ROCKVILLE, MD and SHENZHEN, CHINA, May 15, 2023— HighTide Therapeutics Inc. (“HighTide”), a globally integrated biopharmaceutical company specializing in the discovery and development of first-in-class multifunctional therapies for metabolic and digestive diseases, today announced that a Phase 2 study in type 2 diabetes (T2DM) achieved its primary endpoint and several important secondary endpoints. In this study, compared to placebo group, treatment with HTD1801 led to a superior reduction in glycosylated hemoglobin (HbA1c) from baseline and was well-tolerated.

This randomized, double-blind, placebo-controlled study enrolled 113 subjects with T2DM with poor glycemic control despite life-style intervention. Approximately 50% of these patients had apparent fatty liver at baseline, consistent with the published epidemiological data. Subjects were randomly assigned to one of two doses of HTD1801 or placebo and treated for 12 weeks.

The results show that HTD1801 resulted in clinically meaningful, statistically significant reductions in HbA1c and fasting glucose compared to the placebo. Further HTD1801 treatment significantly reduced several biomarkers of liver injury and inflammation. HTD1801 was further associated with significant reductions in low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) and was found to be safe and well-tolerated. The results of this trial suggest that HTD1801 has the potential to yield multiple metabolic benefits to patients with T2DM. These findings will be further evaluated in Phase 3 studies in patients with T2DM.

“The target in management of T2DM is not only reducing blood glucose levels but also controlling and improving other related metabolic risk factors, to improve patient outcomes and quality of life. Approximately 55% of patients with T2DM also have non-alcoholic fatty liver disease (NAFLD), and there is a close correlation between the two metabolic diseases. T2DM aggravates NAFLD and results in a higher risk of disease progression and outcomes. Similarly, NAFLD compounds the severity of T2DM and is associated with an increase in comorbidities such as cardiovascular disease and liver-related outcomes.  Therefore, capability in hepatic and cardiovascular protection on the basis of effective glucose reduction is critical when evaluating new, effective therapies for the treatment of T2DM. There remains a significant unmet clinical need for the treatment of patients with T2DM and NAFLD. The clinical results in this Phase 2 study show that HTD1801 significantly improves glycemic control with a good safety and tolerability profile. Additional improvements in lipid metabolism and liver-related parameters were also associated with HTD1801 treatment.  We expect that HTD1801 will offer a better treatment option for patients with T2DM, especially for those also suffering with NAFLD. Further, these results provide us with confidence for the planned Phase 3 trials,” said Professor Linong Ji, Principal Investigator of the study, director of Peking University Diabetes Center, and director of the Department of Endocrinology and Metabolism of Peking University People's Hospital.

Dr. Jiandong Jiang, an academician of the Chinese Academy of Engineering, director of the Institute of Materia Medica of the Chinese Academy of Medical Sciences, and pharmacology expert, also expressed a positive outlook based on the clinical results of HTD1801. “The innovative design of HTD1801 differentiates it from other existing drugs in that it modulates multiple metabolic pathways relevant to T2DM and NAFLD including reduced inflammation and improved intestinal microbiota.”

“In 2004, Dr. Jiandong Jiang’s team published important findings for berberine with Nature Medicine: Berberine Is A Novel Cholesterol-lowering Drug Working through Unique Mechanism Distinct from Statins, which attracted widespread acknowledgment in the scientific community, and gaining traction for the use of berberine for the treatment of metabolic and digestive diseases. Inspired by Dr. Jiang’s work, we designed our unique novel molecule HTD1801 (berberine ursodeoxycholate). Based on the positive findings of our Phase 2 study in T2DM, we plan to initiate a Phase 3 clinical program this year. We believe that HTD1801 will provide a safe and effective comprehensive treatment option for patients with T2DM,” said Dr. Liping Liu, Founder, and CEO of HighTide.

About The Relation between Type 2 Diabetes Mellitus and Nonalcoholic Fatty Liver Disease

HTD1801 is under development for multiple indications, including T2DM and non-alcoholic steatohepatitis (NASH), a more severe form of NAFLD.

Epidemiological data show that 50%-60% of T2DM patients also have NAFLD. The prevalence of NAFLD in T2DM patients was 55.3% in a cross-sectional study of 2420 subjects in six provinces and cities in China. T2DM and NAFLD mutually exacerbate each other; Patients with T2DM and NAFLD have up to a 3-fold greater risk of progression to NASH and a 2-fold greater risk of hepatocellular carcinoma; NAFLD also accelerates the progression of diabetic complications.

For the treatment of T2DM+NAFLD, the "Expert Consensus on the Management of Type 2 Diabetes and Non-alcoholic Fatty Liver Disease" published by the Chinese Society of Endocrinology and Chinese Diabetes Society in 2021, clearly stated the treatment goals of T2DM+NAFLD, i.e., on the basis of controlling the progression of both T2DM and NAFLD, to comprehensively control other risk factors of cardiovascular disease (such as obesity, hypertension, dyslipidemia, hyperuricemia, etc.), as well as to prevent, diagnose, and treat diabetes-related target organ damage and adverse outcome of the liver.

About HighTide

HighTide Therapeutics Inc. is a globally integrated biopharmaceutical company focusing on the discovery and development of first-in-class multifunctional therapies with poly-indications across metabolic and digestive diseases with significant unmet medical needs.  The company is developing multiple clinical assets, including therapy for nonalcoholic steatohepatitis (NASH), type 2 diabetes (T2DM), severe hypertriglyceridemia (SHTG), primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC).  HTD1801, the company’s lead drug candidate, received Fast Track designation from the U.S. for both NASH and PSC, as well as Orphan Drug designation for PSC.  In China, HTD1801 has been included in the National Major New Drug Innovation Program under the 13th Five-Year Plan for Major Technology Project.

For more information, please visit www.hightidetx.com, Contact: pr@hightidetx.com.