Biotron has developed a program of identification, characterization and pre-clinical evaluation of small molecular compounds that inhibit a new class of antiviral targets known as "viroporins" . Through blocking the ion channel activity of viroporins, these compounds are able to inhibit viral budding and replication. Viral proteins targeted under Biotron's Virion program include Vpu of Human Immunodeficiency virus type 1 (HIV-1), p7 of Hepatitis C virus (HCV), M protein of Dengue virus and E protein of coronaviruses including Sudden Acute Respiratory Syndrome (SARS) coronavirus.

Biotron has achieved the following milestones:

  • Awarded A$1.7m START grant from Australian Federal government for preclinical development of HIV-Vpu inhibitor.
  • Awarded A$250,000 Biotechnology Innovation Fund grant from Australian Federal government for proof-of-concept studies relating to viruses other than HIV.
  • Identified new antiviral targets suitable for therapeutic intervention, including Vpu (HIV-1), p7 (HCV), M protein (Dengue virus), E protein (SARS and other coronaviruses).
  • Rationally designed, synthesized and screened a targeted library of novel small molecule inhibitors of these viral proteins.
  • Developed proprietary rapid, high throughput bacterial cell assays for screening against these targets.
  • Confirmed antiviral activity of hits in relevant in vitro cell-based antiviral assay systems.

HIV-1

The HIV/Vpu program is the most advanced, with a lead compound currently in preclinical safety tests. Vpu represents a new drug target in the fight against HIV. The protein plays an important role in the budding and release of newly formed viruses from infected cells, a process that is crucial for the progression of infection.

Existing HIV therapeutics are directed at one of three stages in viral replication: reverse transcription, protease activity and receptor binding to facilitate viral entry into the host cell. As a result of the limited range of drug targets, the emergence of drug resistant viral strains has become a significant issue. By blocking a new pathway in HIV infectivity, Vpu inhibitors have the potential to combat drug-resistant viral strains, in combination with highly active antiretroviral therapies (HAART) and in monotherapy.

Biotron's Vpu inhibitors differ to existing therapies in that they are particularly effective against monocytes and macrophages, both of which are cell types that current regimens of HAART fail to target successfully. Recent research has highlighted the importance of these cells in HIV infection by demonstrating that they can act as reservoirs of virus in HIV-infected individuals.

Phase I/IIa clinical trials for Biotron's lead HIV therapeutic will be initiated at the conclusion of preclinical safety tests.

Biotron has achieved the following milestones in its HIV antiviral program.

  • Undertaken a lead optimization program for the HIV project and identified lead candidates for further development.
  • Undertaken preliminary preclinical tests on HIV lead candidate including acute toxicity, pharmacokinetic studies, in vitro metabolism, chemical stability, receptor hit screening, etc – demonstrated good levels of bioavailability, good metabolism profiles, good stability following oral dosing.
  • Selected a leaad compound, BIT25, to progress into further preclinical and clinical development.
  • Commenced GLP preclinical safety studies with HIV lead candidate.
  • Identified sites for Phase I/IIa clinical trial for HIV therapeutic and is discussion with regulatory authorities.

Hepatitis C Virus

Biotron has designed and tested over 250 compounds in its Virion antiviral program, and is currently screening these compounds for activity against Hepatitis C virus (HCV) p7 protein, with the aim of identifying a lead candidate. A research collaboration has been established with the Hepatitis Laboratory at the Burnet Institute, Australia to further characterize p7 as an antiviral target.

Biotron has achieved the following milestones in its Hepatitis C antiviral program.

  • Identified several lead candidates targeting HCV-p7 and commenced a lead optimization program.
  • Developed rapid bacterial cell-based assay to screen against this target.
  • Developing surrogate mammalian-cell based infectivity assay for HCV.

Other Viruses

Biotron has been able to demonstrate that its Virion technology has the potential to treat other viruses such as the SARS coronavirus, Dengue virus and a wide range of other virus-related diseases. Antiviral testing against a broad range of diseases is currently underway in conjunction with researchers at the National Institute of Health (NIH) in the USA.

Macrophages are important in HIV replication

Macrophages have been shown to act as virus "reservoirs" in vivo, and have the ability to spread virus particles to bystander CD4 lymphocytes. These cells are the most important target of HIV in the central nervous system. This highlights the importance of macrophages in the pathogenisis of HIV infection and strongly supports the clinical relevance of Biotron's strategy to interfere with HIV replication in macrophages.

Biotron's compounds inhibit release of HIV from infected macrophages

Biotron's compounds inhibit budding or release of HIV from infected macrophages, preventing the virus from spreading throughout the body.

PRODUCT DEVELOPMENT

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Virion

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