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: http://www.resverlogix.com/upload/media_element/218/01/donald-mccaffrey-lsr-interview-8-26-15.pdf
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: http://www.thelifesciencesreport.com/pub/na/16701? utm_source=delivra&utm_medium=email&utm_campaign=TLSR+Final+7-1-15
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: http://www.resverlogix.com/upload/media_element/213/01/ebr_july-15_pp.76-79-resverlogix-corp.pdf
Here is a link to the full EBR Summer 2015 issue: http://www.samedanltd.com/magazine/12
We can also be followed on Twitter @Resverlogix_RVX
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.
Yesterday, Resverlogix posted a blog post (http://www.resverlogix.com/blog/2015/05/28/resverlogix-our-interest-in-chronic-kidney-disease/) 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.
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.
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.
United States Renal Data System (USRDS)
European Renal Association Conference
Final Programme (Abstract title on pg. 264)
American Diabetes Association (ADA): 75th Scientific Sessions
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
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.
April 27, 2015- BioCentury: Hepalink gains rights to Resverlogix’s RVX-208 in China. Link here: http://www.biocentury.com/dailynews/company/2015-04-27/hepalink-gains-rights-to-resverlogixs-rvx-208-in-china
April 28, 2015- BioWorld Today: Phase III Starting Soon. Resverlogix getting specific: With potential $400M BET, Hepalink licensing accord, by Randy Osborne. Link here to access the full article.
April 28, 2015- Bloomberg Business: Resverlogix in Discussions to Be Bought, by Eric Lam. Link here: http://www.bloomberg.com/news/articles/2015-04-28/resverlogix-ceo-says-company-in-discussions-to-be-bought
April 28, 2015- BioSpace Breaking News: Resverlogix (RVX.TO) CEO Says It’s in Talks With Suitors, After $100M in Q1 Deals, by Riley McDermid. Link here: http://www.biospace.com/News/with-almost-a-100-million-in-deals-for-q1/374186?source=sm&type=twitter_resverlogix042815
April 28, 2015- Fierce Biotech: Resverlogix gets a $116M China Drug development deal, stokes buyout buzz, by John Carroll. Link here: http://www.fiercebiotech.com/story/resverlogix-gets-116m-china-drug-development-deal-stokes-buyout-buzz/2015-04-28
April 28, 2015 – GEN News Highlights: Hepalink Buys China-Area Rights to Resverlogix’s CV Candidate for Up-to-$441.5M Link here: http://www.genengnews.com/gen-news-highlights/hepalink-buys-china-area-rights-to-resverlogix-s-cv-candidate-for-up-to-441-5m/81251205/
Donald McCaffrey, President and CEO of Resverlogix will appear live on BNN’s Business Day with Frances Horodelski on April 22 at 10:15 am ET. Tune in to watch the live interview!
Here is a link to the show Business Day: http://www.bnn.ca/Shows/Business-Day.aspx