INI-822 data show favorable drug properties and in vivo changes in lipid metabolism consistent with those observed with protective forms of HSD17B13
Inipharm, a biopharmaceutical company focused on discovering and developing therapies for severe liver diseases, today announced that data on its development candidate INI-822, an inhibitor of HSD17B13, will be presented at the American Association for the Study of Liver Diseases’ (AASLD) The Liver Meeting®, taking place November 4-8, 2022. INI-822 demonstrated anti-fibrotic activity in the human liver cell based “liver-on-a-chip” model of NASH and led to changes in bioactive lipids in Zucker obese rats.
Numerous genetic association studies have confirmed that enzymatically inactive variants of the HSD17B13 protein are associated with a reduced risk of developing more advanced fibrotic disease in alcoholic, non-alcoholic and viral liver diseases. This protective effect may be mediated by effects on bioactive lipids, which have been shown to be substrates for HSD17B13.
INI-822, a small molecule inhibitor of HSD17B13, is Inipharm’s first development candidate and is planned to begin clinical development in 2023. Key findings to be presented at The Liver Meeting include:
- Decreases in fibrotic proteins of up to 45% in alpha smooth muscle actin and 42% in collagen type 1 in cells treated with INI-822 compared to control.
- Lipidomic changes in Zucker obese rats following repeat dosing of INI-822 including a 79-fold increase in the HSD17B13 substrate, 12-HETE, consistent with inhibition of enzymatic activity.
- Potent and selective inhibition of HSD17B13 with attractive safety and PK/ADME profile suitable for oral dosing.
“Bioactive lipids, which are present in liver lipid droplets, are involved in the response to cellular stress and may play a role in the progression to more severe, fibrotic disease,” said Heather Hsu, Ph.D., chief scientific officer of Inipharm. “In addition to improving measures of fibrotic disease in the liver-on-a-chip system, the changes in the bioactive lipid profile observed in animals treated with INI-822 offer evidence of its ability to positively impact liver metabolism.”
Poster details:
Title: INI-822: Targeting HSD17B13, a genetically validated target for chronic liver disease, with a small molecule inhibitor in models of NASH
Date: November 5, 2022
Time: 1:00 pm
About Inipharm
Inipharm is a biopharmaceutical company focused on discovering and developing therapies for severe liver diseases. Inipharm’s lead program is focused on the highly validated genetic target, HSD17B13. Extensive, consistent evidence that genetic variants in expression of HSD17B13 are associated with significantly lower rates and severity of multiple liver diseases. Building on these novel insights into the biologic activity of HSD17B13, Inipharm is advancing a pipeline of small-molecule therapies that target the activity of this protein.
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Contacts
Carolyn Hawley
Evoke Canale
Carolyn.hawley@evokegroup.com
