New CEO Video Presentation

On March 23, 2016, Resverlogix’s President and Chief Executive Officer Donald McCaffrey had the opportunity to present at the Richmond Club in Toronto, ON. Please access the video presentation here: http://www.richmondclub.com/resverlogix-presentation-march-23-2016

More information about the Richmond Club can be found at: http://www.richmondclub.com/

Sanofi Biogenius Competition CTV News feature

Resverlogix is committed to community investment. As a scientific leader in our field, we believe it is important to support innovative, educational programs for our youth in real-world settings. We recognize that providing an enriched learning environment for today’s youth will help to cultivate our scientific leaders of tomorrow. Resverlogix is pleased to open our state-of-the-art lab to students with scientific aspirations.

For the past 25 years, Sanofi Biogenius Canada (SBC) has helped over 4,000 high-school student pursue ground-breaking scientific research projects, which have helped to pave future studies and successful careers in biotechnology.  Resverlogix is pleased to work with MindFuel, the regional coordinator of SBC in supporting this program. Resverlogix has mentored a student in its Calgary lab for the past several months in conducting research, compiling results, and preparing a scientific poster to present to a panel of judges at the regional competition. The winner of this competition will advance to the national competition at the National Research Council in Ottawa and finalists will move on to the international competition at the BIO International Convention.

CTV news filmed on location at Resverlogix’s lab, airing a segment on March 29th, “Kids bring their science research to real labs for competition.” Please access the links to the news broadcast here:

http://calgary.ctvnews.ca/mobile/kids-bring-their-science-research-to-real-labs-for-competition-1.2837044

http://calgary.ctvnews.ca/kids-bring-their-science-research-to-real-labs-for-competition-1.2837044

Pharmacoeconomics

With the aging population and increased prevalence of chronic diseases, such as cardiovascular disease (CVD), there is a greater need for effective and innovative pharmaceutical interventions to address this trend. In concert with the novel drug development, there is a growing awareness of and focus on the “value proposition” of these new interventions and their potential impact on healthcare resources, especially when drug budgets are becoming more and more constrained around the world. Developed countries must allocate a significant amount of their GDP to healthcare expenditure in order to provide a high standard of care for their residents. According to the World Bank, Canada and the United States allocated 10.9% and 17.1% of their GDP on healthcare expenditure in 2013, respectively. With increasingly limited resources, the growing cost of drug development, and other economic constraints, drug developers must now demonstrate more value for pharmaceutical costs.

Pharmacoeconomics represents one aspect of health economics which focuses on valuating a pharmaceutical intervention by using both analytical and descriptive techniques that consider both the cost, and the potential outcomes that result from such an intervention (overall value). It is not focused on the reduction of pharmaceutical costs but rather it is used to determine whether or not an intervention offers strong value for the costs it incurs. Pharmacoeconomics is principally used by authorities as a decision-making resource in the adoption of a new intervention, in setting drug prices and in development of clinical practice guidelines. Two simple examples of the types of analyses used in pharmacoeconomics are the incremental cost-effectiveness ratio (ICER), and number needed to treat (NNT).

Incremental Cost-Effectiveness Ratio (ICER)
ICER is a statistical tool that allows for the comparison of one therapeutic intervention to another (i.e. a newly developed intervention compared to an existing treatment or standard of care treatment for a specific disease). ICER is one of many tools that serve as potential benchmark for the basis of cost-effectiveness analysis. It is calculated by taking the difference in cost of the two interventions, novel treatments versus standard of care, divided by the difference in their effectiveness. The costs tend to be monetary values such as how much money had to be spent in order to improve a measureable outcome such as a death, heart attack or stroke in CVD patients.

Number Needed to Treat (NNT)
NNT is another treatment-specific measure of the effectiveness of an intervention or therapy in achieving a desired outcome. The NNT is an epidemiological measure representing the average number of patients that need to be treated over a one year period to prevent one additional adverse outcome (such as death, myocardial infarction, or stroke in the case of CVD). In simple terms, a lower NNT demonstrates that an intervention is providing stronger value over standard of care treatment. For example, if a novel intervention illustrates an NNT of fifty, this implies that fifty patients have to be treated with the intervention for one year to prevent one outcome.

This introduction to some of the concepts and tools used in pharmacoeconomics highlights the importance, utility, and benefits of this field during drug development. Not only must a new intervention demonstrate strong efficacy, but due to economic constraints affecting health systems worldwide, it must answer the question, “does this novel intervention provide additional value for the cost compared to other interventions that are readily available?” Pharmacoeconomics plays a critical role in the overall value proposition of any new potential intervention that is planning to enter into the market and will determine whether or not an intervention is adopted by physicians and pharmacists and reimbursed by third party payers (government and insurance companies). It is a growing field that assists with economic decision making, and ultimately leads to more cost-effective and evidence-based pharmaceutical development.

2016 Outlook: A video message from President & CEO Donald McCaffrey

President & CEO Donald McCaffrey was interviewed by Executive Video at the J.P. Morgan 34th Annual Healthcare Conference (January 2016, San Francisco, CA). Please access the video here: Resverlogix: 2016 Outlook

Current Treatments for Complement Mediated Diseases

Over the past few months, we have detailed a blog series on the Complement System. Recent posts highlighted ‘What is the Complement System?’ and ‘Complement Mediated Diseases.’ The focus on today’s blog is: Current Treatments for Complement-Mediated Diseases.

Pathological activation of the complement cascade underlies multiple human diseases. Thus, development of treatments that can modulate inappropriate complement activation is of great clinical interest. Currently, several complement inhibitors are in pre-clinical and clinical development and one has been approved for treatment of complement-mediated diseases.

Eculizumab, developed and marketed as Soliris® by Alexion Pharmaceuticals, was the first and currently the only approved drug for treating PNH and aHUS, and its therapeutic potential is currently being explored in additional complement-mediated diseases. It is a first in class, recombinant, humanized monoclonal antibody that selectively interacts with complement C5, preventing its cleavage into C5a and C5b. C5b is an essential component of the membrane attack complex called MAC, which leads to cell disruption when complement is activated. Thus, preventing formation of C5b precludes the formation of MAC and subsequent cell destruction. In 2007, the FDA approved Soliris® for all patients with PNH and, more recently in 2011, Soliris® gained FDA approval for all patients with aHUS. Soliris® treatment requires patients to visit a physician every two weeks to receive drug administration via IV infusion over 35 minutes for adults and 1 to 4 hours for children (per the label). Currently, Soliris® is considered to be one of the most expensive drugs in the world with annual costs of treatment over $500,000 USD. Eculizumab is currently being investigated in clinical trials for several complement-mediated conditions and diseases including prevention of thrombosis after renal transplantation, treatment of antibody-mediated rejection following renal transplantation, treatment of patients with refractory generalized myasthenia gravis (gMG), and treatment of patients with relapsing neuromyelitis (NMO). While Soliris® is considered to be an innovative treatment for PNH and complement-mediated diseases, several unmet needs exists in this therapeutic field including improved efficacy in suboptimal responders (such as the PNH patients who experience residual anemia and require continued blood transfusions following administration of Soliris®), route of administration, susceptibility to infection, and dosing frequency. As such, more infrequent dosing and self-administering of doses represent important focuses for new treatments targeting complement-mediated diseases.

Complement C5 plays a central role in complement activation which makes it an effective therapeutic target to reduce complement activity and ultimately prevent cell lysis. However, although inhibition of C5 blocks cascade activation downstream of C5, it does not prevent activation of upstream components of the pathway. For example, even in the presence of eculizumab, C3, a complement component upstream of C5, is cleaved into C3a and C3b fragments. Then, C3b accumulates on the surface of red blood cells making them susceptible to extravascular hemolysis, which is the most common cause of residual anemia in eculizumab-treated patients.

Most of the therapeutic agents (currently available or in development) target either C5 or C3. Additional complement factors that inhibit cleavage of C3 into C3a and C3b, such as factor D and factor B, are also being investigated as potential targets to reduce aberrant complement activity. In October 2015, a Nature Reviews Drug Discovery review highlighted the drugs currently in development targeting the complement system (Morgan and Harris. 2015. Nature Reviews Drug Discover 14, 857-877). The remainder of this blog post will detail some of these drugs and their therapeutic targets.

C5-Directed Therapeutics in Development

  • ALN-CC5 is an RNAi-based (RNA interference) treatment currently being developed for complement-mediated diseases by Alnylam Pharmaceuticals that targets C5. ALN-CC5 is a small interfering RNA (siRNA) that acts specifically in the liver (the main production site for most complement proteins) via a targeted mechanism and binds the single stranded mRNA of C5. The resulting double stranded RNA is targeted for degradation, thus reducing C5 mRNA levels and ultimately C5 protein production.
  • Ophthotech has developed an aptamer (chemically synthesized single-stranded DNA or RNA molecule that binds to a select target with high affinity and specificity) that inhibits C5 and is currently under investigation in phase II studies.
  • ALXN1210 and ALXN5500 are C5 targeted therapeutics currently being clinically investigated by Alexion Pharmaceuticals. ALXN1210 is an anti-C5 monoclonal antibody while ALXN5500 is also a C5 inhibitor; however the mechanism and dosing have yet to be disclosed.
  • Novartis has also developed a C5-specific monoclonal antibody, LFG316, which is currently in phase II.
  • Akari Therapeutics recently completed phase I studies with their lead therapeutic Coversin. It is a recombinant small protein derived from a native protein, discovered in a specific species of tick, which functions in modulating the immune system of the host such that the tick can feed without triggering an immune response. The compound is known to target C5 and is self-administered by subcutaneous injection.
  • RA101348 is a peptide inhibitor of C5 under development by Ra Pharmaceuticals. It is currently in pre-clinical development but has been shown to bind the C5 protein with high affinity. The company hopes to launch first-in-man studies by the end of 2015.

C3-Directed and Additional Complement Targeted Therapeutics in Development

  • Compstatin, a small molecule inhibitor of both C3 and the active C3b fragment, has been shown to be effective in preventing complement activation in preclinical models. There are multiple compstatin analogs currently in development by Apellis and Amyndas Pharmaceuticals, including APL-2 and AMY-101. The phase I safety trial for APL-2 is currently recruiting patients while phase I studies with AMY-101 were expected to begin in 2015.
  • C3 convertase (which cleaves C3 into C3a and C3b) functions by activating and amplifying the three complement pathways. It has two forms, one from the classical and lectin pathways and the other from the alternative pathway. Factor H is a complement inhibitor that modulates the activity of C3 convertase from the alternative pathway. AMY-201 or mini-FH improves the binding affinity of factor H to specific C3 fragments and has illustrated strong preclinical results.
  • Complement factor D functions by cleaving complement factor B bound to C3b, resulting in the formation of the alternative pathway C3 convertase mentioned above. Achillion Pharmaceuticals is currently developing compounds preclinically that target and inhibit factor D to prevent the formation of C3 convertase. These compounds have illustrated strong preclinical data in vitro and in primates.
  • Properdin and complement factor B function in a similar manner to complement factor D in that they activate the alternate complement pathway. NovelMed is currently preclinically developing an anti-properdin antibody (NM9401) while Novartis and Alexion both have preclinical programs focused on complement factor B inhibitor programs.
  • Omeros Corporation has a mannan-binding lectin associated serine protease (MASP) inhibitor program with two compounds in development. OMS721 targets MASP-2 and is currently in a phase 2 clinical trial for the treatment of aHUS. OMS905 is an inhibitor of MASP-3 which is undergoing preclinical studies for PNH. The MASP proteins are primarily involved in the activation of the lectin pathway.
  • True North Therapeutics is currently developing antibodies; TNT009 and TNT010 that target classical complement pathway enzymes including C1s (which functions in the formation of classical pathway C3 convertase). TNT009 recently completed phase Ib studies while TNTN010 is in the preclinical stages of development.

Resverlogix’s Approach

Resverlogix is taking advantage of the transcriptional mechanism of RVX-208 to modulate the expression of multiple complement genes including some of those identified as potential therapeutic targets in this blog, with the ultimate objective to decrease the pathological activation of the complement system. As per the press release on September 24th, 2015, Resverlogix is currently engaged in designing a pilot proof-of-concept trial in complement mediated diseases, with the first clinical trial in Paroxysmal Nocturnal Hemoglobinuria (PNH).

This is the final entry for the Complement System blog series. At this time, Resverlogix would like to take this opportunity to wish you a very happy and safe holiday season! We look forward to kicking off the New Year at the Biotech Showcase and JP Morgan conferences in San Francisco. Thank you for your continued support!

With warm regards,

Your RVX Team

 

World Diabetes Day

On the 14th of November every year, the International Diabetes Federation (IDF) celebrates World Diabetes Day (WDD). WDD is a worldwide campaign established in 1991 by the IDF and the World Health Organization. The campaign was developed to engage the IDF and its members to raise awareness about the growing economic and healthcare burden that diabetes represents. This year’s WDD campaign focused on establishing and strengthening public health education and to encourage lifestyle changes to prevent Type-2 diabetes. In 2015, the IDF distributed its “Framework for Action on Sugar”. This initiative targeted policies to reduce the consumption of sugar and aid in the production and availability of healthier foods. Excess sugar consumption is one of the most important contributors to the risk of developing Type-2 diabetes.

In conjunction with the WDD and the upcoming World Diabetes Congress in Vancouver on December 1st, the IDF released new epidemiological estimates for the prevalence and growth of diabetes worldwide. In 2015, it is estimated that 415 million people worldwide have one type of diabetes and this number is expected to increase to 642 million people worldwide by 2040 (IDF Diabetes Atlas 2015). Based on these staggering numbers, an estimated one in 11 adults have diabetes worldwide (IDF Diabetes Atlas 2015).  Regional estimates suggest that the Western Pacific region has the highest number of individuals with diabetes, 153 million, however North America has the highest prevalence per capita with one in 8 adults suffering from the disease (IDF Diabetes Atlas 2015). On a per country basis, China has the largest diabetic population and the second highest diabetes-related health care expenditure (IDF Diabetes Atlas 2015).

One of the most severe consequences of diabetes is that it is a major risk factor for the development of cardiovascular disease (CVD). Diabetes and its associated complications, such as CVD, are leading causes of death in most countries. In some modernized and developed countries, CVD is responsible for 50% of deaths due to diabetes (IDF Diabetes Atlas 2015). According to the IDF, an estimated 5 million adults died from diabetes in 2015, which is equivalent to an astonishing one death every six seconds. From 2011 through 2013, the estimates of mortality due to diabetes increased by 11% which is in contrast to all other non-communicable diseases worldwide which illustrated declining mortality rates (IDF Atlas 2015). The mortality of diabetes reflects a larger burden compared to other high profile public health concerns such HIV/AIDS, tuberculosis and malaria.

In the recently commenced phase 3 BETonMACE clinical trial, Resverlogix is exploring the potential benefit of apabetalone (RVX-208) on the reduction of major adverse cardiac events (MACE) in patients with type 2 diabetes mellitus. This study and ongoing laboratory research will aid in establishing the emerging role of BET inhibition in high-risk vascular disease and especially in those with diabetes.

The Complement System: Part 2

Complement Mediated Diseases

As discussed in part 1 of this blog series, the complement system is a network of tightly regulated proteins which are a key part of the innate immune response. The complement system is initiated by the identification of a pathogen or antibody by complement proteins which trigger a cascade that results in cleavage of inactive proteins by a series of proteases, culminating in inflammation, phagocytosis and the assembly of the membrane attack complex (MAC). This protein complex assembles on the surface of target cells, creating a pore that results in the lysis or bursting of the specific cell. When activated, the complement system promotes inflammatory response and mediates lysis and clearance of microbial invaders or diseased host cells. Because of its central role in immune response, complement is a target for immune evasion and a contributor to many disease states. Several mechanisms regulate complement activation and deactivation. In a pathological state, inappropriate initiation of the complement cascade or deficiencies in specific factors or regulators can result in aberrant activation leading to host tissue damage. This blog will explore two diseases that develop as a result of abnormal activity of the complement system: paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic-uremic syndrome (aHUS).

PNH is an acquired rare disease that occurs as a result of a mutation in hematopoietic stem cells (cells that give rise to blood cells). The disease manifests itself in the complement-mediated destruction of red blood cells (RBCs), a process known as hemolysis with potentially fatal consequences. In healthy individuals, RBCs and other blood cell types have specific cell surface proteins that function to inhibit the complement system and ultimately protect cells against formation of the MAC. The root cause of this disorder lies in specific protein anchors, which act as tethers for proteins responsible for protecting blood cells from the activity of the complement system. CD59 and complement decay-accelerating factor (DAF) function as such inhibitors by impeding the activity of the enzymes that activate C3 and C5, respectively. These regulators are membrane-bound via a glycophosphatidyinositol (GPI) anchor. Due to the acquired mutation in their hematopoietic stem cells, patients with PNH do not express these host proteins and their RBCs become subject to complement-mediated destruction. A direct link exists between excessive complement activation and the clinical manifestation of PNH. The resultant excessive RBC lysis causes transfusion dependence in these patients. Symptoms of PNH include extreme fatigue, abdominal pain, anemia and hemoglobinuria (the release of free hemoglobin into the urine), which can lead to renal failure.

A life threatening complication of PNH is repeated thrombosis (blood clot formation) which is the leading cause of death in PNH, accounting for at least 40% of PNH mortality. PNH has an estimated annual incidence rate of 1-5 cases per million in the general population. A UK study found that approximately one-third of patients diagnosed with PNH died within 5 years of diagnosis despite receiving the current standard of care. Historically, the median survival has been 10 to 15 years from the time of diagnosis.

aHUS is a severe kidney disease associated with genetic alterations of complement components, modulators and inhibitors that result in excessive activation of the complement cascade. Genetic defects cause excessive cleavage and activation of complement components. Regulatory proteins such as factor H, factor B, membrane cofactor protein (MCP), factor I or thrombomodulin as well as the enzymes that activate C3 and C3 itself have all been implicated in the manifestation of aHUS. The identified genetic defects incur an amplified generation of C3 and C5, main components in the cascade, resulting in increased MAC formation at the endothelial cell surface. This results in damage to cells that line blood vessel walls, resulting in exposure of the underlying matrix and thrombus formation. Abnormal blood clot formation in the small blood vessels in the kidneys eventually leads to kidney failure. A direct link exists between excessive complement activation and the clinical manifestation of aHUS.

The estimated annual incidence rate for aHUS is 2 cases per million in the general population. Genetic mutations in at least 10 different complement regulatory genes and complement components have been identified in aHUS patients; however mutations are not identified in 30-50% of diagnosed patients. Children and adults alike are susceptible to developing the disease. During the first year after diagnosis, outcomes include permanent kidney damage requiring dialysis or death despite currently available transfusion therapies.

Despite current therapies for the treatment of both PNH and aHUS, a significant unmet need remains. Given the organization of the complement system, there are multiple points for therapeutic intervention which would attenuate the activity of this system in diseases where over activation is the driver of the pathology. Our final blog to this series will address Current Treatments for Complement-Mediated Diseases.

 

 

The Complement System: Part 1

On September 24, 2015, Resverlogix announced the commencement of an orphan disease program specific for complement-mediated diseases. Apabetalone (RVX-208) has been shown to modulate the complement pathway, which has known roles in cardiovascular disease and a variety of orphan indications. Based on these findings, Resverlogix plans to pursue proof-of-concept trials in complement mediated diseases, with the first clinical trial targeting Paroxysmal Nocturnal Hemoglobinuria (PNH).

Over the next few weeks, we will be detailing a series of blog posts highlighting the complement system, complement-mediated diseases and current therapeutic treatments for patients suffering from such diseases. The series will include three blog posts:

  • What is the complement system?
  • Complement-mediated diseases (examples include atypical hemolytic-uremic syndrome (aHUS) and PNH)
  • Current treatment for complement-mediated disease

What is the Complement System?

The immune system is made up of special cells, proteins, tissues and organs, which work in concert to defend the human body against germs and microorganisms. It is the body’s defense against foreign pathogens (biological entity that causes disease or illness) as well as abnormal cells that are derived from host tissues. This system is composed of two main parts, the innate immune response and the adaptive immune response. Several molecular components, such as complement proteins, cytokines and acute phase proteins, act in both the innate and adaptive immune responses.

The complement system represents one of the major effector mechanisms of the innate immune response, and comprises more than 30 blood soluble or membrane-associated proteins, the majority of which are synthesized by the liver. Most complement proteins circulate as pro-proteins (inactive until acted upon by specific enzymes) and the complement system remains inactive until triggered. Recognition of an antigen on the surface of a pathogen or a diseased cell activates the cascade that allows for conversion of complement pro-proteins into active components. The end-result of this activation is in the massive amplification of the response and in the generation of the membrane attack complex (MAC) on cell surfaces. The MAC forms a pore that spans the membrane of the target cell, resulting in cell lysis. Specific complement protein cleavage products generated during cascade amplification can also act as inflammatory mediators (C3a and C5a) or recognition molecules that allow for clearance of damaged cells (C3b and C4b) (see figure).

Complement

 

In general, the activation of the complement cascade results in the enhanced clearance of antigens (phagocytosis), the enhanced recruitment of macrophages and neutrophils into the area (inflammation), the cell lysis of foreign and abnormal cells and the enhanced agglutination or the clustering and binding of pathogens. Complement activation occurs through three principal pathways: classical, alternative and lectin (see figure). Though various factors can initiate complement activation (including MBL, C1q, C3), all three main pathways converge at the cleavage of C3, the most abundant complement protein in blood. Several mechanisms regulate complement activity including enzymes such as plasma carboxypeptidases and proteases.

Excessive complement activity is associated with several inflammatory, autoimmune, neurodegenerative and infectious diseases. The involvement of complement in the pathology of such diseases may be a result of either inappropriate initiation of the complement cascade or deficiencies in specific factors or regulators of the various pathways resulting in aberrant activation. Examples of such diseases include PNH and aHUS.  Current therapies for complement disorders do not adequately treat the disorder are prohibitively costly.  Combined, there is significant unmet need for individuals and families that are coping with the challenges of these disorders. Our next blog post will discuss complement-mediated diseases in more detail.

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: https://www.youtube.com/watch?v=Xwd6fT8xFJw Resverlogix also webcast from Rodman & Renshaw. The archived presentation can be accessed here:  http://wsw.com/webcast/rrshq25/rvx/

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 www.resverlogix.com. We can also be followed on Twitter @Resverlogix_RVX https://twitter.com/resverlogix_rvx.