Abivax announced that it has published new data characterizing the novel mechanism of action of its lead drug candidate, ABX464 in NatureScientific Reports, a prestigious, highly rigorous peer-reviewed scientific journal. The research, entitled “Both anti-inflammatory and antiviral properties of novel drug candidate ABX464 are mediated by modulation of RNA splicing,” concludes that ABX464’s ability to selectively upregulate anti-inflammatory miR-124 and selectively splice viral RNA, but not endogenous cellular RNA, may have applicability for treatment of both inflammatory diseases and HIV infection. The research, conducted in the cooperative ABIVAX-CNRS laboratory directed by Prof. Jamal Tazi, demonstrated that ABX464 enhances the splicing of HIV RNA in infected peripheral blood mononuclear cell (PBMCs) from healthy individuals, and enhances the expression and splicing of a single long noncoding RNA to generate the anti-inflammatory miR-124 in patients. The data further demonstrate that ABX464 binds to an mRNA-binding protein complex known as the cap binding complex (CBC) and enhances its functioning, resulting in the enhanced splicing of two types of RNA: 1.) a segment of HIV RNA which the HIV virus needs in an unspliced form for replication, thus inhibiting replication; and 2.) a long non-coding human RNA (lncRNA 0599-205), which, upon splicing results in specific increased expression of miR-124, a microRNA with potent anti-inflammatory properties. MicroRNAs are known to dampen gene expression, and miR-124 is known to specifically downregulate the expression of a number of pro-inflammatory cytokines, thereby mitigating inflammation. Furthermore, by binding to CBC, ABX464 reinforces the biological functions of CBC in cellular RNA biogenesis including splicing, which is especially important in tissues suffering from perturbations, like inflammation. Therefore, the molecule acts inside injured immune cells to preserve the integrity of newly synthesized RNA. Importantly, ABX464 did not modulate the rate of splicing of cellular genes, a key requirement for a safe and well tolerated drug. ABX464 is a first-in-class small molecule for oral administration that has been tested in Phase 2a clinical trials for ulcerative colitis (UC) and HIV infection. In the proof-of-concept clinical trial in UC patients, ABX464 statistically significantly improved UC signs and symptoms on both clinical and endoscopic endpoints, achieving a clear and clinically meaningful magnitude of effect in a small exploratory study. Based on these data, Abivax is currently preparing the imminent regulatory submission of a phase 2b clinical trial in 232 ulcerative colitis patients, as well as phase 2a proof-of-concept studies for two additional inflammatory indications, Crohn’s disease and rheumatoid arthritis.