BIT225 is in development as a novel first-in-class HIV-1 inhibitor with the aim of inhibiting virus replication in cellular reservoirs. It was designed to inhibit the ion channel activity of HIV-1 Vpu protein. Vpu is a well conserved protein that forms a virus ion channel and is involved in the assembly and release of infectious viral particles.

In vitro studies have shown that 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). It also significantly reduces cell-cell transmission of virus from all HIV-1-infected myeloid lineage cells to CD4+ T cell targets. BIT225 has demonstrated broad-spectrum activity against clinical isolates from among different virus clades and selected drug resistant strains, and additive or synergistic inhibition of virus replication in combination with licensed HIV-1 inhibitors from different antiviral classes in HIV-1 Ba-L infected macrophages, with no evidence of synergistic cytotoxicity with the drug concentrations evaluated.

Ex vivo, HIV-1 release from CD14+ monocytes isolated from HIV-1 positive subjects was reduced by treatment of the isolated cells with BIT225.

Results from a Phase 1b/2a 10-day monotherapy trial (BIT225-004) in HIV-1 positive subjects indicate that BIT225 can reduce viral copy numbers and inhibit replication in monocyte lineage cells, and preliminary data suggests that the drug may impact on macrophage-associated immune activation. In addition, the drug is able to cross the blood-brain barrier, opening up the potential to treat HIV-associated neurocognitive disorder (HAND).

Biotron is currently developing a synopsis for a phase 2 clinical trial with BIT225, to commence in 2016.

Combined with new or current drugs, BIT225 may provide a unique opportunity to significantly alter HIV-1 pathogenesis and disease progression.