Resverlogix’s 2017 Outlook

Resverlogix’s President and CEO Mr. Donald McCaffrey had the opportunity to sit down with Executive Video at the 2017 J.P. Morgan Healthcare Conference in San Francisco, CA on January 11th, 2017 and provide a Corporate Outlook for 2017. The video can be accessed here:

ESC Congress 2016 Epigenetics Symposium: Meeting Highlights, Videos & Slides


Resverlogix supported a PACE-CME educational symposium on Epigenetics at the European Society of Cardiology (ESC) Congress 2016, titled: “A Novel Approach for High CV Risk Patients with Diabetes: The Potential of Epigenetics,” featuring Key Opinion Leaders in cardiovascular disease and diabetes.

Featured presenters included:

Prof. Kausik Ray, Imperial College, London, UK: The high risk diabetes patient with cardiovascular disease: What else can we target to reduce cardiovascular risk?

Dr. Jorge Plutzky, Brigham and Woman’s Hospital, Harvard Medical School, Boston, MA: Understanding BET inhibition as a novel pathway for cardiovascular risk modulation. 

Prof. John Kastelein, Academic Medical Center, Amsterdam, Netherlands: BET inhibition in cardiovascular disease: A new dawn?

Meeting Highlights, Videos and Slides from the symposium can be accessed HERE.

Resverlogix’s Poster Presentation and eVideo from the EASD

On September 14, 2016, Dr. Norman Wong, Chief Scientific Officer of Resverlogix Corp. presented an abstract entitled “Apabetalone (RVX-208) acts on epigenetics to lower Major Adverse Cardiovascular Events (MACE) in diabetes patients with atherosclerosis via microbiome activity” at the prestigious annual meeting of the 52nd EASD Annual Meeting in Munich, Germany. The poster was presented in an oral presentation and an ePoster video session based on the latest data summarizing the benefits of apabetalone in an in vitro model that reflects patients with diabetes mellitus (DM) and cardiovascular disease (CVD).

The findings presented highlight the ability of apabetalone to block some of the detrimental effects of poor dietary habits, commonly seen in western diets. The negative effects of this diet have recently been shown to contribute to atherosclerotic CVD, especially in those with DM.  Such a diet, when acted upon by the microbes in the gut (microbiome) gives rise to an abundance of a constituent called trimethylamine (TMA). TMA is the building block for trimethylamine oxide (TMAO), which is a small molecule that potentially causes atherosclerotic CVD.  Apabetalone was found to block the actions of TMAO, with potentially positive effects on CVD. This may help explain, in part, why treatment with apabetalone prevented major adverse cardiovascular events (MACE) in cardiovascular patients, as observed in our phase 2b clinical trials.

The data presented at the EASD extends our knowledge of how apabetalone may counter the pathology underlying poor outcomes in cardiovascular disease.  Additionally, our current data fits well with the newest thinking in the field of DM that questions whether the one-target approach of controlling blood glucose alone in patients with DM (Rodriguez-Gutierrez and Montori 2016) is sufficient. Many studies have now demonstrated that in patients with both DM and CVD together, their disease arises from not one but multiple factors and intersecting pathways. Thus, simply focusing on one parameter such as glucose, as suggested by current guidelines for treating DM, may not yield significant benefit. The most recent paradigm shift is that the treatment of multiple risks including the classical parameters such as; glucose, lipids, blood pressure, along with newer targets, will not only be necessary, but will likely be more successful.

The eVideo link to Dr. Wong’s EASD presentation can be accessed here:


Rodriguez-Gutierrez, R. and V. M. Montori (2016). “Glycemic Control for Patients With Type 2 Diabetes Mellitus: Our Evolving Faith in the Face of Evidence.” Circulation. Cardiovascular quality and outcomes.




Resverlogix recently participated in the symposium, Epigenetics: Cancer and Beyond, at the New York Academy of Sciences. An international assembly of biomedical investigators convened to explore the therapeutic potential of pharmacologic modulation of the epigenome. Abnormalities in the epigenome have been identified in many diseases, providing a promising new path for drug discovery. Internationally renowned expert in the field of cancer research, Dr. Craig B. Thompson, Memorial Sloan Kettering Cancer Center, delivered the keynote address at the symposium which was chaired by Dr. Norman Wong, Resverlogix’s Chief Scientific Officer and Dr. Dominique Verhelle of Third Rock Ventures. Dr. Ewelina Kulikowski, Senior Vice President of Research & Development presented on behalf of Resverlogix. Additional speakers included: Dr. Michael Elowitz, California Institute of Technology, Dr. Keiko Ozato, National Institute of Child Health and Human Development, Dr. Roberto Pili, Indiana University School of Medicine, Dr.Patrick Trojer, Constellation Pharmaceuticals, Dr. Christopher Vakoc, Cold Spring Harbor Laboratory, Daniel Vitt, 4SC AG, and Dr. Eric Campeau, Zenith Epigenetics.

The Epigenetics: Cancer and Beyond eBriefing is now posted to the Academy website. It is open to the public and can be accessed at:

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:

More information about the Richmond Club can be found at:

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:


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.