Tides Express | Shengen Bio's SGB-7342 (INHBE siRNA) Granted IND Approval in China for Obesity Treatment

Obesity is a chronic metabolic disease caused by a combination of genetic, lifestyle, environmental, and social factors, with the core characteristic being abnormal or excessive fat accumulation that adversely affects health. This condition is a major risk factor for non-communicable diseases such as cardiovascular disease, type 2 diabetes, and certain cancers, and may also influence treatment responses and prognoses for infectious diseases. Currently, the global obese population has exceeded 1 billion, with prevalence continuing to rise in most countries and regions.It is expected to increase to about 1.37 billion by 2035. In China, approximately 180 million adults suffer from obesity.Obesity has become a major global public health challenge.

Currently, therapies represented by GLP-1 receptor agonists primarily achieve weight loss by acting on the central nervous system and suppressing appetite. However, limitations such as gastrointestinal reactions, muscle loss, and weight rebound after discontinuation still need to be addressed. There remains an urgent clinical need for therapies with novel mechanisms of action.RNAi therapy, on the other hand, offers a differentiated treatment strategy.It does not rely on central appetite suppression but instead precisely targets specific genes (such as INHBE) in the fat metabolism pathway, regulating fat metabolism from its source. It aims to achieve selective fat reduction, preserve muscle mass, and comprehensively improve metabolic health while potentially avoiding side effects associated with traditional therapies.

The INHBE gene is primarily expressed in the liver, and its encoded secreted protein, Activin E, regulates lipolysis and storage by binding to the ALK7 receptor in adipose tissue. Genetic studies have shown that individuals carrying INHBE loss-of-function mutations (pLOF) exhibit favorable metabolic health characteristics, such as reduced abdominal fat and lower triglyceride levels.This provides a basis for the development of drugs targeting INHBE: by inhibiting this target, it is expected to mimic this natural advantage, potentially selectively promoting fat breakdown, reducing abdominal and visceral fat, and improving metabolic indicators while avoiding unnecessary muscle loss.Therefore, RNAi therapy targeting INHBE not only holds promise as a new treatment strategy for obesity but also has the potential to be combined with existing standard therapies such as GLP-1, offering patients a more comprehensive solution.Currently, the global development of RNAi therapies for obesity is still in its early stages, but a few drug candidates have entered clinical trials, providing preliminary validation of the significant potential of this therapy in the field of obesity treatment.

AboutSGB-7342

SGB-7342 is an siRNA candidate drug targeting INHBE for the treatment of obesity, developed using SANEGENEBIO's next-generation technology.GalNAcCoupling Technology. Its mechanism of action is to precisely silence the expression of INHBE mRNA in the liver through RNAi technology, reducing the level of its encoded protein Activin E, thereby promoting fat breakdown without inducing muscle breakdown, ultimately improving metabolic abnormalities and insulin resistance. Preclinical trial data show that after a single subcutaneous administration of SGB-7342, potent and long-lasting knockdown of liver INHBE mRNA can be achieved, with significant weight loss, improved body composition, and the expected effect of maintaining muscle observed in animal models, while demonstrating good safety and tolerability.

AboutSANEGENEBIO

SANEGENEBIO is a globally integrated clinical-stage biotechnology company focused on the development of RNAi therapies. Leveraging its proprietary GalNAc liver delivery platform and the industry-leading LEAD™ (Ligand and Enhancer Assisted Delivery) extrahepatic delivery platform, the company is committed to addressing significant unmet clinical needs in the fields of obesity, cardiometabolic diseases, and immune-mediated disorders.