First poster is now posted on the Resverlogix website. Click here for poster. The summary figure in the lower right portion of the poster is awesome. It encapsulates so many of the many steps of inflammation that are attenuated by apabetalone.

Apabetalone (RVX-208) inhibits key pro-atherogenic mediators and pathways in diabetes and inflammatory conditions; in vitro and in patients

Wednesday May 15: 407 - Apabetalone (RVX-208) Inhibits Key Pro-Atherogenic Mediators and Pathways in Diabetes and Inflammatory Conditions; in vitro and in Patients. Abstract available here.

"Apabetalone (RVX-208) is a small molecule bromodomain & extraterminal (BET) protein inhibitor that targets the second bromodomain (BD2) within BET proteins. In phase 2 trials, apabetalone treatment reduced relative risk of MACE events by 57% in patients with cardiovascular disease (CVD) and type II diabetes (T2DM). In both CVD and T2DM, elevated circulating glucose, inflammatory mediators, and cell surface adhesion molecules drive vascular inflammation (VI), resulting in the recruitment, adhesion, and infiltration of leukocytes to the atherosclerotic plaque. Continuous inflammation promotes cytokine production, immune cell infiltration, and plaque rupture, which accounts for 67% of fatal myocardial infarctions (MIs) and sudden cardiac deaths. Here we show in vitro that TNFα and high glucose treatment induced significant adhesion of THP-1 monocytes to endothelial cells, an outcome inhibited by apabetalone treatment. Apabetalone suppressed the transcription of critical drivers of pro-inflammatory signaling (RELA), immune cell activation and recruitment (MCP-1), and plaque rupture (IL-8) in endothelial cells. Ingenuity® Pathway Analysis (IPA®), GSEA, and GO analysis of human umbilical vein endothelial cell (HUVEC) gene expression data predicted that apabetalone would inhibit pro-atherogenic pathways, gene sets, and upstream regulators. These include cytokine and chemokine signalling, immune and inflammatory response, Toll-Like Receptor (TLR) signalling, and TNFα signalling. In addition, IPA® disease and biological function analysis predicted inhibition of immune cell recruitment and activation by apabetalone. These in vitro effects are consistent with plasma proteomic results (SOMAscan®) from apabetalone-treated CVD T2DM patients, which demonstrated inhibitory effects on TNFα signalling, acute phase response, intrinsic prothrombin activation, leukocyte extravasation signalling and coagulation. Amelioration of diabetes and inflammation driven atherogenesis by apabetalone treatment likely contributes to the reduction in MACE observed in phase 2. The ongoing phase 3 post-ACS clinical trial in T2DM patients, BETonMACE, is investigating the effect of apabetalone on MACE reduction and will report in 2019."