ACC.15 Highlight, CVD & Epigenetics

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.

Further reading:
Brown et al. Molecular Cell (2014) 56: 219-231

Dr. Norman Wong presents at EAS Congress, Glasgow, Scotland

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.

Norman Wong Presentation at EAS Congress 2015

Resverlogix Exclusive in BioSpace Breaking News

Today Resverlogix was featured in BioSpace Breaking News: EXCLUSIVE: Resverlogix Corporation (RVX.TO) CEO Says Experimental Cardiac Drug Holds High Hopes, As Biotech Booms, reported by 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.”

You can read the full article here:
http://www.biospace.com/News/exclusive-resverlogix-corporation-ceo-says/369470

New Analyst Coverage on Resverlogix

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. “Based on our adjusted NPV valuation, we believe Resverlogix is substantially undervalued at the current share price of CAD 1.80. Using our valuation model, the Company’s current value is CAD 500 million, or CAD 5.85 per share. This represents an enormous upside from the current share price. The valuation is based on the development of its potential blockbuster RVX-208 and its purported early efficiency in reducing MACE.” The full initiation report can be found here: Leeuwenhoeck Research (VLR) Initiating Coverage Report – Resverlogix

Resverlogix 2015 Outlook: A Video Message from Donald McCaffrey, President & CEO

Thanks to the collaboration with Executive Video during the JP Morgan Annual Healthcare Conference last month in San Francisco, CA., we are able to provide a company overview and share our focus for 2015.

Resverlogix Corp. also presented on January 14 at Biotech Showcase 2015 during JP Morgan week. Click here to view the archived presentation.

For additional updates, please follow us on Twitter: @Resverlogix_RVX and YouTube: ResverlogixRVX 

Year in Review: Onwards & Upwards

Thank you for your continued support of Resverlogix over the last year! Drug development can be a rocky road but we are still going strong. This past year has been a whirlwind of events as we have had lots of progress with new data (77% relative risk reduction in MACE in patients with diabetes mellitus (DM)), the addition of Dr. Mike Sweeney to senior management and being featured in various publications/posters including: PNAS, Cell, PLOS One, Atherosclerosis, SciBX, ACC (Cleveland Clinic poster presentation), ESC (presented in ‘State of the Art and Featured Research Session’), and BioWorld Today (new article today!).

The company was able to identify the target patient population for our next clinical trial – patients with DM, established CVD and HDL-c less than 40mg/dL. Resverlogix is on track to commence this clinical trial in the first half of 2015! With the recent receipt of additional funding we are set to move forward.

Resverlogix on Twitter!

Starting off in the New Year, we will be entering the social media space – Twitter! You can follow us @Resverlogix_RVX for updates and highlights. Also look out in early 2015 for new updates to the website!

Resverlogix on the Road

We will be presenting at the Biotech Showcase 2015 / JP Morgan Annual Healthcare Conference in San Francisco, CA from January 12-14. Our presentation time is on Wednesday, January 14, 2015 at 10:00am PST on the 4th Floor, C – Mission II of the Parc 55 Wyndam Union Square.

To view other conferences that Resverlogix will be participating in, please click here.

Resverlogix in the Media

Resverlogix was mentioned in this morning’s edition of BioWorld Today, ‘Bromo’ seltzer: Merck’s Oncoethix buyout puts renewed fizz into epigenetic strategy.” Access the full story here.

Future Blog Posts

Resverlogix is committed to revitalizing our blog in 2015. We will be detailing our continued interest in epigenetics and how it can be harnessed to help patients with diabetes mellitus, Alzheimer’s disease, chronic kidney disease (CKD) and other indications. If you have a topic you would like us to blog on – please let us know!

Have a safe and happy holiday season! All the best for 2015!

With warm regards,
The Resverlogix team

Resverlogix: Our Interest in Diabetes Mellitus

Diabetes Mellitus (“DM”) is a terrible disease for which there is currently no known cure. It is the most common metabolic disease that affects humans and currently is a worldwide epidemic fueled by the wave of modernization swiping across much of the third world societies. According to previous estimates, the costs for modern societies to take care of DM ranges from 1 in every 5 healthcare dollars in the US, (American Society of Diabetes). There are two types of diabetes that affect humans, Type-1 and Type-2. The difference between these two types of diabetes is that there is a deficiency in the amount or absence of insulin otherwise it can also be described as the lack of insulin action. While Type-1 affects less people and mostly younger individuals, Type-2 most commonly accounts for roughly 90% of the cases. The cause of Type-1 Diabetes is believed to lie in defects within the immune system. In the pathogenesis of Type-2, there is direct connection between dietary habits, sedentary life styles and obesity. One of the most feared consequences of either form DM is that it is one of many major risk factors leading to the development of cardiovascular disease (CVD), the number one cause of premature death in modern societies.

Why is Resverlogix interested in the field of Diabetes Mellitus?

A major reason for our interest in DM arises from the fact that the lead compound RVX-208 in clinical trials appears to affect several parameters pointing to potential benefits in DM. The first parameter we focused on was major adverse cardiovascular events (MACE) in the DM population. In the ASSURE study, the diabetic population was a pre-specified subgroup and RVX-208 resulted in a 74% relative risk reduction in MACE. In the analysis of combined data of both the ASSURE and SUSTAIN studies, the relative risk reduction of MACE in the DM population was also 77%. An additional analysis showed that patients with DM given RVX-208 tended to have lower blood glucose vs. placebo. However, specifically in patients with DM who had low HDL, the blood glucose was significantly lower following treatment with RVX-208 vs. placebo.  It should be noted that the time required for RVX-208 to reduce blood glucose was not observed until at least 12 weeks following initiation of treatment.

The new observations above and continued analysis of our extensive database are very important for establishing the emerging role of BET inhibition in high risk vascular disease and especially in those with DM. As we continue to study RVX-208 and the collected analyzed data, we are slowly revealing further cases in which RVX-208 can excel in such areas as diabetes mellitus, chronic kidney disease, acute coronary syndrome, and other chronic diseases like Alzheimer’s disease.

The next blog with discuss Resverlogix’s current interest in Alzheimer’s disease.

Resverlogix Complies with Anti-Spam Laws

As you may have been receiving several emails from various companies, Canadian e-communication laws are changing.

Starting from July 1, 2014, we will need your permission to continue sending Resverlogix’s news, research and other correspondence via email.

What will happen?

An e-mail will be sent to you with a link that will confirm your continued interest in receiving Resverlogix emails.

What must you do?

These e-mails must be opened and confirmed, otherwise you will be automatically removed from the mailing list and no longer receive Resverlogix news email alerts.

As always, you may unsubscribe at any time in the future. The unsubscribe link is visible at the end of each electronically sent press release.

If you wish to read more on Canada’s Anti-Spam Legislation (CASL), please click here.

Thank you for your continued interest in Resverlogix.

Clinical Trials Series: The Final Steps

This is the final blog post in the clinical trial series. As discussed in the previous posts, multiple types of clinical trials exist and they generally happen in sequence, from Phase 1 though Phase 3, evaluating drug candidates’ safety and efficacy in humans which ultimately leads to accurate product positioning of the drug by Phase 3. Depending on the compound, indication(s) and trial design, completing the clinical trial process is extensive, costly and time consuming.

At the completion of each clinical trial, the principal investigators and sponsors of the clinical trial, such as biotech companies, analyze the data to determine whether the trial met the goal(s) set out for the compound. Depending on whether the compound has met the expectations of the specific primary endpoint or not, provides guidance whether the trial has succeeded based on a certain ideas of what the drug was hypothesized to do. In most trials, the investigators who design it postulate concepts prior to trial initiation a set of pre-specified endpoint(s) that they predict the compound should be able to achieve. Thus in most trials this is the so called ‘primary endpoint’ by which the trial is initially judged.

For example, if a compound is designed to lower glucose by X mg%, then results from a trial of patients given the compound should on average have glucose below X mg%. If so, then the trial is judged as being positive.  Additionally, in most trials the investigators set out multiple secondary and possibly exploratory endpoints which are used to gather further analysis and understanding of the potential of the drug. These endpoints are also important hurdles to judge activity of the compound. Based on the results of the trial, the clinical investigators decide on the next steps in the clinical development of the compound. Both primary and secondary endpoints help determine the accuracy of the investigators’ hypothesis.

Analyzing the top-line data is the first process after the completion of a trial. It determines the success of a trial. The analysis of the data to determine primary endpoint is the first priority. Ongoing analysis of data from the trial, especially that for the secondary endpoints takes time. Beyond the primary and secondary endpoints, there is very valuable information collected in the data from the trial. This is often analyzed as time permits. Continued analysis will help identify characteristics and activity of the compound not previously suspected or postulated by the investigators.

Given positive outcomes in each phase of the clinical trials process, development of the compound will continue. The goal is to work towards a Phase 3 trial that is successful and demonstrate significant improvement in treatment from existing medications. A successful Phase 3 trial will allow a company who owns the compound to file for a new drug application (NDA) with the U.S. Food & Drug Administration (FDA). If approved, they will bring the drug to market for the benefit of the entire patient population.  As the drug enters the market place, constant monitoring will take place as the drug is prescribed to patients. This is an ongoing process to collect data on the long term effects of the drug.

We hope you enjoyed reading the clinical trial series. The next post will discuss Diabetes Mellitus and Resverlogix’s interest in this wide spread disease.

Resverlogix Corp. Centralizes Head Office and Laboratory

We are pleased to announce the relocation and centralization of our main office and laboratory.

Effective May 1, 2014, our Midpark Way office and 31st Street laboratory in Calgary have relocated to:

300, 4820 Richard Road SW
Calgary, AB T3E 6L1
Tel: 403.254.9252 Fax: 403.256.8495
(Telephone and fax numbers remain unchanged)

If you have any questions, do not hesitate to contact us at info@resverlogix.com.

Best regards,
Resverlogix Senior Management