Progress on ABX464
Compound dampens intestinal inflammation by triggering IL-22 production in activated macrophages
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PARIS—ABIVAX, a biotechnology company targeting the immune system to eliminate viral diseases, recently announced the publication of a paper on its lead product candidate ABX464 in the July 7, 2017, online edition of Nature Scientific Reports. The paper, titled “The Anti-HIV Candidate ABX464 Dampens Intestinal Inflammation by Triggering Il-22 Production in Activated Macrophages” and authored by Prof. Jamal Tazi, et al., summarizes the experiments that explored the mechanisms by which ABX464 exerts its anti-inflammatory properties, as well as implications for potential therapeutic use in inflammatory bowel disease (IBD).
The new publication summarizes the in-vitro and in-vivo findings with ABX464 on reducing inflammation, as well as potential therapeutic implications. ABX464 was shown to stimulate the expression of the anti-inflammatory cytokine IL-22 in macrophages in preclinical testing.
In addition, ABX464 was shown to protect mice from the lethal effects of dextran sulfate sodium (DSS), which is an established animal model for experimental colitis. ABX464 treatment was not only critical for the survival of DSS-challenged mice, but also fully protected the histological structure of the murine intestine against changes induced by severe inflammation.
RNA profiling analysis showed that ABX464 induced the expression of IL-22, and this was demonstrated both in DSS-challenged mice as well as in in-vitro studies of LPS-stimulated bone marrow-derived macrophages. IL-22 is a cytokine that regulates tissue repair and recovery. The protective effect of ABX464 in these mice was substantially reduced by the simultaneous administration of antibodies to IL-22. ABX464 also showed a long-term protection against prolonged DSS-exposure after drug cessation. Furthermore, ABX464 reduced the colonic production of the pro-inflammatory cytokines IL-6 and TNFα and also the chemoattractant MCP-1.
“The results presented in this paper show for the first time that ABX464 specifically acts on the immune system to attenuate mucosal disease induced by DSS”, said Dr. Jamal Tazi, inventor of ABX464 and senior author of the paper. “ABX464’s ability to dampen intestinal inflammation in DSS-mice was clearly demonstrated. Additionally, its ability to reduce the inflammatory cytokines IL-6 and TNFα and induce the expression of IL-22 leading to tissue repair, and show long-lasting protective effects, is very promising.”
