™ is a replacement therapy for the missing SCGB1A1 protein and can reduce the severe inflammation, fibrosis, and loss of lung function brought about by disease and injury through its multi-modal effects. The administration of Therabron™ in models of acute and chronic respiratory conditions reduced viral load, reduced pulmonary and systemic inflammation, protected and preserved mechanical lung function and gas exchange, reduced pulmonary edema, reduced pulmonary fibrosis, and stimulated airway repair. Therabron's stimulation of airway repair may facilitate respiratory rehabilitation following hospital discharge, severe infection, and/or inhalation injuries caused by exposures to wildfire smoke, burn pits, occupational exposures, and other airborne inhalation hazards.
Respiratory tract damage and lung impairment can be caused by numerous insults, including infectious pathogens, allergens, dust or smoke, chemicals, noxious gases, inert particles, and many other potential irritants. When lungs are exposed to these insults, an inflammatory response is triggered, which often causes more physical damage to the lungs, leading to acute lung injury, loss of lung function, and/or long term fibrosis. SCGB1A1 has been shown to be critical in mitigating lung injuries and accelerating airway epithelial repair. In fact, effective lung repair is dependent upon Club cell function and a process called autophagy, which, in turn, requires sufficient SCGB1A1.
SCGB1A1 deficiency: Many patients with acute and chronic respiratory conditions are not able to produce sufficient SCGB1A1 due to a lack of sufficient Club cells and/or their SCGB1A1 genotype. In recurrent and chronic sinusitis, the nasal airway cells that produce SCGB1A1 are replaced by fibrotic cells and scar tissue, resulting in a deficiency of SCGB1A1 which pre-disposes patients towards persistent infections and further scarring, often eventually requiring sinus surgery. There are also well-characterized deficiencies of Club cells and SCGB1A1 in the lungs in several chronic respiratory diseases (CLDs) and conditions, including chronic sinusitis, asthma, COPD, CLAD-BOS, cystic fibrosis, and severe nasal allergy. Similarly, in Acute Lung Injury (ALI), acute respiratory distress syndrome (ARDS), and pneumonia due to influenza-like illness (flu, COVID-19, RSV), smoke inhalation, and other causes, the normal lung epithelial cells are damaged, resulting in loss of Club cells, SCGB1A1 production, and compromised lung function.
Therabron™ is being developed as a therapeutic to treat these respiratory conditions. Therabron™ is a replacement therapy for the missing SCGB1A1 protein and can reduce the severe inflammation, fibrosis, and loss of lung function brought about by disease and injury through its multi-modal effects. The administration of Therabron™ in models of acute and chronic respiratory conditions reduced viral load, reduced pulmonary and systemic inflammation, protected and preserved mechanical lung function and gas exchange, reduced pulmonary edema, reduced pulmonary fibrosis, and stimulated airway repair. Therabron's stimulation of airway repair may facilitate respiratory rehabilitation following hospital discharge, severe infection, and/or inhalation injuries caused by exposures to wildfire smoke, burn pits, occupational exposures, and other airborne inhalation hazards.