Today, Resverlogix’s Chief Scientific Officer Dr. Norman CW Wong is presenting data on RVX-208 at the Arteriosclerosis, Thrombosis and Vascular Biology (ATVB) Scientific Sessions 2015 in an abstract entitled: Effects of RVX-208 a selective bromodomain extra-terminal (BET) protein inhibitor beyond raising ApoA-I/HDL. Dr. Wong is also presenting tomorrow at a satellite conference in a presentation entitled: BET inhibition in lowering CVD risks.
Dr. Wong stated this morning, “We were very pleased to report at the ATVB on our data regarding the novel actions of RVX-208 in both humans and at the molecular level. The information presented adds new knowledge to the field of ‘selective BET inhibition’ and how such activity may have a beneficial effect in lowering CVD risks in a population with atherosclerotic disease and high residual risks of major adverse cardiac events (MACE) despite treatment with current standard of care therapy. The data presented tells us that RVX-208 appears to have effects on cellular pathways that play important roles in atherosclerosis.”
Both presentations detail the actions of RVX-208 in raising ApoA-I protein production and thereby promote de novo synthesis of more functional HDL particles. Equally important, RVX-208 affects cellular pathways with known roles in lowering CVD risks beyond ApoA-I/HDL. Our lead compound is unique amongst the known BET inhibitors in clinical development because RVX-208 has the ability to selectively block the second ligand binding domain in BET proteins. This action is different from all other compounds in clinical development that are classified as pan-inhibitors which block both ligand binding domains in BET proteins with equal strength. The beneficial actions of RVX-208 in addition to ApoA-I comes from continued analysis of data collected from almost 1000 patients in our numerous clinical trials over the last 8 years. In the trials lasting more than 3 months, we noted that patients given RVX-208 had the expected rise in ApoA-I/HDL leading to lower major adverse cardiac events (MACE) but the magnitude was much more than anticipated. This observation suggested that RVX-208 had actions beyond its lipid effects. In order to look for new actions of RVX-208, we used microarray techniques to survey changes in gene activity after treating cultured human liver and whole blood cells with RVX-208. In brief, the actions of the compound had beneficial effects on pathways including that of: complement, coagulation, inflammation, cholesterol synthesis, and glucose metabolism. All of these pathways have known roles in the pathogenesis of atherosclerotic disease.
On Monday, April 27, Resverlogix announced a combination licensing and equity arrangement with Shenzhen Hepalink Pharmaceutical Co. that could represent in excess of US$400 million. Since then, Resverlogix is being covered by several reporters, including BioCentury, BioWorld Today, Bloomberg News, BioSpace Breaking News, Fierce Biotech and GEN News Highlights.
Zacks Small-Cap Research initiated coverage on Resverlogix on April 20, 2015. The report entitled: “RVX: Initiating Coverage of Resverlogix Corp.; A Clinical Stage Cardiovascular Company with an Epigenetics Platform,” published today by Jason Napodano, CFA and Nisha Hirani, MD.
Yesterday, Resverlogix was featured in the “Life Science Leader – Companies to Watch” by Wayne Koberstein, Executive Editor @WayneKoberstein.
“This 14-year-old company patiently stacks up clinical evidence of health benefits gained from oral treatments with a new, epigenetic MOA (mechanism of action) for long-neglected, large-market chronic diseases.”
The American College of Cardiology Annual Scientific Session and Expo is one of the most important cardiology conferences. Each year, interesting news is announced and scientific findings are presented over the course of three days. This year’s conference was held in San Diego on March 14-16. Periodically, Resverlogix will blog on topics held at major conferences.
The final presentation of the first day detailing the state of the art in vascular biology was delivered by Dr. Jorge Plutzky, associate professor at Harvard Medical School and director of the Vascular Disease Prevention Program. He presented his work on the role transcription factors play in determining cardiovascular disease (CVD) risks in patients with diabetes mellitus (DM). He showed data pointing to the role of both the peroxisome proliferator-activated receptors (PPAR) and retinoid X receptor (RXR) as the coordinators of cell signaling that enables blood vessel damage in patients with diabetes and CVD. Blood vessel damage is one of the first stages in development of cardiovascular disease and this damage can eventually lead to events like heart attacks and strokes.
In the last segment of his presentation Dr. Plutzky detailed how epigenetics may be responsible for coordinating a multitude of genes leading to the development of vascular disease. He described how pro-inflammatory signals rapidly activate specific intracellular proteins, which in turn can lead to blood vessel disease. He also described the role of bromodomain extra-terminal (BET) proteins and specifically BRD2 in blood vessel disease. He noted that use of a BET inhibitor reduced markers for CVD in an animal model of DM, opening new possibilities for use of epigenetic drugs in the treatment of people with CVD and DM.
Dr. Norman CW Wong, CSO of Resverlogix presented data on RVX-208 at the European Atherosclerosis Society (EAS) annual meeting in an oral abstract entitled: “RVX-208 a selective bromodomain extra-terminal protein inhibitor reduces MACE in patients with high residual risks of cardiovascular disease, a post-hoc analysis”.
Resverlogix’s Phase 2b clinical trials SUSTAIN and ASSURE revealed that treatment with RVX-208 lead to a marked reduction in major adverse cardiac events (MACE). The addition of RVX-208 (200 mg/day) on top of standard of care therapy including optimal doses of statins in SUSTAIN and ASSURE raised levels of ApoA-I/HDL-c in treated patients.
These changes alone are unlikely to explain the observed MACE reduction. In the search for potential explanations, levels of more than 60 plasma biomarkers were measured in clinical samples collected in the two trials. One of the significant findings was that RVX-208 lowered glucose in patients with diabetes mellitus (DM) who also had low levels of HDL. This finding is intriguing because there are many patients with DM who have low HDL and high CVD risk thus they would benefit from the actions of RVX-208. Furthermore, this glucose lowering action of RVX-208 goes hand in hand with the preliminary observations from our recent trial of subjects with pre-diabetes mellitus completed in Australia.
The presentation also included state-of-the-art microarray data. This technology is a powerful approach to look at how RVX-208 may be beneficial for CVD beyond that provided by biomarker measurements. The technology allows us to analyze and survey thousands of genes for effects of RVX-208. The data collected from primary human hepatocytes showed that RVX-208 attenuated activity of genes in cellular pathways or networks for inflammation, coagulation, complement, cholesterol synthesis and glucose metabolism.
This data reflects our leadership role in understanding selective BET inhibition by RVX-208 in both humans and at the cellular level. The marked reductions of MACE in SUSTAIN and ASSURE provides the foundation for the Company’s planned Phase 3 clinical trial called BETonMACE. The microarray data is most exciting because it provides, at a cellular level, novel insights that detail the multiple activities of RVX-208 beyond its ApoA-I effects in lowering MACE.
Today Resverlogix was featured in BioSpace Breaking News: EXCLUSIVE: Resverlogix Corporation (RVX.TO) CEO Says Experimental Cardiac Drug Holds High Hopes, As Biotech Booms, reportedby Riley McDermid, Breaking News Sr. Editor, BioSpace.
Here is an excerpt from the article:
“The boom in the biotech sector has been uplifting to the entire industry,” said McCaffrey. “The goal of the industry is to help patients and to treat diseases more effectively and with less toxicities. The more research, the higher the level of understanding about the biology behind diseases, the better our medicines will be.”
A new analyst report has been published covering the cost benefits of RVX-208 and discussing our single epigenetic target with effects on multiple synchronized biological pathways.
Marcel Wijma, chief research analyst at Van Leeuwenhoeck Research (VLR) initiated coverage on Resverlogix on March 16, 2015 in a new report entitled: “Epigenetics & Select BET Inhibition. A new approach to high risk diabetes and chronic kidney disease.” Contact info: email@example.com