Xiyan Biologics Receives CDE Acceptance for IND Application of LDR2515, an siRNA Therapeutic for Obesity

According to a 2023 statistic, the global prevalence of obesity is projected to increase from 14% in 2020 to 25% by 2035, affecting approximately 1.9 billion people, indicating that obesity has become a global public health concern. Current treatments for obesity mainly include lifestyle interventions, pharmacotherapy (such as GLP-1 receptor agonists), and surgical procedures. However, studies show that less than 1% of obese patients currently receive pharmacotherapy, while the global market for obesity drugs is experiencing significant growth. Existing medications, such as the new generation of weight-loss drugs like GLP-1 receptor agonists, still face challenges such as gastrointestinal side effects (e.g., nausea, vomiting, diarrhea), muscle loss, and weight rebound after discontinuation. Therefore, the demand for drugs that can provide long-term, stable, and high-quality treatment for obesity is increasing.

The INHBE gene is primarily expressed in the liver, and its encoded protein, Activin E, promotes lipid accumulation. Human genomic studies have shown that loss-of-function mutations in the INHBE gene improve waist-to-hip ratio, reduce abdominal fat, enhance metabolic status, and lower the risk of cardiovascular disease and type 2 diabetes. Consistent with human genomic research, INHBE siRNA in obese mouse models induces sustained weight loss without affecting food intake. Moreover, when combined with a GLP-1 receptor agonist, it enhances weight loss, mitigates muscle loss caused by the GLP-1 receptor agonist, and suppresses weight rebound after discontinuation of the GLP-1 receptor agonist. Preclinical studies indicate that LDR2515 is safe, effectively and continuously inhibits INHBE expression in the liver through subcutaneous injection, and is expected to achieve dosing intervals of once every six months to one year in clinical settings, offering a new therapeutic option for high-quality weight loss and metabolic health!