US Markets closed on Monday May 27th for Memorial Day. Resverlogix presents at European Atherosclerosis Society (EAS) 2019 Congress on Monday May 27th (see abstract below). The keynote speaker is Paul Ridker, a leader in the field of inflammation as a cardiovascular risk factor, also gives his talk on Monday.

Also, if you missed these two Resverlogix posters from Vascular Discovery that further discuss the anti-inflammatory effects of apabetalone, here you go:

Vascular Discovery 2019 Poster #1: Apabetalone (RVX-208) inhibits key pro-atherogenic mediators and pathways in diabetes and inflammatory conditions; in vitro and in patients

Vascular Discovery 2019 Poster #2: Hepatic Expression of C-Reactive Protein is Epigenetically Regulated by BET Proteins and Inhibited by Apabetalone (RVX-208) in Vitro and in CVD Patients

Apabetalone SMASH inflammation! Here is the EAS poster abstract that will be presented on Monday May 27th.

APABETALONE (RVX-208) ATTENUATES INFLAMMATORY MILIEU UNDERLYING ADHESION OF MONOCYTES TO ENDOTHELIAL CELLS IN TYPE 2 DIABETES MELLITUS WITH CARDIOVASCULAR DISEASE PATIENTS

Background and Aims: To explore mechanisms behind the 57% relative risk reduction of major adverse cardiovascular events (MACE) in patients (pts) with type 2 diabetes mellitus (T2DM) and CVD given 200 mg apabetalone (APL, RVX-208, inhibitor of bromodomain and extra-terminal [BET] proteins that are epigenetic readers of histone acetylated lysine).

Methods: SOMAscan proteomics of patient plasma given APL (n=25) or placebo (n=30) and cultured monocyte (THP-1) or endothelial (HUVEC) cells.

Results: Plasma proteomics from CVD+/-T2DM pts given APL or placebo showed changes in 4 well-known pathologic pathways and inflammation triggered by TNFa underpinning CVD. Proteins induced by TNFa (p<0.001; z-score = 2.270) were attenuated by APL (p<0.001; z-score = -2.308). To replicate this inflammatory milieu, TNFa (10 ng/ml) or high glucose (HG, 25.6 mM) was added to co-cultures of THP-1 and HUVEC leading to enhanced adhesion 12- and 2.4-fold, respectively but inhibited by APL (44-32%). Very Late Antigen-4 (VLA-4) a THP-1 adhesion mRNA rose 1.3-fold in HG and APL suppressed it >50%. Similarly, E-selectin, MCP-1, and MYD88 mRNAs that mediated adhesion rose by 2-, 2- and 1.3-fold, respectively in HUVECs exposed to HG while APL attenuated (30-90%). Furthermore, Nanostring data from HUVECs showed HG induced many inflammatory genes underlying CVD but APL blocked ~90% of these. Gene Set Enrichment and functional Gene Ontology Analysis showed many inflammatory and immunoregulatory genes were positively impacted by HG but negatively affected by APL.

Conclusions: APL lowers MACE in T2DM and CVD pts by attenuating monocyte adhesion to endothelial cells and thereby possibly reducing atheroma formation.