December 19, 2025 – Clinical-stage innovative drug R&D company Epigenic (Shanghai) Biotechnology Co., Ltd. (hereinafter "Epigenic") announced today that its innovative epigenetic regulation therapy, EPI-003, has received Investigational New Drug (IND) clearance from the U.S. Food and Drug Administration (FDA) for the treatment of chronic hepatitis B (CHB). EPI-003 is the world's first epigenetics-based therapy utilizing lipid nanoparticle (LNP) delivery technology to receive FDA IND clearance. Currently, Phase I clinical trials for this drug are progressing smoothly in New Zealand, Australia, and Hong Kong. This FDA clearance will significantly advance the global multi-center clinical development of EPI-003.

CHB is a liver disease caused by hepatitis B virus (HBV) infection, which can progress from an asymptomatic stage to cirrhosis, liver failure, or even hepatocellular carcinoma (HCC). The main challenge in curing CHB lies in the persistent presence of HBV covalently closed circular DNA (cccDNA) and HBV DNA integrated into the host genome within liver cells, leading to sustained expression of viral antigens. Current antiviral therapies for hepatitis B can only suppress HBV replication but cannot eradicate these viral "reservoirs," often requiring patients to undergo long-term or even lifelong treatment.

EPI-003 is an intravenous antiviral drug based on a novel mechanism of action. Utilizing an LNP delivery system, the drug precisely delivers mRNA encoding an epigenetic regulatory protein and guide RNA targeting HBV genes to liver cells. This enables durable epigenetic modification of cccDNA and integrated DNA, thereby suppressing the production of all viral products at the transcriptional source. Preclinical studies have shown that EPI-003 can significantly and sustainably reduce levels of hepatitis B surface antigen (HBsAg) and HBV DNA, maintaining long-term efficacy after treatment cessation, demonstrating potential for achieving functional or even complete cure of hepatitis B.

Dr. Zhang Baohong, Co-founder and CEO of Epigenic, stated: "The FDA IND clearance for EPI-003 is a key milestone in its global development pathway. This is not only the first LNP-delivered epigenetic regulation therapy approved by the FDA for clinical trials but also represents substantial progress in leveraging cutting-edge technology to tackle the challenge of chronic hepatitis B. We are committed to advancing clinical studies to bring a transformative treatment option to hundreds of millions of patients worldwide as soon as possible."

This progress marks a milestone not only for the innovative EPI-003 therapy but also signifies a new exploratory phase for epigenetic regulation technology in combating major chronic viral infections.

Enorna is honored to have deeply participated in and supported the CMC development and manufacturing of Epigenic's EPI-003 project through our mRNA and LNP CRDMO platform capabilities. The FDA IND clearance for this project will accelerate its global multi-center clinical development. We look forward to continuing our collaboration to bring this hope for a cure to a broader global patient population.