Background

Fibrotic interstitial lung diseases are characterized by variable extent of inflammation and fibrosis of lung parenchyma that can affect pulmonary artery remodelling and hypertension, leading to a poor prognosis. GTX-011 is a small molecule in development by GAT Therapeutics for the treatment of fibrotic diseases. It is a TGF? pathway modulator that has proven to reduce fibrosis progression in different models of advanced hepatic fibrotic disease.

Aim

To study the therapeutic potential of GTX-011 in a rat model of pulmonary fibrosis.

Methods

A single intratracheal dose of bleomycin (3.75 U/kg) or sham was administered at day 1 of the 28-day procedure (n=12 per group). GTX-011 2mg/kg, 8mg/kg, or nintedanib 50mg/kg were administered orally, once a day, between day 10 and 28.

Results

100% survival was achieved in the GTX-011 treated groups, compared to 67% in the bleomycin control group and 80% in the nintedanib group. GTX-011 significantly reduced total inflammatory cell count in the bronchoalveolar lavage fluid of treated rats at both doses. Lung tissue hydroxyproline deposition induced by bleomycin was effectively suppressed by GTX 8mg/kg. Both GTX-011 doses fully restored to healthy control values the right ventricular systolic pressure and hypertrophy. GTX-011 at 8mg/kg greatly improved the lung vascular disfunction as assessed in the IVIS system.

Conclusions

GTX-011 treatment significantly improved the survival, lung and heart vascular function, fibrosis and inflammation of our bleomycin model. GTX-011 effects were comparable or better than nintedanib?s. In sum, GTX-011 holds great promise as a therapeutic drug for lung fibrotic diseases.