Epigenic Therapeutics has announced that it has received clearance from the New Zealand Medicines and Medical Devices Safety Authority (Medsafe) and The Health and Disability Ethics Committees (HDEC) to commence a clinical trial for EPI-003, a first-in-class epigenetic inactivator for the treatment of chronic hepatitis B (CHB). This marks a significant milestone as EPI-003 is poised to become the first epigenetic therapy to enter clinical trials for this widespread infectious disease.
First-in-Human Study Design
The upcoming first-in-human study is designed to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of EPI-003 in patients with chronic hepatitis B who are currently undergoing treatment with Nucleos(t)ide Analogues. The clinical trial is planned to be conducted across sites in New Zealand, Australia, and Hong Kong.
EPI-003: A Novel Approach to HBV Treatment
EPI-003 is an investigational antiviral drug administered via intravenous infusion, specifically targeting the liver through epigenetic modification to combat chronic HBV infection. Chronic hepatitis B, if left untreated, can advance from asymptomatic stages to severe conditions such as cirrhosis, liver failure, and hepatocellular carcinoma (HCC). A key challenge in curing CHB lies in the persistent presence of HBV covalently closed circular DNA (cccDNA) and integrated genomic DNA within the liver, leading to sustained viral surface antigenemia. Current antiviral treatments primarily suppress HBV replication, necessitating lifelong medication for patients.
Mechanism of Action
EPI-003 leverages advancements in epigenetic regulatory mechanisms, which have emerged as promising therapeutic targets for HBV treatment. The drug, formulated as mRNA encoding an epigenetic modulation protein and a guide RNA targeting an HBV-specific gene, is encapsulated in a lipid nanoparticle (LNP) delivery system. This design facilitates specific epigenetic modifications on the HBV genome. Preclinical studies suggest that EPI-003 can directly inhibit the transcription of HBV cccDNA and integrated DNA, leading to a substantial and sustained reduction in HBV surface antigen (HBsAg) and HBV DNA levels without viral rebound. This positions EPI-003 as a potential functional or even complete cure for individuals with chronic HBV infection.
Executive Perspective
Bob Zhang, CEO and Co-founder of Epigenic Therapeutics, stated, "We are very pleased to receive the global first CTA approval of EPI-003, a liver-targeted anti-HBV epigenetic inactivator discovered by Epigenic’s proprietary epigenetic regulation technology (EPIREG®), to initiate first-in-patient evaluation of EPI-003...We will work closely with clinical investigators to accelerate clinical development on EPI-003 in order to benefit the CHB patients as soon as possible."
