Shanghai CirCode Biomed Co. Ltd. announced on May 30, 2025, that its lead candidate HM2002 received Investigational New Drug (IND) clearance from the US Food and Drug Administration (FDA) for ischemic heart disease treatment. This milestone establishes HM2002 as the world's first circular RNA drug to achieve regulatory approval for clinical studies in patients with ischemic heart disease.
Regulatory Breakthrough for Circular RNA Technology
HM2002 represents a significant advancement in circular RNA therapeutics, having achieved the distinction of being the first circular RNA therapy to receive IND clearance in both China and the United States. The drug previously obtained IND approval from China's National Medical Products Administration (NMPA) on January 10, 2025, and began treating its first patient in September 2024 through an investigator-initiated trial (IIT).
The regulatory approvals underscore the potential of circular RNA technology to address critical cardiovascular conditions. According to CirCode, ischemic heart disease has been the leading cause of death globally for decades, with steadily rising incidence due to global population aging.
Addressing Unmet Medical Needs
Current standard-of-care treatments for ischemic heart disease demonstrate limited effectiveness in promoting myocardial microcirculation reconstruction and angiogenesis, resulting in suboptimal efficacy and limited benefit in 10-year survival outcomes. This creates an urgent unmet medical need for next-generation therapies that can improve patient prognosis and quality of life.
HM2002 leverages the unique properties of circular RNAs, including improved stability and low immunogenicity, to safely and continuously express vascular endothelial growth factor (VEGF) in the myocardium. This mechanism promotes angiogenesis, improves myocardial perfusion, and facilitates cardiac function recovery.
Clinical Evidence and Safety Profile
The drug has demonstrated excellent safety and efficacy in preclinical studies. In the first-in-human IIT conducted at Ruijin Hospital, all subjects showed significant cardiac function improvement without any drug-related adverse events, providing early validation of the therapeutic approach.
Dr. Chenxiang Tang, CEO of CirCode, explained the therapeutic rationale: "To promote angiogenesis and relief ischemia through VEGF overexpression is a well-tested solution, but there is a tremendous challenge to achieve an efficient, persistent, and controllable expression of VEGF in vivo. We find an excellent match between the need and the properties of circular RNA. A single dose of HM2002 can express VEGF protein for a perfect time window in vivo: long enough for efficient angiogenesis, short enough for any safety concerns."
Platform Technology and Pipeline Development
CirCode's proprietary circular RNA platform enabled rapid development of HM2002, progressing from concept to IND approval in less than two years with the assistance of AI tools. Dr. Yun Yang, co-founder, chairman, and chief technology officer of CirCode, noted that the company has built a robust pipeline portfolio covering therapeutic proteins, vaccines, and in vivo CAR-T applications across multiple therapeutic areas including cardiovascular diseases, infectious diseases, autoimmune diseases, and oncology.
The company reports that many pipeline candidates have demonstrated favorable risk-benefit profiles with strong efficacy and safety data in preclinical settings, with several expected to enter clinical stages within the next year.
Industry Impact
The dual regulatory approvals for HM2002 represent a significant milestone for the circular RNA therapeutic industry. Dr. Tang emphasized that "The IND clearances from both NMPA and FDA for HM2002 is a strong recognition for our innovation and competitiveness in the circular RNA therapeutic industry."
CirCode positions itself as a clinical-stage biotechnology company with a fully integrated and proprietary platform protected by a comprehensive global patent network. The company focuses on unmet medical needs and has received backing from top-tier investors and recognition from leading pharmaceutical companies.
