ABX-464

ABX-465 is an HIV anti-replicative agent.¹ It associates with the human cap-binding complex, a complex that processes pre-mRNA, and induces aberrant splicing in HIV pre-mRNA expressed from host-integrated viral DNA. It produces non-typical mRNA in primary peripheral blood mononuclear cells (PBMCs) from HIV-infected patients without disrupting normal cellular mRNA splicing when used at a concentration of 5 µM. ABX-465 increases the expression of the anti-inflammatory miR-124 in both uninfected and HIV-infected PBMCs at the same concentration. ABX-464 reduces the replication of seven HIV-1 mutant strains by 71-99% in HIV-infected primary PBMCs.² In vivo, ABX-465 (20 mg/kg per day) reduces HIV RNA levels and losses of CD4⁺, CD8⁺, and CD4⁺/CD8⁺ T cells in isolated peritoneal cells, as well as limits the extent of viral rebound, in a humanized mouse model of HIV infection. It also prevents weight loss and decreased colon length, increases in colon lesion number and size, and the number of macrophage infiltrates into colon tissue in a mouse model of ulcerative colitis induced by dextran sodium sulfate (DSS; Item No. 23250) when administered at a dose of 50 mg/kg per day.³

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1. Vautrin, A., Manchon, L., Garcel, A., et al. Both anti-inflammatory and antiviral properties of novel drug candidate ABX464 are mediated by modulation of RNA splicing. Sci. Rep. 9(1), 792 (2019).

2. Campos, N., Myburgh, R., Garcel, A., et al. Long lasting control of viral rebound with a new drug ABX464 targeting Rev - mediated viral RNA biogenesis. Retrovirology 12, 30 (2015).

3. Chebli, K., Papon, L., Paul, C., et al. The anti-HIV candidate Abx464 dampens intestinal inflammation by triggering IL-22 production in activated macrophages. Sci. Rep. 7(1), 4860 (2017).