HighTide Therapeutics, Inc. announced that the Phase IIb clinical trial evaluating HTD1801 (berberine ursodeoxycholate), the Company's in-house developed gut-liver anti-inflammatory metabolic modulator, has completed enrollment of patients with metabolic dysfunction-associated steatohepatitis (MASH; also known as nonalcoholic steatohepatitis, NASH) with comorbid type 2 diabetes mellitus (T2DM) or pre-diabetes. This trial (also known as the Centricity study) is a randomized, double-blind, placebo-controlled multi-regional Phase IIb clinical trial evaluating the safety and efficacy of HTD1801 in patients with MASH. Patient enrollment was initiated in December 2022 and a total of 218 patients have been enrolled in the United States, Hong Kong and Mainland China as of the date of this announcement.

The primary endpoint of the Centricity study is improvement in liver histology. The United States Food and Drug Administration had granted HTD1801 Fast Track designation for treating patients with MASH (NASH) in November 2018. MASH is a serious chronic liver disease and a leading cause of liver-related morbidity and mortality - affecting about 5% of the world's population.

Its worldwide prevalence is rising due to the growing obesity epidemic. Without treatment, MASH may progress to advanced fibrosis, liver cirrhosis, hepatic decompensation, hepatocellular carcinoma, and liver transplantation or death. MASH is a clinical manifestation of metabolic syndrome in the liver, closely related to visceral obesity, and is characterized by cardiovascular risk factors such as insulin resistance, T2DM, dyslipidemia, and hypertension.

Patients with MASH and multiple metabolic abnormalities are at greater risk of histological progression and all-cause mortality. Given the disease's pathogenic complexity and heterogeneity, the treatment of MASH is trending toward a multifunctional approach, in particular therapies which target liver fibrosis as well as cardiovascular risk factors (i.e. T2DM, obesity, dyslipidemia). HTD1801, an ionic salt of berberine and ursodeoxycholate, is a new molecular entity with unique mechanisms of action that address the core aspects of MASH through multiple pathways including activation of AMP kinase, and anti-inflammation.

In an earlier Phase IIa MASH trial, HTD1801 met the primary endpoint with a robust reduction in liver fat content following 18 weeks of treatment. HTD1801 also demonstrated important cardiometabolic benefits (e.g., significant reductions in HbA1c, weight, and LDL-C) and non-invasive markers of liver fibrosis and inflammation. The Company is also evaluating HTD1801 as a treatment for T2DM via multiple Phase III trials.