BrightGene Pharmaceutical Co., Ltd. presented compelling Phase 2 data for its dual GLP-1R/GIPR agonist BGM0504 at the 85th Scientific Conference of the American Diabetes Association, demonstrating superior efficacy to semaglutide in type 2 diabetes treatment and significant weight loss benefits in obesity management.
Superior Diabetes Control Compared to Semaglutide
The multicenter, randomized Phase 2 study in type 2 diabetes enrolled 67 participants aged 18-65 with baseline HbA1c between 7.0% and 10.0% and BMI between 19.5 and 35 kg/m². Participants were randomized into five groups receiving BGM0504 at 5mg (n=13), 10mg (n=12), 15mg (n=13), semaglutide positive control (n=16), or placebo (n=13).
At Week 12 of target dose administration, BGM0504 achieved statistically significant HbA1c reductions across all dose groups compared to placebo, with results exceeding semaglutide performance. The 5mg dose group showed -1.72% reduction, the 10mg group achieved -1.94% reduction, and the 15mg group demonstrated -2.48% reduction, compared to -1.43% for semaglutide and -0.28% for placebo.
Secondary endpoints including postprandial glucose, fasting plasma glucose, body weight, and combined HbA1c/body weight target proportions showed similar superior results for BGM0504. Most treatment-emergent adverse events were Grade 1 or 2 during rapid titration, with common gastrointestinal effects including diarrhea, nausea, and abdominal distension. No hypoglycemic or unexpected adverse reactions occurred.
Significant Weight Loss in Obesity Study
The randomized, double-blind, placebo-controlled obesity study evaluated BGM0504 in 120 Chinese adults with obesity. Participants included adults with BMI ≥24kg/m² (mean BMI ≥27kg/m²) with prediabetes and/or obesity-related comorbidities, or adults with obesity (BMI≥28kg/m², mean BMI ≥30kg/m²). The study design included a 2-6 week titration phase, 24 weeks of once-weekly treatment, and 2-week follow-up.
Results demonstrated substantial waist circumference reductions ranging from -8.0 cm to -12.98 cm (p < 0.001) and significant weight reductions from -10.77% to -19.78% (LS means, placebo adjusted). Blood pressure improvements were also observed, with systolic blood pressure reductions of -11.60 to -13.03 mmHg and diastolic blood pressure reductions of -5.98 to -7.50 mmHg (p < 0.05).
Novel Amylin Analog Shows Enhanced Receptor Activity
Preclinical data for BGM1812, a novel amylin analog designed using AI/ML-driven optimization, revealed superior receptor activation with 1.8× and 2.2× increased agonist activity (EC50) at amylin and calcitonin receptors, respectively, compared to petrelintide. In diet-induced obese rat models, BGM1812 demonstrated dose-dependent weight loss in the 0.012-0.12 mg/kg range.
At 0.04 mg/kg, BGM1812 achieved greater weight reduction than petrelintide while significantly preserving relative lean mass and reducing relative fat mass. The combination of BGM1812 and BGM0504 resulted in greater and more sustained weight loss than either semaglutide plus cagrilintide or amycretin in the DIO rat model.
Clinical Development Progress
BGM0504 is currently in Phase 3 trials in China for weight management and type 2 diabetes and has completed a Phase 1 bridging study for weight management in the United States. To date, BGM0504 has been investigated in more than 1,000 patients, demonstrating superior efficacy and a strong safety profile.
"These Phase 2 data highlight the significant, best-in-class potential of BGM0504 as a treatment for type 2 diabetes and obesity, including potential superiority to semaglutide and a strong safety profile," said Dr. Jiandong Yuan, CEO of BrightGene. "Building on our extensive peptide expertise and strong heritage in high-quality, efficient drug development, BrightGene is committed to accelerating innovative therapeutics to help address unmet patient needs in metabolic disease and other important therapeutic areas."
BGM1812 is designed as a potent and ultra long-acting amylin analog with potential for once-weekly oral tablet administration, representing a significant advancement in obesity treatment convenience and patient compliance.
