Biotron - Novel Small Molecule Antiviral Therapeutics

The Company’s core expertise lies in designing and developing new drugs that target a new class of viral proteins known as viroporins. Viroporins are found in a range of viruses, and include the p7 protein of HCV, Vpu protein of HIV-1, M2 protein of Influenza, and M protein of Dengue virus.  These small hydrophobic proteins are assembled into oligomeric ion channels. Viroporins play key roles in viral pathogenesis, and are essential to the virus life cycle, which makes them ideal drug targets.

Biotron’s lead drug, BIT225, is in Phase 2 clinical development for treatment of both HIV-1 and HCV.

For HIV-1, BIT225 offers the potential to eradicate reservoirs of virus found in long-lived macrophage cells, which contribute to the need for life-long treatment with antiretroviral drugs. Eradication or cure of HIV-1 infection remains the holy grail of HIV-1 treatment strategies.

For HCV, BIT225 offers potential as a new class of oral direct-acting antiviral (DAA) drug that may be used in combination with other new classes of DAAs, offering future treatment options within the complex field of HCV treatment strategies.

In addition to its clinical stage programs for BIT225, Biotron has early stage programs targeting emerging viruses with significant health and economic impact, such as Zika and Dengue.

BIT225 is in mid‑stage clinical development for treatment of HIV-1 and Hepatitis C virus (HCV) infections, with seven clinical trials completed. BIT225 has been dosed in 55 healthy human volunteers and 94 subjects infected with either HIV-1, HCV or co-infected with HIV-1/HCV.

Clinical trial results for BIT225 include:

HIV-1

• BIT225 is a novel first-in-class HIV-1 Vpu protein inhibitor with the aim of inhibiting virus replication in cellular reservoirs.
• In vitro studies have shown BIT225
  • Significantly inhibits HIV-1 release in a dose dependent manner from CD14+ and CD16+ monocyte subsets at various stages of differentiation and monocyte-derived dendritic cells (MDDC)
  • Significantly reduces cell-cell transmission of virus from HIV-1 infected myeloid lineage cells to CD4+ T cell targets
  • Has broad spectrum activity against clinical isolates from different virus clades and selected drug resistant strains
  • Has additive or synergistic inhibition of virus replication in combination with marketed HIV-1 anti-retroviral drugs from different classes
• Studies in the clinic have demonstrated
  • BIT225 treated isolated cells from HIV-1 infected patients show reduced HIV-1 release from CD14+ monocytes
  • Following 10 days of monotherapy in HIV-1 infected patients, BIT225 can reduce viral copy numbers and inhibit replication in myeloid lineage cells (including dendritic cells)
  • BIT225 may impact on macrophage associated immune activation
  • BIT225 is able to cross the blood-brain barrier, with potential to treat HIV-associated neurocognitive disorder (HAND)

HCV

• BIT225 is a novel first-in-class viral assembly inhibitor that targets HCV p7 protein
• In vitro studies have shown
  • Pan genotypic activity in HCV infectious clone assay
  • Synergy with marketed drugs for the treatment of HCV
  • High barrier to antiviral resistance
• Studies in the clinic have demonstrated
  • Clinical antiviral efficacy against HCV genotypes 1 and 3
  • BIT225 treatment is associated with faster viral clearance in treated HCV patients
  • Substantial safety, tolerability and pharmacokinetic data in both Phase 1 and 2 clinical trials of up to 3 months dosing duration

Completed Human Clinical Trials:

• BIT225-001 – Phase 1, single-dose, dose escalating study (n=48)
• BIT225-003 – Phase 1b, HCV-infected patients (n=18)
• BIT225-004 – Phase 1b/2a, HIV-1  infected patients (n=21) Trial registration on ANZCTR
• BIT225-005 – Phase 2a, HCV-infected patients (n=24) Trial registration on ANZCTR
• BIT225-006 – Phase 2, HIV/HCV co-infected (n=12) Trial registration on ANZCTR
• BIT225-007 – Phase 1 capsule formulation, cross-over study (n=14) Trial registration on ANZCTR
• BIT225-008 – Phase 2, repeat dose (n=60) Trial registration on ANZCTR

In addition to the development of BIT225, Biotron has a portfolio of preclinical antiviral programs developing drugs targeting a range of significant established and emerging viral diseases such as Dengue, Zika and Influenza virus.

Viroporins are encoded by many viruses and are essential for pH-dependent viral uncoating and/or assembly of infectious virus. Their role in viral pathogenesis supports their essential role in the virus life cycle, making viroporins ideal targets for therapeutic intervention.

Biotron’s unique approach to designing, screening, and developing small molecules that work against viroporin proteins enables the targeting of a wide range of viral disease; examples include:

• Influenza (in particular resistant strains)
• Dengue virus
• Zika Virus
• Ebola and SARs

Clinical studies with BIT225 have demonstrated the robustness of Biotron’s approach providing strong validation of safety & efficacy of targeting viroporins.