June 26, 2023, China, Shanghai

Hua Medicine (the "Company", HKEx stock code: 2552) today announces that multiple basic and clinical findings of HuaTangNing (华堂宁®, dorzagliatin), the Company’s global first-in-class glucokinase activator (GKA), were presented at the 83rd American Diabetes Association (ADA) Annual Scientific Sessions. A basic research showed that low-dose dorzagliatin has the potential in decelerating glycemic elevation and preventing cognitive dysfunction in diabetes rat model. Several other studies further proved that dorzagliatin restores islet functions in Type 2 diabetes (T2D) human islets and in diabetes mouse models, providing more mechanistic explanations on diabetes remission of dorzagliatin observed in clinical studies.

Dorzagliatin has the potential to prevent cognitive impairment

The Goto-Kakizaki (GK) rat is a non-obese animal model of type 2 diabetes. With age, GK rats gradually and spontaneously exhibit diabetes-related phenotypes such as insulin resistance, decreased pancreatic islet function, and hyperglycemia, and many studies have also shown that GK rats experience cognitive and memory-related degeneration. The purpose of this study is to elucidate the potential link and correlation between hyperglycemia and cognitive impairment, and to investigate how prolonged administration of low dose dorzagliatin protects GK rats against hyperglycemia and cognitive dysfunction.

The study showed that compared to the vehicle control group, low-dose administration of dorzagliatin for 26 weeks significantly curbed the elevation of fasting blood glucose (FBG) in GK rats, while the memory function was effectively protected. Prolonged administration of low dose dorzagliatin prevented the decline of protein expression of insulin receptors in hippocampus of GK rats, and stabilized the protein expression of glucose transporters in the same area.

The above studies suggest that dorzagliatin protects glucose metabolism of GK rats as it curbs the decline of glucose metabolism in GK rat’s brain, thus playing a role in protecting memory function. In another word, dorzagliatin can effectively curb the disease progression of hyperglycemia and cognitive impairment in spontaneously diabetic rats with age. It also has the potential of preventing cognitive impairment. This study suggests a new potential therapeutic area for dorzagliatin.

Dorzagliatin can restore the function of pancreatic islets that may explain why dorzagliatin induces the remission of diabetes

Hua Medicine also announced a translational study jointly held by Hua Medicine, Nanjing AscendRare Pharmaceutical Technology (a wholly owned subsidiary company of Hua Medicine), and the University of Pennsylvania, which compared the impact of dorzagliatin on enzyme of glucokinase (GK) and islet function (including type 2 diabetic human islets and mouse islets) to the other GKAs.

Both human islet and animal model studies have shown that, different from previous GKAs, dorzagliatin is a glucose concentration-dependent GKA. Therefore, it restores the Vmax of GK while improving the function of GK as a glucose sensor. The improved GK functions and expressions facilitate the recovery of islet functions, and ultimately restore glucose homeostasis. This is a key factor that advanced dorzagliatin ahead of other GKAs in clinical studies and commercial launching. It is also provided the direct evidences of dorzagliatin in restoring the islet function of T2DM patients.

Another mechanism study also proved that dorzagliatin can restore the function of pancreatic islets even after drug withdrawal in diabetes mouse model, that may  provide the explanation of the mechanism of dorzagliatin-induced the remission of diabetes. In this study, dorzagliatin was administrated for short period of time in high-fat diet-induced obese and diabetic mice model, then the islet function was evalsuated after drug withdrawal. The study has shown that dorzagliatin can restore β-cell function in diabetic and obese mice for long period of time after drug withdrawal. Dorzagliatin also significantly improved glycogen metabolism and insulin resistance in the liver of obese mice. The study provides a mechanistic explanation for dorzagliatin-induced diabetes remission.

The effect of dorzagliatin on hepatic glycogen metabolism may be one of the mechanisms for restoring glucose homeostasis in the liver and improving hepatic insulin sensitivity. As dorzagliatin improves islet glucose sensitivity and hepatic insulin sensitivity, it also increases the gene expression of GK, which may be the main reason for diabetic remission observed clinically.

In addition to those studies, Peking University Third Hospital announced a quantitative pharmacology study jointly conducted with Hua Medicine, which revealed the impact of dorzagliatin on β cell protection in patients with T2DM via oral minimal model.

Hua Medicine and AscendRare also presented more results through poster presentations, including studies of gain-of-function mutation of glutamate dehydrogenase, and the early phase development of new drugs for treatment of rare diseases of congenital hyperinsulinism.

About Hua Medicine
Hua Medicine is an innovative drug development and commercialization company based in Shanghai, China, focused on developing novel therapies for patients worldwide with unmet medical needs. Based on global resources, Hua Medicine teams up with global high-caliber people to develop breakthrough technologies and products, which contribute a global innovation in diabetes care. As Hua Medicine's cornerstone product (dorzagliatin tablets), targeting the glucose sensor, glucokinase, restores glucose sensitivity in T2D patients and stabilizes the imbalance of blood glucose levels in patients, it has been approved by the National Medical Products Administration (NMPA) of China on September 30th, 2022. It can be used alone or in combination with metformin hydrochloride-tolerated T2D patients. For those patients with chronic kidney disease (CKD) and Type 2 diabetes (i.e., diabetes kidney disease), no dose adjustment is required. Hua Medicine will partner with Bayer, a leading global pharmaceutical company, to commercialize HuaTangNing (华堂宁®) in China, benefiting diabetic patients and their families. HuaTangNing (华堂宁®) has also demonstrated its potential of achieving diabetes remission in clinical studies to help millions of diabetic patients around the world.

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