RVX-208 the first selective bromodomain extra-terminal (BET) protein inhibitor being developed for patients with high residual risks of cardiovascular disease
SAN DIEGO, CA/CALGARY, AB, March 16, 2015 /CNW/ - Resverlogix Corp. (TSX:RVX) (the "Company") today announced that Dr. Jan Johansson, senior vice president of medical affairs at Resverlogix presented new data on RVX-208 at the prestigious ACC.15 Scientific Sessions in San Diego, CA in a poster entitled: "RVX-208 the first selective bromodomain extra-terminal (BET) protein inhibitor being developed for patients with high residual risks of cardiovascular disease".
RVX-208 is an orally active small molecule that interacts selectively with the second ligand binding domain present in BET proteins. RVX-208 inhibits these proteins from binding to the natural ligand acetylated lysine, found in the tail of histone proteins. This interaction modulates the structure of chromatin which in turn leads to altered activity of selected genes. This is the epigenetic mechanism by which RVX-208 increases production of ApoA-I the dominant protein in high density lipoproteins (HDL). Recent analysis of pooled data from Phase 2b clinical trials SUSTAIN and ASSURE (n=499 over 6 months) revealed a marked 55% (p=0.02) relative risk reduction (RRR) in major adverse cardiac events (MACE) for the entire population with a more pronounced effect of -77% RRR (p=0.01) in those with diabetes mellitus (DM).
To better understand how RVX-208 may reduce MACE, levels of more than 60 biomarkers were collected in the aforementioned trials. In addition, cellular information was gathered using microarray technology.
Biomarker analysis from the SUSTAIN and ASSURE trials revealed significant changes between RVX-208 vs. placebo (change, p value) in: serum alkaline phosphatase (-6 U/L, <0.0001), HDL-c (+3 mg/dL, <0.001), ApoA-I (+7.5 mg/dL, <0.01), large HDL (+0.7 umol/L, <0.05), HDL size (+0.1, <0.05), and total HDL particles (+1.8 umol/L, <0.1). While these findings were evident in all patients, two groups appeared to benefit more from RVX-208 were those with DM or chronic kidney disease (CKD). In those with DM (n=192) given RVX-208, glucose was unchanged vs. a non-significant (p<0.1) rise of +0.7 mmol/L in placebo patients. In those with DM (n=119) and low HDL <40 mg/dL, RVX-208 reduced glucose significantly (p<0.01) by -0.3 mmol/L while in placebo the glucose increased +0.9 mmol/L. In CKD subjects (n=48) with mild to moderate renal failure (eGFR <60 mL/min/1.73m2) given RVX-208 vs placebo there was a +3.4% vs. -5.9% in eGFR, respectively.
The microarray studies were performed using primary human liver cells exposed to RVX-208. This treatment demonstrated significant changes in cellular pathways or networks characterized by: an attenuation in inflammation, coagulation, complement and cholesterol synthesis.
Dr. Jan Johansson stated, "We are very excited to report this new preliminary data that significantly extends our knowledge of RVX-208 activity in both humans and at the molecular level. As we continue to analyze the wealth of data collected in our human trials of RVX-208, it offers unique insights into the profile of selective BET inhibition. These clinical findings tell us the effects of RVX-208 on ALP, HDL profile, glucose and eGFR in better understanding how BET inhibition may lower MACE. 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. We will utilize this new knowledge in conducting our proposed Phase 3 clinical trial entitled BETonMACE."
RVX-208 is a first-in-class, small molecule selective BET bromodomain inhibitor. BET bromodomain inhibition is an epigenetic mechanism that can turn disease-causing genes off, returning them to a healthier state. RVX-208 is the first and only BET inhibitor selective for BRD4-BD2, producing a nexus of biological effects with potentially important benefits for patients with diseases such as cardiovascular disease (CVD), diabetes mellitus (DM), Alzheimer's disease, peripheral artery disease, and chronic kidney disease while maintaining an excellent safety profile. Resverlogix is planning to study RVX-208 in a proposed Phase 3 clinical trial in CVD patients with DM and low HDL.
Resverlogix Corp. is developing RVX-208, a first-in-class, small molecule selective BET bromodomain inhibitor for the treatment of patients with cardiovascular disease, diabetes mellitus, Alzheimer's disease, peripheral artery disease, and chronic kidney disease. RVX-208 is the only selective BET bromodomain inhibitor in clinical trials. Resverlogix's common shares trade on the Toronto Stock Exchange (TSX: RVX). For further information please visit www.resverlogix.com. We can be followed on our blog at http://www.resverlogix.com/blog and via Twitter @Resverlogix_RVX.
This news release may contain certain forward-looking information as defined under applicable Canadian securities legislation, that are not based on historical fact, including without limitation statements containing the words "believes", "anticipates", "plans", "intends", "will", "should", "expects", "continue", "estimate", "forecasts" and other similar expressions. In particular, this news release includes forward looking information relating to research and development activities and the potential role of RVX-208 in the treatment of cardiovascular disease, Alzheimer's disease, peripheral artery disease and chronic kidney disease. Our actual results, events or developments could be materially different from those expressed or implied by these forward-looking statements. We can give no assurance that any of the events or expectations will occur or be realized. By their nature, forward-looking statements are subject to numerous assumptions and risk factors including those discussed in our Annual Information Form and most recent MD&A which are incorporated herein by reference and are available through SEDAR at www.sedar.com. The forward-looking statements contained in this news release are expressly qualified by this cautionary statement and are made as of the date hereof. The Company disclaims any intention and has no obligation or responsibility, except as required by law, to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.
For further information, please contact:
Donald J. McCaffrey
President and CEO
Director, Investor Relations & Corporate Communications
Tony Russo, Ph.D.
Matt Middleman, M.D.
Russo Partners, LLC
Phone: 212 845 4251
SOURCE Resverlogix Corp.