Resverlogix Presents New Data at the ESC Congress 2015
News Sep 01, 2015
Resverlogix Corp. has announced that Dr. Norman Wong, chief scientific officer of Resverlogix Corp. presented new data at the European Society of Cardiology (ESC) Congress 2015 in a poster presentation titled: "RVX-208, an orally active BET inhibitor, lowers CVD risk by activities beyond raising ApoA-I/HDL."
The presentation summarizes studies designed to further understand the reductions in major adverse cardiovascular events (MACE) observed in patients with atherosclerotic disease given RVX-208 from the phase 2b trials called SUSTAIN and ASSURE. In order to identify the potential biologic processes underlying the benefit of RVX-208 in the study patients, primary human hepatocytes were exposed to RVX-208 and then changes in gene expression were surveyed using micro-array technology. This treatment caused decreases in the expression of many genes involved in cholesterol synthesis, fatty acid synthesis, innate immunity and glucose processing. Amongst the changes observed, RVX-208 decreased expression in 19 out of 26 genes that encoded components in the complement pathway.
Similarly, RVX-208 decreased expression in 20 out of 33 gene that encoded components within the coagulation cascade. Further support of the micro-array data that identified changes in gene expression by probing the messenger RNA (mRNA) levels was pursued by measuring specific proteins within the complement and coagulation cascade using plasma from SUSTAIN and ASSURE trials. Results showed significant decreases ranging from 7-12% vs. baseline in complement (i.e. complement factor 3) and coagulation components.
In additional studies, donor whole blood was exposed ex-vivo to RVX-208 followed by micro-array analysis enabling the identification of several pathways with known roles in atherogenesis including; pro-inflammatory signaling, cell-cell interactions and extracellular matrix organization. The actions of RVX-208 lowered atherogenesis by downregulating (8 of 11) pro-atherogenic genes but in contrast, upregulated (5 of 7) anti-atherogenic genes that control monocyte recruitment, migration and activation, macrophage function, inflammatory signaling and plaque stability.
Together, the new data from both primary human hepatocytes and whole blood suggest an overall anti-atherosclerotic benefit of RVX-208 that extends beyond its ApoA-I/HDL enhancing effects.
"Data summarized in the ESC presentation provide novel insights into the actions of RVX-208 also known as apabetalone. This molecule acts on epigenetics via bromodomain extra-terminal (BET) protein inhibition and it is the first member in the class of such compounds. Apabetalone affects multiple pathways including; anti-thrombotic, anti-atherosclerotic, and anti-inflammatory that may act in concert to reduce MACE in patients with CVD risk," stated Dr. Norman Wong. "Our findings described here provide valuable insights into the benefits of BET inhibition and are most timely as we embark on our Phase 3 clinical trial BETonMACE."
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