Fibrosis, or scarring, is defined by the accumulation of excess fibrous connective tissue in an organ or tissue undergoing a reparative or reactive process. Left unchecked, the fibrotic process can lead to end-organ failure and eventual death. Fibrosis can occur in nearly every tissue of the body and is a prominent pathological feature of many chronic inflammatory diseases.
STAT3 plays an essential role in fibrogenesis across many diseases. Strikingly, loss of only one STAT3 gene protects mice from bleomycin-induced lung fibrosis (a model of idiopathic pulmonary fibrosis, Kasembeli et al, International Journal of Molecular Sciences, 2018) and skin fibrosis (a model of scleroderma, Pedroza et al, Rheumatology, 2017). Notably, genetic deletion of STAT3 in mice also blocks the development of liver cirrhosis which is the seventh leading cause of death by disease worldwide.
Given the significant numbers of patients affected and the lack of therapies for these fibrotic diseases, Tvardi is focused on the development of safe and effective STAT3 inibitors for use across these fibrotic diseases.
Idiopathic pulmonary fibrosis
Idiopathic pulmonary fibrosis (IPF) is a lung disease characterized by progressive fibrosis of the interstitial lung space. IPF affects ~130,000 individuals in the United States alone. The current standard of care only slows progression; oxygenation becomes significantly impaired requiring continuous oxygen and ultimately lung transplantation.
TTI-101 treatment reversed hypoxia (left panel) and pulmonary fibrosis (right panel) induced by bleomycin. Pedroza M et al, FASEB J, 2015