Pathologic fibrosis underpins the morbidity and mortality of many serious diseases of the liver, lung, kidney, pancreas, eye, heart, skin, skeletal muscle, intestine, and other organs and is estimated to contribute to up to 45% of deaths worldwide.
At its basis, pathologic fibrosis consists of excessive and uncontrolled scar tissue formation. Although driven by varied insults in different diseases, it occurs through shared fibrogenic processes that lead to accumulation of fibroblasts and myofibroblasts and dysregulated deposition of extracellular matrix. Pathologic fibrosis ultimately leads to destruction of normal tissue architecture, organ dysfunction, and, in many cases, organ failure and death.
Non-alcoholic steatohepatitis (NASH) and idiopathic pulmonary fibrosis (IPF), both of which are serious fibrotic diseases with high unmet medical needs, are the indications for Indalo’s initial clinical studies.
NASH is a progressive disease caused by excessive fat accumulation in the liver, unrelated to alcohol use, that induces chronic inflammation and damage (ballooning) of hepatocytes, resulting in fibrosis that can lead to cirrhosis, liver failure, and death.
The stage of liver fibrosis is a strong predictor of clinical outcomes. Ongoing persistence of obesity with increasing rates of diabetes is expected to increase the prevalence of NASH dramatically in coming years, and the disease is projected to become the leading cause of liver transplants in the United States by as early as 2020. There are currently no FDA-approved therapies for NASH, and most therapies currently in development target metabolic or inflammatory processes rather than fibrosis directly.
IPF is an irreversible, relentlessly progressive, and ultimately fatal disease characterized by loss of lung function and impaired gas exchange due to fibrosis.
Patients experience worsening shortness of breath, diminished quality of life, and progressive functional impairment. Median survival time from diagnosis is two to five years, with a five-year survival rate of 20-40 percent. IPF is a large orphan disease, with a prevalence in the United States of approximately 150,000 patients, and with about 35,000 new cases diagnosed each year. IPF remains an urgent unmet medical need despite two approved therapies in the US, each of which has limited market penetration.