CMS (00867) announced that its self-developed innovative small nucleic acid drug, INHBE-targeting CMS-D008 injection, received a drug clinical trial approval notice from China's National Medical Products Administration (NMPA) on March 4, 2026. The NMPA has approved clinical trials of CMS-D008 injection for the treatment of overweight or obesity conditions. CMS-D008 is a subcutaneously administered siRNA drug that targets and inhibits the expression of the inhibin subunit beta E (INHBE) gene in the liver, thereby reducing levels of the INHBE-encoded protein Activin E. This action decreases the activation of the Activin E-ALK7 lipid metabolism pathway, effectively reducing lipid accumulation. Preclinical studies indicate that CMS-D008 efficiently and sustainably suppresses INHBE expression. In obese animal models, the drug demonstrated significant weight loss and fat reduction effects without impacting muscle mass, showing good safety profiles and promising potential for high-quality, long-term weight management that preserves muscle while reducing fat. The drug holds future development potential for treating overweight/obesity, abdominal obesity, and related metabolic diseases. Overweight or obesity is a chronic, progressive, and relapsing disease characterized by excessive accumulation or abnormal distribution of adipose tissue with functional impairments. According to the 2025 World Obesity Report, the global proportion of overweight and obese adults is projected to reach 50% by 2030, affecting nearly 3 billion adults with high body mass index (BMI). In China, the number of overweight/obese adults is expected to reach 515 million. Existing GLP-1 receptor agonist drugs have demonstrated significant weight loss effects primarily by suppressing appetite through central nervous system action and delaying gastric emptying. In contrast, INHBE's mechanism of action differs from GLP-1 class drugs, having been identified through genome-wide association studies. Populations with INHBE loss-of-function exhibit favorable body fat distribution and beneficial metabolic characteristics. Targeted inhibition of INHBE can precisely reduce visceral fat at the genetic level and improve metabolic status, offering advantages for long-term weight management. CMS-D008 will create synergistic effects with the company's self-developed innovative drug CMS-D005, which is currently in clinical development. While CMS-D008 precisely inhibits INHBE gene expression to reduce fat without muscle loss, CMS-D005 acts as a GLP-1R/GCGR dual agonist that can effectively reduce liver fat during weight loss. The combination of these two drugs is expected to achieve efficient weight loss benefits and long-term outcome maintenance, collectively enhancing the group's R&D capabilities and product competitiveness in the obesity/metabolic treatment field. Leveraging the group's established network resources in cardiovascular metabolic diseases, this will accelerate drug development and commercialization processes, providing patients with more comprehensive and innovative treatment options. The group is actively preparing to conduct relevant clinical trials with the goal of bringing this product to market as soon as possible.
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