SAN DIEGO and KALAMAZOO, Mich., Oct. 20, 2017 /PRNewswire/ -- Cirius Therapeutics announcedtoday that it will present a poster describing the activity of the company's lead drug MSDC-0602K in a diet-induced model of NASH at the American Association for the Study of Liver Diseases (AASLD) – also known as The Liver Meeting – occurring in
The poster, entitled "Acute mitochondrial pyruvate carrier-dependent and -independent effects of MSDC-0602 in hepatocytes on insulin sensitivity and NASH endpoints in mice" will be presented in the Experimental Steatohepatitis session on Monday, October 23 in the Poster Hall from 12:30 to 2:00 PM. The work will be presented by Dr. Kyle McCommis from the Washington University School of Medicine, St. Louis, MO.
This work follows on recently published work demonstrating that attenuation of pyruvate metabolism with MSDC-0602K via modulation of the mitochondrial pyruvate carrier (MPC) can both prevent and reverse liver fibrosis.
The new data presented at AASLD demonstrates that the MPC plays a critical role in stellate cell activation which can drive liver fibrosis. When the MPC was deleted from liver cells or attenuated by MSDC-0602K, stellate cell activation and expression of markers of fibrosis were reduced. There were no further effects on these markers when MSDC-0602K was given to mice who lacked hepatocyte MPC. These data suggest that pyruvate metabolism regulates the release of factors from hepatocytes that contribute to stellate cell activation.
Moreover, the new work shows that there are specific gene expression markers – called miRNAs – in mice that are either increased or decreased in the circulating plasma by the NASH-producing diet, and these effects are precisely reversed by treatment with MSDC-0602K.
"I find these data intriguing because circulating miRNAs can provide a window on to what is going on in the liver and these data suggest that through modifying pyruvate metabolism in hepatocytes, MSDC-0602K can significantly impact the course of liver disease in this mouse model," said Dr. McCommis. "Additionally and importantly, the data show that the pharmacological effect of MSDC-0602K can be detected in the plasma."
Dr. Jerry Colca of Cirius Therapeutics echoed the importance of these results, "These data provide scientific support for our approach with this new type of metabolism modulator. The data also give us a guide on how to develop new tools to facilitate the clinical development of MSDC-0602K."
About MSDC-0602KMSDC-0602K is an oral, once-daily next-generation small molecule that restores metabolic balance at its root — through mitochondrial function — and therefore increases the body's sensitivity to insulin, the hormone that is the master regulator of metabolism. MSDC-0602K, which modulates the entry of pyruvate into the mitochondria, has the potential to correct the metabolic disturbance that is a proximate cause of NASH. Cirius is currently enrolling the EMMINENCE trial, a Phase 2b study of MSDC-0602K in NASH. This randomized study is comparing three doses of MSDC-0602K to placebo in NASH patients with fibrosis, and the study includes endpoints identified as suitable for registration studies based on current FDA guidelines.
About Cirius Therapeutics:Cirius Therapeutics is a clinical-stage pharmaceutical company focused on developing therapies to treat liver disease. The company's lead product is MSDC-0602K, a molecule that restores metabolic balance at its root – through mitochondrial function – and therefore reduces insulin resistance. Cirius is actively enrolling patients in a Phase 2b clinical trial called the EMMINENCE trial, to evaluate MSDC-0602K in patients with NASH and liver fibrosis. For more information about Cirius Therapeutics, visit www.ciriustx.com.
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SOURCE Cirius Therapeutics
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