• In Phase Ia clinical study, GZR4 demonstrated favorable safety and tolerability profiles in healthy subjects, maintaining a stable glucose-lowering effect for up to one week with a single administration.

• In Phase Ib clinical study, patients with Type 2 diabetes mellitus (T2DM) receiving six weeks of GZR4 treatment were safe and well tolerated. GZR4 also exhibited improvements in fasting blood glucose (FBG), glycated hemoglobin (HbA1c), and time in range (TIR) across all dosage groups, outperforming the insulin degludec (IDeg) group.

Beijing, China, 14 September 2024 -Gan & Lee Pharmaceuticals (Gan & Lee, Shanghai Stock Exchange: 603087) announced the clinical results from two Phase I trials of the Company's independently developed novel once-weekly insulin analog, GZR4, in healthy Chinese subjects and patients with T2DM in oral presentation and short oral discussion at the 60th Annual Meeting of the European Association for the Study of Diabetes (EASD 2024).

Statement:

1. GZR18 injection is an investigational drug and has not yet been approved in China.

Gan & Lee Pharmaceuticals does not recommend the use of any unapproved drugs/indications.

Phase Ia Study Results

This placebo-controlled and active-comparator-controlled, single-center, single-dose,  randomized, dose-escalation study aimed to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of GZR4 in healthy adult male participants. The study was conducted following a dose-escalation design, starting from lower doses and progressively increasing to higher doses. Participants in cohorts 1-4 randomly receiving a subcutaneous injection of GZR4 (1, 3, 6, or 12 nmol/kg) or placebo, while cohort 5 received a single dose of 0.4 U/kg (2.4 nmol/kg) insulin degludec (IDeg) as an active comparator. A 24-hour glucose clamp procedure was conducted on days 2 and 7 respectively post-GZR4 administration in cohorts 2-4, and on day 1 post-IDeg administration in cohort 5.

GZR4 exhibited favorable safety and tolerability in healthy subjects, with no serious adverse events (SAEs) reported, and no discontinuations due to the investigational product-related adverse events. PD results indicated that the glucose infusion rate (GIR) on day 7 was approximately 80% of that on day 2 in subjects receiving 12 nmol/kg GZR4, indicating that the glucose-lowering effect of GZR4 persists for approximately one week. Meanwhile, the area under the GIR-time curve on day 2 (AU_CGIR,24-48h) and day 7 (AUC_GIR,144-168h) for the 6 nmol/kg dose of GZR4 was similar to the 24-hour GIR (AUC_GIR,0-24h) for the 0.4 U/kg (2.4 nmol/kg) of IDeg (37.84 ± 9.86 versus 40.60 ± 14.39 h*mg/kg/min, respectively)^*, implying that the average daily glucose-lowering effect of GZR4 is comparable to that of IDeg. Convert accordingly, it is estimated that the potency of GZR4 is approximately 2.5-fold greater than that of IDeg when evaluating based on a similar molar concentration.

Phase Ib Study Results

In this randomized, open-label, active-controlled, multi-center, dose-escalation Phase Ib trial, a total of 36 patients with T2DM who had previously been treated with basal insulin were randomized in a 3:1 ratio to receive a fixed once-weekly dose of GZR4 (6, 8, or 12 nmol/kg) or once-daily (IDeg) (equal to the pre-enrolment daily basal insulin dosage) for 6 weeks.

PK results showed that the maximum plasma concentration (Cmax) of GZR4 increased dose-dependently, while the time to maximum concentration (Tmax) and half-life were approximately 32 hours and 135 hours at steady state, respectively. PD data indicated dose-dependent reductions in FBG (-1.77 ± 0.20, -2.03 ± 0.66, and -2.75 ± 0.71 mmol/L for GZR4 in 6, 8, and 12 nmol/kg groups, respectively) in week 6, which outperformed the IDeg group (-1.12 ± 0.36 mmol/L^*). After 6 weeks of treatment, the 6 nmol/kg GZR4 group demonstrated a reduction in HbA1c of 0.76 ± 0.14%, compared to the reduction of 0.13 ± 0.21% ^* in the IDeg group. 

In patients with T2DM, GZR4 demonstrated good safety and tolerability. No serious adverse events were reported in all treatment groups; the most frequently reported treatment-emergent adverse event was hypoglycaemia, but no severe hypoglycemia occurred.

The detailed results of the Phase I studies will be published in a peer-reviewed journal.

*Trial data are presented as mean ± standard error.

Gan & Lee Pharmaceuticals also announced announced that a multicenter, randomized, open-label, parallel-control, treat-to-target phase 2 study is underway in patients with T2DM who have inadequate glycemic control with oral antidiabetic drugs, including insulin-na?ve patients and patients on basal insulin. The study enrolled 179 adult participants and compares the efficacy and safety of once-weekly GZR4 with once-daily insulin degludec. All participants have completed treatment, and preliminary results are promising, further validating the findings from the Phase I studies.

Dr. Gan Zhong-ru, Chairman of Gan & Lee Pharmaceuticals, commented: “A significant number of patients with Type 2 diabetes mellitus are experiencing delays in initiating insulin therapy and exhibit poor long-term adherence to treatment,etc. The introduction of weekly insulin preparations has the potential to significantly improve the aforementioned challenges. The completed Phase I trials confirmed GZR4’s ability to provide stable glycemic control for a full week with a single dose, along with favorable safety and tolerability profiles. In addition, GZR4 is expected to reduce the weekly dosage of insulin required reaching the glycemic target, thereby reducing the possible risk of hypoglycaemia.We look forward to continuing to explore the clinical benefits of GZR4 in future trials.”

Forward-looking statements

Forward-looking statements are based on our expectations and assumptions as of the date of the statements. Actual results may differ materially from those expressed in these forward-looking statements due to a variety of factors, and we can give no assurance that such results will be achieved in the future. We undertake no obligation to update or revise any forward-looking statements, whether as a result of new information, future events, or otherwise.

About Gan & Lee

Gan & Lee Pharmaceuticals developed the first Chinese domestic insulin analog. Currently, Gan & Lee has 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). The company has two approved medical devices in China, namely reusable insulin injection pen (GanleePen), and disposable pen needle (GanleeFine^?).

In China's 2024 National Insulin-Specific Centralized Procurement, Gan & Lee Pharmaceuticals ranked second overall and first among domestic companies in terms of procurement demand for insulin analogs. The company is also making strides in international markets, with the disposable pen needle (GanleeFine^?) approved by the US Food and Drug Administration (FDA) in 2020 and received GMP inspection approval from the European Medicines Agency (EMA) in 2024. These achievements significantly boost Gan & Lee’s competitiveness in both international and domestic markets.

In the future, Gan & Lee will strive for comprehensive coverage in diabetes treatment. Moving forward with its mission to become a world-class pharmaceutical company, Gan & Lee will also actively develop new chemical entities and biological drugs, focusing on treatments for metabolic diseases, cardiovascular diseases, and other therapeutic areas.