Beijing, China, March 08, 2024 — Gan & Lee Pharmaceuticals (hereinafter referred to as "Gan & Lee", stock code: 603087.SH) announces today that the first subject has been dosed successfully in a Phase I clinical trial in China for its independently developed innovative oral peptide-class GLP-1 receptor agonist (GLP-1 RA) — GZR18 tablet, aimed at treating Type 2 Diabetes Mellitus (T2DM).

The single-center, randomized, open-label Phase I clinical study conducted by Gan & Lee Pharmaceuticals aims to evaluate the relative bioavailability, pharmacokinetics, pharmacodynamics, safety, tolerability, and the impact of meal timing on the pharmacokinetics, pharmacodynamics, safety, and tolerability of the GZR18 tablet in healthy adult subjects in China. The trial plans to enroll 116 healthy adult participants.

Diabetes, a metabolic disease characterized by abnormal glucose metabolism, is primarily due to impaired insulin production or response, leading to ineffective blood glucose maintenance. T2DM, the most common form, constitutes the vast majority of diabetes cases worldwide, with its onset linked to complex causes including genetic factors and poor lifestyle habits, such as lack of exercise and obesity.¹ Glucagon-like peptide-1 (GLP-1) is a crucial hormone secreted by intestinal L cells, regulating insulin and glucagon secretion based on blood glucose levels to maintain glucose stability. GLP-1 RAs, developed in recent years, mimic the function of GLP-1 to activate GLP-1 receptors, controlling blood glucose levels. Beyond glucose regulation, GLP-1 RAs have shown clinical benefits, such as aiding weight control and improving non-alcoholic fatty liver disease, gradually becoming the preferred medication for diabetes treatment over traditional insulin therapies. Despite most GLP-1 RAs being injectable, oral GLP-1 RAs, favored for convenience and better patient experience, represent a new research direction in diabetes treatment.²

In the development of oral GLP-1 RAs, challenges for peptide-class drugs include overcoming gastrointestinal structural and functional barriers, like proteolytic degradation and the gastrointestinal wall barrier. Scientists enhance absorption and bioavailability in the gastrointestinal tract by integrating absorption enhancers into peptide medications. GZR18 tablet employs an advanced oral delivery technique, enhancing drug absorption in the stomach and extending the drug's half-life by resisting gastric protease degradation, thereby improving the bioavailability of GZR18. Prior clinical studies of GZR18 injection for T2DM and obesity/overweight management in China and the USA have preliminarily validated its excellent safety and efficacy. This Phase I clinical trial of the GZR18 tablet in China marks the first-in-human clinical study of GZR18's oral formulation, aiming to expedite the development of GZR18 and potentially offer patients more convenient treatment options domestically.

About GZR18

GZR18, developed by Gan & Lee, is a GLP-1 receptor agonist intended for the treatment of T2DM in adults and for weight management in obese/overweight individuals. Preclinical data suggests that GZR18 has potential benefits in reducing blood glucose levels and weight. Some clinical studies have confirmed its efficacy in these areas, and it has a good safety profile. Currently, the global development of GZR18 has entered the Phase II clinical research stage.

References：

1.     Chin J Diabetes Mellitus, 2021, 13(4): 315-409. DOI: 10.3760/cma.j.cn115791-20210221-00095.

2.     Zheng Li, et al., Research Progress of Oral Glucagon-Like Peptide-1 Receptor Agonists and Consideration of Non-clinical Evaluation. Chinese Pharmaceutical Affaris, 2023,(7):825-833. DOI：10.16153/j.1002-7777.2023.07.012

About Gan & Lee

Gan & Lee Pharmaceuticals has developed the first Chinese domestic biosynthetic human insulin. Currently, we have six core insulin products, including five insulin analog varieties: long-acting glargine injection (Basalin^®), fast-acting lispro injection (Prandilin^™), fast-acting aspart injection (Rapilin^®), mixed protamine zinc lispro injection (25R) (Prandilin^™25), aspart 30 injection (Rapilin^®30), and one human insulin injection - mixed protamine human insulin injection (30R) (Similin^®30). We have two approved medical devices in China, namely reusable insulin injection pen (GanleePen), and disposable pen needle (GanleeFine^®).

In the future, Gan & Lee strives to achieve a comprehensive coverage in the field of diabetes diagnosis and treatment. Moving forward to advance our goal of becoming a world-class pharmaceutical company, we will also take an active part in developing new chemical entities, and work on the treatment of cardiovascular diseases, metabolic diseases, cancer, and other therapeutics.