Resverlogix Launches IR App

Resverlogix has collaborated with CNW in creating an Investor Relations App for Apple and Android users!

As investors become more dependent on mobile devices for their consumption of information, they require the company’s investor relations content to be easily viewable and navigable.

This app gives Resverlogix Corp. (TSX: RVX) investors mobile access to the latest stock data, news, SEC Filings from Resverlogix Corp. It also provides proprietary company content including presentations, conference calls, videos, fact sheets, annual reports and other qualitative company information. Investors are able to receive ‘push’ notifications when new content is added to the IR App such as add events to calendars, share content and as well as download files for offline viewing.

We proudly introduce our new IR App to current and potential investors. You may check your phone’s App store and type “Resverlogix” or “Resverlogix IR App” in the search bar. It should be the first on the list!

You can also access download the Apps for your desktop and/or web browser at:

Apple Products (iPhone, iPod, and iPad) –

Android Products (Tablets and Smartphones) –

If you have any issues, please send us an email at

Understanding Our New Findings From ASSURE – hsCRP Biomarker

Yesterday Resverlogix announced new findings from continued analysis of data collected in the ASSURE trial of RVX-208 (see  One of the new findings relate to the fact that levels of a biomarker which reflect inflammation, so called high sensitivity C reactive protein (hsCRP), appears to be very useful in identifying ASSURE patients who benefited from the actions of RVX-208 to regress atherosclerotic plaque.

What does this mean in the development of RVX-208? To answer this question, important background information details the role of inflammation in the cause of atherosclerotic disease.  Inflammation of the vasculature is an integral component of atherosclerotic disease such as heart attacks, strokes and peripheral artery disease (PAD). One way to understand what is inflammation and how it becomes a part of a heart attack or other atherosclerotic vascular diseases is similar to the events surrounding an infection such as a boil on the skin. This problem begins with a skin infection and then the body reacts to it by recruiting the immune system to fight the infection. First, the infection is surrounded by the body’s immune cells so that the boil has a defined margin. Then the boil turns red, swells and becomes painful, reflecting the inflammatory response mounted by the body’s immune system to fix the problem. In a heart attack, the body is fighting off an enemy which in this case is cholesterol that collects in the arterial wall of blood vessels found in the heart. The immune system is called upon to get rid of the cholesterol particles using a pathway similar to that for fighting the skin infection. Imagine how the inflammatory response, comprised of redness and swellings were to take place in the confined space of a blood vessel within the heart. This inflammatory response may impede or completely block the flow of blood in the artery, leading to a heart attack or stroke.

To understand the idea of the inflammatory state within a given patient with vascular disease, hsCRP is a biomarker that is measured by simply sampling the blood. Patients in ASSURE were measured using this biomarker and find that those with a level > 2 mg/dL appeared to benefit markedly from the actions of RVX-208. In these patients, the actions of RVX-208 lead to a marked and significant regression in the plaque within the artery wall of blood vessels found in the heart. The amount of regression of the plaque is detailed in our recent press release. These beneficial actions of RVX-208 may arise from its direct or indirect (via increased apoA-I production and creation of functional HDL particles) effects to calm the inflammatory response.

How does this new observation help us in the continued development of RVX-208 to reduce risk in patients with CVD?  As the analysis of data from ASSURE continues, each finding should be viewed in the context of other useful observations collected in the trial.  The current finding, when added to previously announced observations, is that ASSURE patients with HDL-C below 39 mg/dL receiving rosuvastatin (5-20 mg/day) and then given RVX-208 for only 26 weeks were associated with a marked, rapid and pronounced regression of atherosclerosis coupled with reduced major adverse cardiovascular events (MACE). A recent scientific publication ( supports the idea that increased levels of hsCRP is an additional key feature of high risk CVD populations in which MACE may be reduced by further treatment. Thus the patient profile that will benefit from treatment with RVX-208, as defined previously, can now be expanded to include an hsCRP of > 2.0 mg/dL.

This information will be very valuable in designing the next clinical trial of RVX-208 in high risk vascular disease patients.

Zenith Epigenetics Launches New Website

We are excited to inform you of the new Zenith Epigenetics website You may access Zenith’s updated information on events, webcasts, news releases and financial information. This is a responsive site so it can be easily accessed on mobile devices.

Zenith Epigenetics Corp. is a science driven organization with a unique drug discovery platform in the area of epigenetics. Focusing on the inhibition of BET bromodomains, Zenith has successfully identified novel compounds for diseases in the areas of oncology and autoimmune disease. Zenith’s strong organization allows it to efficiently and rapidly to explore and progress these molecules from discovery to pre-clinical development, and through partnerships building a pipeline of products for both niche opportunities as well as more common diseases.

Questions or comments on Zenith can now be sent to

Thank you for visiting Zenith’s new site.

Eligibility for Investment of Zenith Shares

The company has received several inquiries about whether shares of Zenith Epigenetics Corp. (“Zenith”) are qualified investments for registered investment plans even though they are not listed for trading on a stock exchange.

On June 3, 2013, Resverlogix Corp. successfully spun out RVX Therapeutics Inc. into a newly incorporated company, Zenith Epigenetics Corp. (“Zenith”). This was completed by a Plan of Arrangement pursuant to the Business Corporations Act (Alberta). Shareholders of Resverlogix therefore received one share in Zenith for every share held in Resverlogix prior to the agreement at the effective date.

Shares of Zenith should be “qualified investments” for the purposes of the various registered investment plans provided for in the Income Tax Act provided Zenith is a “public corporation” as defined in the Act.

In particular, regulation 4900(1) (b) of the Income Tax Regulations provides that for the purposes of the various definitions of “qualified investment” in the sections relating to RRSPs (Registered retirement savings plans), DPSPs (Deferred profit sharing plans), RRIFs (Registered retirement income plans), RESPs (Registered education savings plan), RDSPs (Registered disability savings plans), and TFSAs (Tax-free savings accounts), a share of a public corporation (other than a mortgage investment corporation) is a qualified investment.

Notwithstanding that the shares of a corporation may not be listed on a designated stock exchange in Canada, the corporation may still be a public corporation if it so elects. Paragraph (b) of the definition of “public corporation” in subsection 89(1) provides that a corporation that complies with prescribed conditions relating to share ownership and trading, and that makes the required election, is a public corporation as of the time the election is made. Furthermore, the postamble to that definition provides that where a corporation has, during its first taxation year, become a public corporation (such as by making the election described above), it may elect in its income tax return to be deemed to have been a public corporation from the beginning of the year.

Zenith shares meet the prescribed conditions and have made the first election and will make the second election in prescribed manner and on a timely basis, consequently it is a public corporation, and the shares thereof qualified investments from the time they were issued under the plan of arrangement.

Clinical Trials Series: The next steps

Most clinical trials are conducted to test a medical compound, a device or a diagnostic test in human volunteers and/or patients to add evidence and medical knowledge regarding the treatment of diseases.  This information involves both efficacy and safety of a new treatment.

Before a clinical trial can start, a detailed protocol must be developed. A clinical trial protocol determines why and how a clinical study is conducted. This protocol is usually designed by experts and investigators from the company (sponsor) and/ or organizations interested in conducting the clinical trial. The clinical trial needs to be approved by internal review boards at trial sites and by the federal health authorities such as the FDA or Health Canada.  The protocol will include the reason behind the study, what will be tested, procedures of testing, participants’ eligibility criteria, number of participants, and length of study. Inclusion criteria are the factors that determine subjects’ eligibility for the trials. Exclusion criteria determine which subjects are disqualified from participating. Inclusion and exclusion criteria may include age, gender, type of disease, disease stage, current medical treatment and medical history.

As sites become active and approvals are received, patients begin enrolling. The speed at which patients are enrolled in any clinical study depends on a myriad of factors. The most important factor in enrollment is, of course, inclusion and exclusion criteria. If the disease being studied is rare or if there is strict inclusion and many exclusion criteria, then enrollment can be slower, as compared to a trial for a common disease with few exclusion criteria.

Clinical trials may be funded by healthcare companies, including biotechnology and/or pharmaceutical companies, academic and medical centers, government agencies and other organizations. All entities interested in conducting clinical trials would determine the budget necessary for each trial and raise the necessary capital for the study.

Clinical studies may be conducted at multiple sites including hospitals, universities, and community clinics. It is not uncommon for large clinical outcomes trials to enlist several hundred trial sites in multiple countries. The location is usually determined by who is conducting the study and the availability of the patient population.  Clinical studies are led by a principal investigator (PI), who is often a medical doctor, and she/he is supported by a group of doctors, nurses, social workers, and other healthcare professionals. The duration of the clinical study varies from trial to trial, depending on the phase of the trial and what is being investigated.

The next blog will discuss the final steps in the clinical trials series.

Timeline and Procedures Regarding Release of Data from Resverlogix’s ASSURE Trial

At this time no individual, institution or organization has any knowledge of the final data set for the ASSURE clinical trial. Once final data has been tabulated in late June, the data will then be shared for the first time with Resverlogix, Dr. Steve Nissen, Dr. Steven Nicholls and other Clinical Steering Committee members.

The Resverlogix management team will then share the data with Resverlogix’s Board of Directors in order to properly execute Resverlogix’s strategic planning going forward. The data for the primary endpoint, meaning the plaque regression calculations, will be promptly announced via news release and accompanied by a conference call. The data in this trial should determine if we have achieved plaque regression. Other available data, such as secondary endpoints and safety aspects will also be commented on in the news release.

Some secondary endpoint data, such as Apo AI levels, may not be ready at the time of the news release announcing the primary endpoint data. This data may be presented at a later time along with the full topline tables and data at a global cardiovascular event such as the European Society of Cardiology (ESC) Congress 2013 in Amsterdam in August/September.

In order to participate in prestigious congresses such as the ESC, AHA and ACC, the data being presented must be of original release. Our goal is to satisfy embargo regulations while providing Resverlogix stakeholders with key results in a timely fashion. Any negative data would not be deferred and would be released as soon as they have been analysed and available.

The ASSURE trial data is pivotal not only to Resverlogix but also for patients, so we will continue to develop our timelines and procedures to determine the most efficient way to advance RVX-208 to the market.

Clinical Trials Blog Series: Commencement of a trial

The practice of modern medicine is based on studies that provide evidence to support whether an approach for treating a disease is beneficial or not. Measuring the effectiveness of a particular treatment is done by conducting clinical trials. In this series of blogs, we will discuss how clinical trials help us determine whether a treatment for a particular disease is safe and effective.

Any scientific experiment, including human clinical trials, begins with a hypothesis. The trial is then conducted to test the hypothesis. For instance, it is a hypothesis that drug X is safe and effective for treating disease Y.

Clinical trials are normally divided into 4 different phases. Phase 1 is usually tested “First-In-Man” and involves single dose administration to healthy subjects. Many doses are tested to find the maximum tolerated dose. When a few doses have been selected, testing will occur in patients. This is called Phase 2 and involves normally 3 or 4 different doses given over a period of 2-3 months. It is not unusual that additional fine-tuning of doses are tested in larger patient samples to clearly confirm one efficacious and safe dose, which is called a Phase 2b. Finally, in order to file a registration (NDA), one or two larger Phase 3 studies need to be accomplished in large patient samples where you aim to seek your indication, i.e.) to prevent events of cardiovascular disease. Those studies can involve more than 10,000 patients. When a drug is tested after registration within the same indication or in a new dose, it is called Phase 4. Usually, testing a hypothesis in clinical studies requires comparing results in patients given the drug to the results in patients who were not. This is called placebo-controlled.

The results of most clinical trials are measured by something called endpoints. The endpoints determine whether the initial hypothesis is correct or not. Once the endpoints are determined, the next step is to define a target patient population for testing the hypothesis. The patient population is usually made up of people who are suffering whatever condition the drug is intended to treat. A list of criteria are created to define this population called “inclusion criteria.” A list of criteria that would exclude a subject from the study is also created called the “exclusion criteria.” The patients that fit the inclusion criteria but not the exclusion criteria are allowed to enroll in the study.

Very often, studies are also “randomized”. Patients who meet the inclusion criteria and enroll in a clinical study will receive either the drug being tested or the placebo. This assignment to either drug or placebo is done randomly – like the flip of a coin. This is to ensure there is no bias in choosing the patients in each group. Another important way to limit any potential bias in a clinical study is to make them “blind.” Blinding means that nobody involved in the study knows whether a patient is receiving the drug or the placebo.

Our next blog will discuss trial design, protocol, site openings and commencement of dosing.


Learning how RVX-208 inhibits BET proteins has been significant in building Resverlogix’s drug pipeline.

Our lead drug candidate, RVX-208 binds to a region of the BET proteins called a bromodomain that leads to the increase in ApoA-I. These bromodomains are found not just in BET proteins, but also in more than 50 other proteins, a relationship known as a “superfamily”.

While this is a rapidly developing field of research, it is already clear that bromodomain superfamily members control the expression of key genes underlying cancer, inflammation, disorders of the central nervous system and metabolic diseases. The ability of new compounds to inhibit the actions of superfamily members has the potential to become a treatment for these diseases. Most of our work has focused on a small subset of this superfamily, the BET proteins, whose bromodomains specifically bind to RVX-208.

In preclinical laboratory testing, we have observed that, in addition to its ability to raise ApoA-I, RVX-208 may also have anti-inflammatory properties. This may contribute to the recent observation that RVX-208 can significantly lower a biomarker of inflammation called CRP (C-reactive protein) in the clinic. We used this as a starting point to discover compounds related to RVX-208 that had more potent actions as anti-inflammatory agents. Some of these molecules have shown efficacy in animal models of autoimmune disease, including arthritis and multiple sclerosis and we are currently discovering additional compounds with structures very different to RVX-208 to develop as an oral therapy for these diseases.

Recently, based on new evidence that BET proteins are involved in cancer, we have begun exploring the actions of our new compounds in this disease. Studies with some of these compounds in a mouse cancer model have shown marked inhibition of tumor growth vs. placebo.

In summary, the understanding of how RVX-208 inhibits BET proteins has led us to many new areas of research and the ability to explore treatments for many disease states. Please visit the Programs section of our website for more information.

Readers, writers & erasers- what exactly does this mean in epigenetics?

The preceding blog dealt with the partnership between histones and DNA that allows the two entities to form chromatin. This compact structure can fit into the restricted confines of the nucleus inside a cell. When the chromatin is in a compact or closed state the genetic information encoded within the DNA is dormant. To access the genetic information encoded in the DNA, the chromatin must become more open requiring the dissolution of the partnership between DNA and the histones. This epigenetics image will still be helpful when reading this blog.

One of the most important epigenetic processes is to strengthen or weaken the interactions between histones and DNA. When the interaction is strong the histones are bound tightly to the DNA this means the chromatin is in a closed or dormant state. In order to access the genetic information in chromatin, it has to become more open.

In transitioning from closed chromatin to a more open conformation, the interactions between the histones and DNA must be dissolved. This process requires epigenetic “writer” proteins to alter histones by adding an acetyl group. This modification blocks the ability of the histone to bind DNA and thus making the chromatin more open.

In contrast, epigenetic “eraser” proteins remove the acetyl group from the histones restoring the interaction between the histone and DNA, leaving the DNA once again in a closed conformation.

While “writers” and “erasers” have opposite effects on histones, the epigenetic “readers” are proteins that do not alter the histone but rather detect the acetyl group within the histones. BET proteins are “readers” and they are the target that binds RVX-208.

The actions of the “readers” are important to the mechanism-of-action (MoA) of RVX-208 because our lead compound looks and behaves like an acetyl group on histones. So picture a situation where the ApoA-I gene becomes more active. The first step to increase activity of the gene requires the histones to relinquish their hold on ApoA-I DNA allowing it to take a more open conformation. This process involves the acetylation of the histones bound to the ApoA-I gene. The presence of the acetyl group attracts “readers” such as BET-proteins. RVX-208 interrupts the interaction of the BET-protein with the acetyl group in the histones triggering a cascade of events that enhances ApoA-I gene activity and ultimately leading to production of more ApoA-I protein.

Here is a link to an animation explaining how RVX-208 affects epigenetic processes in activating the ApoA-I gene:

BET-proteins belong to a large family of proteins that have common features in structure and activity. Learning how RVX-208 affects the activity of the ApoA-I gene has given us a deep understanding of epigenetic mechanisms. This knowledge gives us the tools to explore treatments for diseases in many therapeutic areas.

The exciting new frontier of epigenetics

Last year we announced the mechanism-of-action (MoA) by which RVX-208 increases ApoA-I production. Specifically that RVX-208 is an inhibitor of the Bromodomain and Extraterminal Domain (BET) proteins. RVX-208 acts on BET proteins, including BRD4, a member of the BET-protein family, leading to increased transcription of the ApoA-I gene followed by production of more ApoA-I protein.

What exactly does this mean? The next few blogs will be devoted to this question. In this blog we will start a two part series on Epigenetics 101, to be followed by a deeper dive into the actions of RVX-208 involving epigenetic processes. The knowledge gained from our studies of RVX-208 laid the foundation for our epigenetics platform.

Whether a gene is asleep or awake, in other words dormant or active is depicted in the figure below. On the left there is a chromosome which is comprised of double stranded DNA together with proteins. These two components act in partnership to form a compact structure that fits into the nucleus of a cell.

This partnership between DNA and proteins is not only responsible for chromosome structure it can regulate its activity. The DNA contains genetic information encoded in the sequence of four nucleotide bases. Although DNA contains all this genetic information, by itself it’s useless. Think of DNA like a computer hard drive and in order to extract the information from it, software is needed. The proteins binding to and interacting with the DNA act as the software.

As shown in the left side of figure below, for the DNA to be in ‘tightly wound up’, inactive or in a ‘closed’ state, it binds to a set of proteins called histones. When the DNA is in the ‘closed’ state, the genetic information it contains is stored and not actively used.

For the DNA to become active and its genetic code available to be read, it must be converted to an ‘open’ conformation. For example, in order for the ApoA-I gene to be active and leading to the production of more ApoA-I protein it must be in an open conformation. As the DNA transitions from the closed to the open conformation, it does so by dissolving the partnership with the histones. When the histones leave, other proteins are able to come in and start acting as the software to interpret the genetic information encoded in the DNA. This is how epigenetics controls the activity of certain genes.

In the next blog, the topic of epigenetic readers, writers and erasers will be explained and how the actions of these proteins that are involved in epigenetics help us understand how RVX-208 works.