A potent and specific first-in-class activator of lyn kinase that promotes insulin sensitization and lipid regulation.
Non-PPAR mechanism of action.
• Type 2 Diabetes
• Nonalcoholic Steatohepatitis (NASH)
- Phase 2 clinical safety & efficacy data in Diabetes
- Over 700 clinical exposures by Q1 2019
- Strong pre-clinical data in NASH
- Potential to initiate NASH U.S. registration studies within 24 months
Overview: Tolimidone is a novel, clinical stage drug candidate for the treatment of Type 2 Diabetes and Nonalcoholic Steatohepatis (NASH). Tolimidone improves glycemic control by selectively activating the enzyme lyn kinase, which has been shown to modulate the insulin-signaling pathway. Tolimidone is the first described specific and direct activator of Lyn kinase that elicits glycemic control activity through potentiation of insulin activity. Tolimidone does not activate the PPAR pathway.
Nonalcoholic Steatohepatitis (NASH)
Nonalcoholic steatohepatitis (NASH), a disease of hepatic fat accumulation, is projected to become the leading cause of liver transplantation by 2020. There are currently no approved therapies for the disease. The market opportunity for future NASH therapeutics is projected to exceed $30 billion.
Lyn kinase is an enzyme that modulates insulin sensitivity and dyslipidemia. Lyn kinase may also play a role in promoting liver regeneration and hepatocyte preservation.
Tolimidone has demonstrated improvement in multiple components of NASH in a comprehensive pre-clinical model of NASH:
- Reduction in NAS score
- Decrease in liver weight
- Reduction in adiposity
- Decrease in insulin resistance
Type 2 Diabetes
This mechanism has now achieved clinical validation by way of a recently completed Phase 2a POC study. Melior’s Phase 2a study enrolled 130 diabetic subjects in a 4-week protocol across 19 sites in the US and Korea, and included mixed meal tolerance tests (MMTT; primary endpoint) on Day 1 and Day 29 as well as weekly fasting plasma glucose (FPG). The study achieved statistically and clinically significant improvements in both MMTT and FPG. Beneficial changes were also observed in all lipid parameters as well as some evidence of weight loss, which was consistent with animal data. The improved lipid profiles and weight loss is consistent with more recent understanding of the mechanism.DOWNLOAD MORE INFO