Biotron (ASX:BIT) has released new data demonstrating significant progress in its Hepatitis B Virus (HBV) development program, with its lead candidate BIT-HBV001 showing potent antiviral effects across multiple laboratory and animal models.
The findings, which include confirmation of activity in two recognised mouse models and firm performance in cell-based assays, position BIT-HBV001 as a promising next-generation therapy targeting viral persistence.
Biotron has been developing a suite of small-molecule antiviral compounds designed to disrupt HBV replication. The company previously reported that several of these compounds were highly active in vitro across a range of cell lines, including primary human hepatocytes. Earlier in 2025, Biotron completed the first stage of mouse studies, confirming BIT-HBV001’s safety and establishing appropriate dosing for further testing.
The newly completed second stage of studies provides the most substantial evidence to date of the drug’s antiviral capabilities in vivo. Conducted at the SCRIPPS Research Institute in California, the work evaluated BIT-HBV001 in two widely used HBV disease models: a genetically engineered mouse that expresses HBV in the liver, and a second model engrafted with human hepatocytes that can be infected with the virus and produce infectious particles.
In both models, mice received regular dosing over 16 days, after which liver and blood samples were analysed. In the engineered Tg05-C57Bl/6 model, BIT-HBV001 reduced HBV DNA levels by approximately 65 per cent, though levels of HBsAg remained unchanged. In the humanised MUP-uPA-SCID/Beige model, the candidate again reduced viral DNA by about 62 per cent, and importantly, also produced a significant reduction in HBsAg of about 48 per cent. Biotron states that this difference reflects the compound’s unique mechanism of action across various stages of HBV replication.
The drug’s performance in laboratory assays appears even more striking. A follow-up in vitro study comparing BIT-HBV001 to tenofovir (TDF), the current first-line therapy for chronic HBV, found that BIT-HBV001 strongly inhibited all five HBV replication markers assessed. These included near-complete inhibition of HBV DNA, HBsAg, HBeAg and pregenomic RNA, as well as a 77 per cent reduction in cccDNA, the persistent viral reservoir that underpins chronic infection.
A further combination study indicated that BIT-HBV001 and TDF act synergistically to suppress HBV DNA, suggesting that lower doses of each drug could achieve the same antiviral effect. While no synergy was observed on other markers, given TDF’s lack of activity, the standard therapy did not interfere with BIT-HBV001’s broader antiviral action.
Biotron Managing Director Michelle Miller said the new results significantly deepen the company’s understanding of the drug’s potential. “These latest animal and cell-based study results significantly advance Biotron’s very promising HBV program,” she said. “We now have a clearer understanding of the mechanism of action of this new class of drug, which has demonstrated advantages over the current standard of care. The inhibition of cccDNA, a marker of HBV persistence, is particularly encouraging.”
Biotron has now filed a patent covering BIT-HBV001 and a series of related small-molecule compounds, including their structures, methods of manufacture and therapeutic use.