• BIT225 administered orally significantly reduced viral load in the lungs and blood of animals challenged with SARS-CoV-2.
• BIT225 protected against severe disease, indicated by the significant prevention of body weight loss in animals treated with BIT225 compared to non-treated controls.
• Pro-inflammatory cytokines were also significantly reduced in the lungs and blood of BIT225 treated animals compared with controls. Raised pro-inflammatory cytokines are associated with severe illness in people with COVID-19. Eliminating the "cytokine storm" is essential for successful treatment.
• The results show statistically and clinically significant efficacy of BIT225 in this model of COVID-19.
• In a cell culture in vitro study BIT225 was active against the highly infectious delta variant of SARS-CoV-2, reducing the level of virus by more than 99.99% compared to controls.
• BIT225 is a clinical stage drug in development for treatment of HIV-1, with over 200 people dosed in trials to date. It is an oral drug, suitable for once-a-day dosing and has a well characterised safety profile. Biotron Limited is now seeking to accelerate BIT225 into clinical trials in SARS-CoV-2-infected patients.

SYDNEY, Nov. 25, 2021 /PRNewswire/ -- The Directors of Biotron Limited (ASX: BIT) are pleased to announce that the Company's lead clinical asset, BIT225, has demonstrated substantial and clinically meaningful efficacy against SARS-CoV-2 in a series of animal and cell-based studies performed at The SCRIPPS Research Institute, La Jolla, CA, USA.

BIT225 was tested in a COVID-19 mouse model (K18-hACE2). These mice have been engineered to be infectable by SARS-CoV-2 which then produces a range of pathologies including pulmonary disease. This model is routinely used to assess the ability of drugs to target SARS-CoV-2 and treat COVID-19 disease.

The study in the COVID mice showed that BIT225 given orally (by mouth) significantly reduced virus load in the lungs of treated mice when compared with control mice that were given drug-free control material (known as vehicle control). There was also a reduction in virus in the blood. The reduction in virus was dose-dependent - i.e. reduction in viral load was greater at the higher dose.

Increased levels of pro-inflammatory cytokines ('cytokine storm') are linked to severe illness and death in people infected with SARS-CoV-2 virus. Controlling this cytokine storm is essential for successful treatment of COVID-19.

BIT225 significantly reduced all assayed pro-inflammatory cytokines and chemokines, including IL-6, IL-1α, IL-1β, TNF-α, TGF-β and MCP-1, in the lungs and blood of BIT225- treated mice compared to control mice.

During the course of infection with SARS-CoV-2, K18 mice generally develop severe disease that is reflected in the loss of body weight. The animals treated with BIT225 did not lose weight throughout the study and, in fact, significantly increased their weight in line with growth expectations of the age of the animals.

The impact of BIT225 on the proinflammatory cytokines and on overall health, indicated by preventing loss of body weight, indicates clinically significant benefit of BIT225.

In addition to the in vivo animal study, BIT225 was tested in an in vitro study in cell cultures to assess the ability of the drug to inhibit the highly infectious delta strain. The data showed that BIT225 reduced the delta virus in the cell cultures by more than 99.99% (over 4 logs reduction).

The in vivo study demonstrates that BIT225 is highly effective antiviral agent and protects the animals from severe disease. The in vitro study demonstrates that BIT225 is also active against the highly infectious delta strain of SARS-CoV-2.

BIT225 belongs to a new class of antiviral drugs known as viroporin inhibitors. It targets key viral-encoded proteins known as viroporins that are central to establishing and maintaining infections through modulation of the body's immune system.

BIT225 is Biotron's lead antiviral clinical-stage, investigational, small molecule antiviral drug. It is an oral drug, suitable for once-a-day dosing and has a well characterised safety profile. The drug has been evaluated in nine clinical trials involving healthy volunteers, patients with HIV-1 infection, patients co-infected with Hepatitis C virus (HCV) and HIV-1 and patients with HCV (as monotherapy and in combination with pegylated interferon-alfa and ribavirin). Formal pre-clinical studies have assessed safety over 24 weeks of dosing.

Recently the Company commenced two Phase 2 HIV-1 trials in Australia and Thailand to assess the impact of BIT225 on the HIV-1 reservoir and key markers of improved health outcomes.

Biotron is now in discussions with its USA advisors and consultants to expedite progression of BIT225 into human trials for treatment of SARS-CoV-2 infection. The Company has sufficient drug product on hand after recently completing the manufacture of several kilograms of additional clinical grade (cGMP) drug.

The Chair of Biotron's Scientific Advisory Board, Professor Rob Murphy, Professor of Medicine and Biomedical Engineering, John P. Phair Professor of Infectious Diseases at Northwestern University, Chicago, said, "These very encouraging results in a SARS-CoV-2 animal model demonstrate a robust antiviral response that justifies further study in humans. BIT225 is a novel antiviral drug that has been safely used in over 200 patients with other RNA viral diseases including HIV and hepatitis C. This is drug that should be studied as a COVID19 treatment in the very near future."

Biotron's Managing Director, Michelle Miller, said "These results suggest that BIT225 may have benefit over other known antiviral agents. We will actively pursue all avenues to progress this Biotron drug into human trials as quickly as possible."

This announcement has been approved for release by the Company's Managing Director.

About Biotron

Biotron Limited is engaged in the research, development, and commercialisation of drugs targeting significant viral diseases with unmet medical need. The Company has BIT225 in clinical development for HIV-1 and promising preclinical programs for SARS-CoV-2 and HBV. In addition, Biotron has several earlier stage programs designing drugs that target a class of virus protein known as viroporins which have a key role in the virus life cycle of a very broad range of viruses, many of which have caused worldwide health issues such as Coronavirus, Dengue, Ebola, Middle East Respiratory virus, Influenza and Zika viruses.

Enquiries

Dr Michelle Miller Managing Director Biotron Limited+61-(0)412313329mmiller@biotron.com.au^[1]

Rudi MichelsonMonsoon Communications+61-3 9620 3333

View original content:https://www.prnewswire.com/news-releases/biotron-drug-effective-against-covid-19-in-animals-301432000.html^[2]

References

1. ^{^} mmiller@biotron.com.au (www.prnasia.com)
2. ^{^} https://www.prnewswire.com/news-releases/biotron-drug-effective-against-covid-19-in-animals-301432000.html (www.prnewswire.com)