Resverlogix presents at the 2015 EASD annual meeting in Stockholm, Sweden

Today Dr. Norman Wong, Chief Scientific Officer of Resverlogix presented an oral abstract entitled ‘RVX-208 acts via an epigenetic mechanism to lower major adverse cardiovascular events (MACE) in patients with atherosclerosis and especially in those with diabetes mellitus’ at the annual meeting of the EASD held in Stockholm, Sweden.

The contents of the presentation detailed the continued efforts to understand the beneficial effects of RVX-208 (recently named apabetalone) on top of standard of care therapy in lowering MACE when given to patients with established cardiovascular disease (CVD). In previously completed Phase 2b clinical trials (SUSTAIN and ASSURE), post-hoc analyses showed that RVX-208 markedly reduced the combined MACE.

Our interest to understand the mechanisms by which RVX-208 reduces MACE in the trials comprised of patients with CVD and low levels of high-density lipoproteins (HDL) underlies the studies presented at the EASD. The data presented clearly showed the ability of RVX-208 to raise ApoA-I/HDL by enhancing production, but this effect of the compound was not sufficient to explain the observed reduction in MACE.  Therefore, several studies were undertaken to further explore the actions of RVX-208 in lowering CVD risk. Results of new studies involving the use of micro-array technology to survey gene expression in both liver cells and whole blood showed a number of pathways were affected by exposing them in vitro to RVX-208. These studies revealed that the compound affected specific pathways known to be important contributors to CVD risks including; complement, coagulation, inflammation, diabetes pathways, cholesterol synthesis and fatty acid synthesis. These pathways were not only acted upon by RVX-208 in a beneficial fashion but they were amongst the pathways most affected by the actions of the compound.  Of particular relevance to the EASD was the finding that in patients who had diabetes mellitus with established CVD and low HDL, RVX-208 use was associated with a serum glucose that was -0.3 mmol/L (n=76) lower while placebo was +0.9 mmol/L (n=43).  The absolute difference between the two groups was 1.2 mmol/L and this was significant with a p<0.01.

The results arising from our findings opened our eyes to the benefits of RVX-208, the first selective bromodomain extra-terminal (BET) protein inhibitor being tested for CVD risk reduction. The significance of the data is that this selective BET inhibitor has effects beyond its ability to enhance HDL production.  These unexpected actions of RVX-208 on several pathways that impact CVD risk provide potential biologic plausibility to why this compound may reduce MACE in the SUSTAIN and ASSURE trials.

New video of President & CEO Donald McCaffrey

At the recent Rodman & Renshaw 17th Annual Global Investment Conference, Donald McCaffrey, President & CEO had the opportunity to speak with Stock News Now (SNN). The video interview can be accessed here: Resverlogix also webcast from Rodman & Renshaw. The archived presentation can be accessed here:

Resverlogix is developing RVX-208 also named ‘apabetalone,’ a first-in-class, small molecule that is a selective BET bromodomain inhibitor. BET bromodomain inhibition is an epigenetic mechanism that can regulate disease-causing genes. Apabetalone is the first and only BET inhibitor selective for the second bromodomain (BD2) within the BET protein called BRD4. This selective inhibition of apabetalone on BD2 produces a specific set 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. Apabetalone is the only selective BET bromodomain inhibitor in human clinical trials. Resverlogix’s Phase 3 clinical trial BETonMACE in high-risk CVD patients with DM and low HDL is planned to commence in the fall of 2015. Resverlogix’s common shares trade on the Toronto Stock Exchange (TSX: RVX). For further information please visit We can also be followed on Twitter @Resverlogix_RVX

Resverlogix featured in The Life Sciences Report

Resverlogix is featured in today’s issue of The Life Sciences Report: “Disrupting Treatment of Cardiovascular Disease with Epigenetics: Resverlogix CEO Donald McCaffrey.” The full article can be accessed here:

Updated Resverlogix Website

We are pleased to share that Resverlogix has updated sections to the corporate website. Please look for updates to the Programs section as well as Presentations & Publications at

Please note that Resverlogix can also be followed on Twitter @Resverlogix_RVX and LinkedIn.

Resverlogix in The Life Sciences Report with Marcel Wijma

On Wednesday, July 1, Marcel Wijma, chief research analyst at Van Leeuwenhoeck Institute discussed Resverlogix and RVX-208 with Gail Dutton of The Life Sciences Report in Probe Biotech’s Diverse Subsectors For Strong, Undervalued Companies: Van Leeuwenhoeck’s Marcel Wijma.

Here is an excerpt from the article:

“The current, more innovative thinking is to reduce the risk of actually experiencing a heart attack. This new tactic, using epigenetics, is getting more emphasis from scientists and cardio specialists. The approach being developed by Resverlogix is a small molecule that can uncover the involved environmental and individual aspects of lifestyle that directly interact with the genome to influence epigenetic change in the DNA of a person. The company is targeting patients who have diabetes mellitus or chronic kidney failure who are at high risk for cardiovascular disease.

Resverlogix seems to have an interesting new way to deal with cardiovascular disease. With RVX-208, a first-in-class, small molecule, selective BET inhibitor, Resverlogix may have the answer to developing a new generation of cardio drugs.”

You can read the full article here: utm_source=delivra&utm_medium=email&utm_campaign=TLSR+Final+7-1-15

European Biopharmaceutical Review (EBR) Publication

Resverlogix’s Dr. Ewelina Kulikowski has written and published an article for the summer 2015 issue of the European Biopharmaceutical Review (EBR) titled, “New Direction.” The article focuses on how BET inhibition has an impact on multiple biologies with the potential to treat a variety of conditions such as cancer, inflammatory, neurodegenerative, metabolic and cardiovascular disorders.

Dr. Ewelina Kulikowski has been with Resverlogix for over 10 years and was recently appointed to Vice President of Scientific Development.

You can read “New Direction,” by Dr. Kulikowski here:

Here is a link to the full EBR Summer 2015 issue:

We can also be followed on Twitter @Resverlogix_RVX

Highlights from the ADA 75th Scientific Sessions 2015

Resverlogix’s scientists were in attendance at the American Diabetes Association (ADA): 75th Scientific Sessions June 5-9 in Boston. At the meeting there were major announcements in regards to diabetes mellitus (DM) and cardiovascular disease (CVD) in the late breaking trials section. Most people who suffer from DM die of CVD (68% over the age of 65). These two diseases are closely linked and the medical community is recognizing the significance and complexity of this relationship. In line with this connection, in 2008, the FDA provided a document called: “Guidance for Industry, Diabetes Mellitus — Evaluating Cardiovascular Risk in New Antidiabetic Therapies to Treat Type 2 Diabetes.”  The guidance requires that, since DM and CVD are so closely linked, any new drugs being developed for DM must undergo clinical trials to determine their effects in cardiovascular disease outcomes.

At the ADA there were two major sessions detailing recent clinical trials intended to ensure that new drugs on the market for treating DM were not raising CVD risks. Two trials called ELIXA and TECOS tested two members of the incretin class of drugs used to lower glucose in patients with DM. While ELIXA studied lixisenatide, an injected GLP-1 agonist being developed by Sanofi, the TECOS trial dealt with the actions of an oral dipeptidyl peptidase-4 inhibitor (DDP-IV) inhibitor saxagliptin from Merck. Both trials enrolled patients with DM and CVD to determine whether the addition of either of these agents on top of standard of care was better or worse in terms of CVD events.

The results of both trials were similar in that there was not an increase nor a decrease in major CVD events in response to lixisenatide or saxagliptin treatment on top of standard of care. This means that the treatments may be cardiovascular-safe in that they don’t increase the risk of cardiovascular events however they didn’t lower the rate of cardiac events either. The results point to the growing body of evidence revealing that drugs capable of effectively lowering glucose levels in patients with diabetes do not seem to be capable of lowering CVD risks.


Resverlogix: Further Interest in Chronic Kidney Disease

Yesterday, Resverlogix posted a blog post ( on CKD which garnered much interest on this topic. To further elaborate on the company’s interest; below we have references on several landmark studies focused on:

Alkaline Phosphatase and High Risk Vascular Disease
Alkaline phosphatase levels have been examined in several large landmark studies focused on high risk vascular diseases such as CKD, Diabetes, and CVD patients, as outlined below:

Chronic Kidney Disease (CKD)
Reported in the 2008 November issue of the Journal of the American Society of Nephrology, large epidemiological evidence revealed a consistent and robust association between a high blood level of alkaline phosphatase and cardiovascular death in thousands of dialysis patients across the United States.  The study which analyzed almost 74,000 hemodialysis patients during a three-year period found that patients with elevated alkaline phosphatase levels above upper limit normal (>120 IU/L) had a 25% higher death rate. According to the National Kidney Foundation, an estimated 26 million American Adults have Chronic Kidney Disease (CKD) in 2013. CKD is a progressive disease that usually starts with Type 2 Diabetes then proceeds to Chronic Kidney Disease, Dialysis and End Stage Renal Disease.

Diabetes & Metabolic Syndrome
In the 2011 article reported in The American Journal of Medicine, supported by the National Kidney Foundation, an observation study covering 15,234 adult participants observed a highly significant increase in serum alkaline phosphatase (ALP) in those patients with diabetes, stroke, metabolic syndrome and heart failure.     

Cardiovascular Disease
A 2012 prospective study, reported in Arteriosclerosis Thrombosis and Vascular Biology ATVB January 28, 2013, 3381 men aged 60-79 years of age without history of myocardial infarction or stroke were followed up for a period of 11 years during which there were 605 major CVD events (fatal coronary heart disease, nonfatal myocardial infarction, stroke and CVD death) and 984 total deaths. ALP was associated with increased risk of coronary heart disease in elderly men in the study.

As mentioned, Resverlogix is attending these two upcoming conferences: The European Renal Association – European Dialysis and Transplant Association (ERA-EDTA) to be held in London on May 28-31 and the American Diabetes Association (ADA): 75th Scientific Sessions being held from June 5-9 in Boston.

Resverlogix: Our Interest in Chronic Kidney Disease

Diabetes Mellitus (DM) is known to be the underlying cause for many long term health consequences. One of the most serious is chronic kidney disease (CKD). 40% of people suffering from DM will eventually develop CKD. CKD results from the long term effects of DM on blood vessels and the filtration apparatus (nephrons) of the kidneys. It is often referred to as a silent killer because it is insidious in onset, progressing slowly over many years and sometimes decades. According to the National Institute of Diabetes and Digestive and Kidney Diseases, more than 31 million people in the US (or 10% of the adult population) currently suffer from CKD.

Healthy kidneys filter metabolic by-products from the blood in order for these unwanted material to be components in the urine and thus eliminated from the body.. One important measure of kidney function is estimated glomerular filtration rate (eGFR) which assesses the amount of fluid the kidney can filter over a period of time. In patients with CKD, as kidney function declines, the eGFR decreases. Unfortunately for many patients, CKD can progress to a point when the kidneys fail completely. This is called end-stage renal disease (ESRD) and these patients require hemodialysis, often multiple times per week, in which a machine removes the metabolic waste products from the blood. The cost of ESRD and hemodialysis to the healthcare system is enormous, exceeding $34 billion each year in the U.S. The cost for one patient to be on dialysis for one year is almost $90,000.

The analysis of the data collected from previous clinical trials of RVX-208 tells us that patients with type 2 DM and low HDL-c when treated with RVX-208 and rosuvastatin appear to benefit the most in terms of lowering major adverse cardiac events (MACE). In patients with type 2 DM and mild to moderate CKD, as reflected by a reduced eGFR, treatment with RVX-208 seems to stabilize the CKD. Another important observation is that a biomarker called alkaline phosphatase (ALP), an enzyme that is produced in several tissue types, is lowered by the actions of RVX-208. This finding is significant because, in the CKD population, ALP is one of the best biomarkers of not only CVD but also total mortality.

In summary, RVX-208 appears to have multiple beneficial actions that result in a reduction in MACE in patients with DM and low HDL.

Resverlogix will be attending two upcoming conferences, The European Renal Association – European Dialysis and Transplant Association (ERA-EDTA) to be held in London on May 28-31 and the American Diabetes Association (ADA): 75th Scientific Sessions being held from June 5-9 in Boston. Stay tuned for upcoming Tweets from the conferences @Resverlogix_RVX.

External links:

United States Renal Data System (USRDS)

European Renal Association Conference

Final Programme (Abstract title on pg. 264)

American Diabetes Association (ADA): 75th Scientific Sessions

Resverlogix Presents at the ATVB Scientific Sessions in San Francisco, CA

Reporting from San Francisco, CA:

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.

Resverlogix is also on Twitter! Please follow us at: @Resverlogix_RVX