Biotron (ASX: BIT) has reported a major step forward in its Hepatitis B Virus (HBV) drug development program, confirming robust antiviral activity for its lead compound BIT-HBV001 across two established mouse models and multiple in vitro assays.
The results form part of an extensive series of studies conducted at the SCRIPPS Research Institute in the US to assess the drug’s potential for inhibiting key HBV replication pathways, including those not addressed by current first-line therapies such as Tenofovir.
Biotron also filed a new patent covering BIT-HBV001 and associated compounds, expanding its intellectual property position as the program progresses toward clinical readiness.
In Vivo Activity Across Two Mouse Models
Biotron tested BIT-HBV001 in two complementary mouse models commonly used in HBV research: a transgenic line expressing viral components in the liver, and a human-hepatocyte engrafted model capable of producing infectious virus.
In both models, dosing every 10 hours over 16 days produced significant reductions in HBV DNA, with decreases of about 65% in the transgenic mice and around 62% in the engrafted cohort.
In the engrafted model, BIT-HBV001 also demonstrated activity against an additional marker associated with chronic infection and treatment resistance.
The company said the differing responses between the two models align with the known mechanism of action of its HBV compounds and reflect a broader pattern of antiviral activity across multiple viral markers.
The work builds on earlier studies reported in June that established the drug’s safety profile in mice and identified appropriate dosage ranges for ongoing experiments.
Five Key HBV Replication Endpoints
A further cell-based antiviral study compared BIT-HBV001 directly with Tenofovir using human liver-derived cells infected with HBV and assessed five independent replication endpoints.
BIT-HBV001 produced strong inhibition across all markers, including 99.97% inhibition of HBV DNA, 97% inhibition of HBsAg, 97.6% inhibition of HBeAg, 77.3% inhibition of cccDNA and 99.4% inhibition of pgRNA.
Tenofovir significantly inhibited only HBV DNA, with minimal or no activity on the four remaining endpoints, consistent with its established clinical profile.
The company identified the ability of BIT-HBV001 to inhibit cccDNA — a key driver of viral persistence and a major barrier to achieving functional cure — as a critical differentiator from existing therapies.
These results further validate BIT-HBV001 as part of a new class of HBV drugs capable of targeting pathways beyond those affected by current standard-of-care treatments, and Biotron has now filed a patent covering composition, manufacture, and use of BIT-HBV001 and related molecules.
Synergy With Tenofovir Demonstrated
Biotron also completed a combination study assessing whether BIT-HBV001 and Tenofovir could deliver enhanced activity when used together across a dilution matrix in infected liver-derived cells.
The two drugs showed strong synergy against HBV DNA, indicating lower doses of each compound could achieve equivalent antiviral activity.
No synergy was observed for other endpoints due to Tenofovir’s limited scope of action, but importantly the first-line drug did not antagonise the activity of BIT-HBV001.
“This was an extensive series of experiments with our best HBV drug against a complex challenging virus,” managing director Michelle Miller 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 first-line treatment.”
Chronic HBV infection affects an estimated 250 million people globally and is linked to serious complications including cirrhosis and liver cancer.
