BioCentury
ARTICLE | Distillery Therapeutics

Hepatic

October 17, 2017 4:50 PM UTC

Patient sample and mouse studies suggest inhibiting intestinal HIF2A could help treat hepatic steatosis. In distal ileum biopsies from obese individuals, HIF2A levels and serum levels of hepatic toxicity markers were higher than in non-obese individuals. In mice fed a high-fat diet, intestine-specific knockout of HIF2A decreased weight gain and hepatic lipid drop accumulation and increased insulin sensitivity compared with normal expression. In obese mice with hepatic steatosis, the small molecule HIF2A inhibitor PT2385 decreased body weight, hepatic lipid droplet accumulation, and hepatic and serum levels of cholesterol levels and increased insulin sensitivity compared with vehicle. Next steps include identifying a partner to develop PT2385 for hepatic steatosis or obesity.

Peloton Therapeutics Inc. has PT2385 in Phase II testing to treat advanced clear cell renal cell carcinoma (ccRCC) and von Hippel-Lindau disease-associated ccRCC. ...