Clinical Trials

Date: 2016-12-10

Type of information: Presentation of results at a congress

phase: preclinical

Announcement: presentation of results at HIV DART (Frontiers in Drug Development for Antiretroviral Therapy) scientific conference

Company: Abivax (France)

Product: ABX464

Action mechanism: splice modulating agent. ABX464 is a first-in-class, small molecule inhibiting HIV replication through the inhibition of the Rev protein activity and modulation of RNA splicing. In collaboration with the team of Professor Jamal Tazi at the CNRS in Montpellier, France, Abivax designed ABX464 to lead to a clinically relevant improvement in HIV therapy. Preclinical data in humanized mice demonstrated that ABX464 monotherapy had an antiviral effect that was sustained following treatment interruption (Campos et al, Retrovirology 2015 12:30). A prior food-effect study demonstrated a three-fold increase in parent drug exposure when administered with food, without a significant impact on active glucuronide metabolite.

Disease: HIV/Aids

Therapeutic area: Infectious diseases

Country:

Trial details:

Latest news:

• • On December 8, 2016, Abivax announced  that the company presented new preclinical data on ABX464, ABIVAX’s first-in-class drug candidate for a functional cure of patients with HIV/AIDS, during this week’s HIV DART (Frontiers in Drug Development for Antiretroviral Therapy) scientific conference in Los Cabos, Mexico.
• The data show that in in vitro models, ABX464 exposure leads to a 50-fold upregulation of IL-22, a potent anti-inflammatory cytokine, by macrophages as well as a 10-fold upregulation of the anti-inflammatory microRNA miR-124 in T-lymphocytes. In addition, Abivax reported for the first time that in a preclinical model of colitis, treatment with ABX464 reduces macrophage recruitment into the intestine and also inflammatory cytokine release (IL-6 and TNFa), thereby preventing the histological changes of the gut associated with colitis.
• Furthermore, Abivax disclosed that after stopping the treatment, the protective effect of ABX464 in this disease model lasted for at least 6 weeks despite continued exposure to DSS, a substance well known to induce the pathological features of colitis. This therapeutic effect is mediated at least in part by IL-22, an anti-inflammatory cytokine known to regulate tissue repair and recovery from colon injury, as antibodies to IL-22 partly abolished this protection.
• Abivax’soral presentation, entitled,“Anti–HIV drug candidate ABX464 prevents intestinal inflammation by producing IL-22 in activated macrophages" was given by Prof. Jamal Tazi (Director, Institute for Molecular Genetics, CNRS and University of Montpellier, France and Executive Committee Member, Abivax) on Wednesday, 7. December during the session on ‘inflammation and cure’. “This newly discovered anti-inflammatory effect suggests that our lead compound, ABX464, may be able to modulate important disease parameters not only in HIV, but also in other inflammatory conditions like inflammatory bowel disease (IBD),” said Prof. Jamal Tazi, and Prof. Hartmut Ehrlich, M.D., CEO of ABIVAX added “We are rapidly responding to these encouraging new data. Abivax is planning to start a clinical proof-of-concept study of ABX464 to treat IBD during 2017.”
• • On October 27, 2016,  Abivax announced that the company presented new pre-clinical data on ABX464 for the treatment of patients with HIV/AIDS, during this week’s HIV Drug Therapy 2016 meeting in Glasgow, Scotland. ABIVAX’s presentation is entitled, “Differential effects of ABX464 and its primary metabolite ABX464-NGlc on HIV replication in human PBMC’s and macrophages: implications for treatment strategies to eliminate the reservoirs”. The data demonstrate that, while ABX464 is active against HIV replication in peripheral blood cells and also cultured macrophages, its primary metabolite, ABX464-N-glucuronide, is exclusively effective in preventing viral replication in cultured macrophages. Macrophages are part of the so called ‘reservoir’ where the virus hides during anti-retroviral treatment. Therefore, these cells are considered to be a critical source of viral rebound after stopping treatment. Given previous findings from Abivax’s completed Phase I and II clinical trials where ABX464-N-Glucuronide was shown to be present in human blood at concentrations exceeding those of ABX464 by more than 300-fold, these new data indicate that the primary target for the metabolite might be these reservoir cells, particularly as these are exposed to much higher concentrations of the metabolite.

Is general: Yes