PERTH, Australia – Biotron Ltd. is crunching the data from a recently concluded phase II trial in HIV-1 that tested its lead compound BIT-225 in combination with antiretroviral (ARV) drugs, and the Melbourne-based company said it believes its approach to tackling viruses like HIV could wipe out the virus completely, Biotron CEO Michelle Miller told BioWorld.

Its premise is that BIT-225 is different from other HIV drugs in that it specifically inhibits HIV replication in monocyte/macrophage reservoirs. Monocytes get infected the same way that T cells do, but they differentiate into macrophages where they slowly replicate the HIV virus at low levels where they infect T cells.

Although current ARV drugs wipe out that part of the infection, "it's like a burning ember that is slowly ticking away in the body," Miller said, "and when you take patients off drugs, the virus returns."

Biotron's focus is on designing new drugs that target viroporins, a new class of viral protein found in a broad range of viruses. BIT-255 targets the vpu protein of HIV-1, which is critical for macrophages, but not necessarily for T cells, Miller said, noting that existing HIV drugs do have some effect on macrophages, but they aren't very effective.

She explained that most of the work in reservoirs has been focused on latently infected T cells to flush the virus out with ARVs.

Biotron's approach is complementary to ARV therapy, and the company is betting on the drug to eradicate the HIV virus. The recent combination study was designed to demonstrate that BIT-225 provides an antiviral benefit over and above that of ARV by targeting HIV-1 in macrophage reservoirs.

The phase II multicenter randomized, placebo-controlled study compared BIT-225 with combination ARV drug Atripla (efavirenz/emtricitabine/tenofovir) in treatment-naive patients infected with HIV-1. Preliminary data indicate there were no major interactions between BIT-225 and the other HIV-1 drugs.

The company is using a new diagnostic assay to demonstrate that BIT-225 can specifically target reservoir cells that remain infected in the presence of current ARV drugs. The assay is extending the analyses, but it will form an important part of the company's overall cure strategy for HIV-1.

"Current HIV drugs are very good, but there's still problems with having the virus in your body long term. The immune system ages more quickly and there are other problems such as HIV-associated neurocognitive disorder, or AIDS-related dementia," Miller said.

The drug could help ameliorate some of those symptoms because monocytes producing HIV cross the blood-brain barrier and differentiate into microglial cells, and BIT-225 is able to cross the blood-brain barrier.

Reducing viral burden in macrophage reservoirs

A previous phase II monotherapy trial in treatment-naïve patients showed that BIT-225 could target HIV and reduce viral burden in those macrophage reservoir areas, Miller said. The drug has shown substantial safety and tolerability in phase I and phase II trials.

"The trial confirmed what we saw in cell cultures, and the recently concluded phase II combination trial should confirm those findings," she said. "We're looking to see additional benefit beyond ARV drugs."

A recently published scientific paper validates Biotron's approach of eliminating HIV-1 in macrophages. Published in Nature Medicine in April, the study reported that humanized mice infected with HIV-1 established a persistent infection of virus in tissue macrophages despite treatment with antiretroviral therapy. The study authors concluded that tissue macrophages are critical contributors to HIV-1 pathogenesis and a major barrier to eradicating HIV-1.

"The results from this study uphold Biotron's approach to treatment of HIV-1 infection. BIT-225 specifically targets HIV-1 in macrophages. This recently reported study clearly demonstrates the need for new drugs to eradicate the virus in this persistent reservoir," Miller said.

BIT-225 has completed seven clinical trials in HIV-1 and hepatitis C virus (HCV). Miller said the company wanted to combine HCV and HIV, and she sees particular opportunities in China, where the company is also pursuing programs in hepatitis B virus (HBV).

BIT-225 targets the HCV p7 protein, and in vitro studies have shown pan-genotypic activity in HCV infectious clone assays.

The company also has a pipeline of preclinical antiviral programs in dengue, Zika and influenza virus.

Biotron raised A$1.47 million (US$1.08 million) in June to expand its HBV program.

Miller said Australian companies are very good at making money go a long way, and Biotron will only raise money as it needs it. Before she came to Biotron in 2002, Miller worked as a venture capitalist, which has helped her to know when the next key valuating milestone was coming up before going to the capital market.

Before her VC stint, Miller was at Johnson & Johnson developing HIV gene therapies. She worked in the first gene therapy trials in the early 1990s.

Biotron raised $12 million in its IPO on the Australian Securities Exchange (ASX:BIT) in 2001. It has a market cap of A$11 million.