HighTide Therapeutics presented post-hoc analyses of two Phase 2 clinical studies of berberine ursodeoxycholate (HTD1801) at the 60th European Association for the Study of Diabetes (EASD) Annual Meeting in Madrid, Spain. The studies highlight the potential of HTD1801, a gut-liver anti-inflammatory metabolic modulator, in patients with type 2 diabetes mellitus (T2DM).
Dr. Leigh MacConell, Chief Development Officer of HighTide, stated, "These data provide additional insight on the potential benefits of HTD1801, a novel, multifunctional therapy being developed for the treatment of patients with T2DM." Two ongoing Phase 3 studies (NCT06350890, NCT06415773), fully enrolled in 2Q 2024, are evaluating the efficacy and safety of HTD1801 in T2DM patients as monotherapy or in combination with metformin. Results are expected in 2025.
HTD1801 Efficacy in Diverse T2DM Populations
One presentation focused on comparing the effects of HTD1801 in Chinese and Western patients with T2DM, with or without metabolic dysfunction-associated steatohepatitis (MASH). The analysis revealed that while the two populations are ethnically distinct, treatment with HTD1801 was associated with improvements in key measures of glycemic, cardiometabolic, and hepatic benefit in both groups. This suggests that HTD1801 offers holistic benefits addressing core aspects of both T2DM and MASH, irrespective of underlying disease.
Patients with both T2DM and MASH are at higher risk of histologic progression in MASH, cardiovascular outcomes, hepatic outcomes, and all-cause mortality, making effective treatments crucial.
HTD1801 and Insulin Resistance
The second presentation explored HTD1801's therapeutic approach for patients with metabolic diseases and severe insulin resistance. Insulin resistance is a significant risk factor for T2DM, obesity, and MASH. HTD1801 enhances the utilization of glucose and fats through activation of AMP-activated protein kinase (AMPK), thereby improving insulin sensitivity. The data demonstrated that HTD1801 can alleviate the metabolic inhibitory effects caused by hyperinsulinemia, leading to even greater hepatic and metabolic benefits in patients with more severe insulin resistance, offering a unique therapeutic approach for individuals with T2DM and/or MASH.
HighTide Therapeutics is focusing on developing first-in-class multifunctional multi-targeted therapies for chronic liver and metabolic diseases with significant unmet medical needs. Their lead drug candidate, Berberine ursodeoxycholate (HTD1801), has received Fast Track designation from the U.S. FDA for both NASH and PSC, as well as Orphan Drug designation for PSC.
