By John Vandermosten, CFA

We are initiating coverage of Resverlogix Corp. (RVX.TO) with a CAD$5.00 price target based on our estimates of a 2020 launch of RVX-208 (apabetalone) in Europe and Latin America, followed by a launch in the United States and in partner markets for reduction of major adverse cardiovascular event (MACE) in high-risk populations.

Resverlogix is a clinical stage cardiovascular company with an epigenetic platform technology that modulates protein production. Novel compounds arising from Resverlogix's epigenetic drug development platform function by inhibiting Bromodomain and Extra Terminal domain (BET) proteins and have the potential to impact multiple biologies and diseases. Resverlogix is engaged in the development of novel therapies for important global medical markets in a variety of broad areas of cardiovascular disease (CVD), atherosclerosis, neurodegenerative diseases, renal conditions and potentially other orphan indications.

Apabetalone (RVX-208) has a multifactorial approach and impacts several key biological processes that play a role in vascular disease risk. These processes include vascular inflammation, complement, coagulation, vascular calcification, reverse cholesterol transport (RCT) and metabolic mediators.

Apabetalone is the first selective BET bromodomain inhibitor in clinical trials for high-risk vascular disease. Resverlogix is the first to test apabetalone in the reduction of major adverse cardiac events (MACE) in diabetic and chronic kidney disease (CKD) patients, and has a seven-year head start in the arena of epigenetic small molecules for CVD risk reduction. Analysis of prior Phase 2 clinical trials data (“ASSERT,” “ASSURE,” and “SUSTAIN”) indicated that apabetalone significantly reduces coronary atherosclerosis and major adverse cardiac events in patients with CVD who also have a low level of high-density lipoprotein (HDL) and elevated C-reactive protein (CRP), and other select populations with unmet medical need. Resverlogix is currently underway with its Phase 3 clinical trial “BETonMACE” which seeks to evaluate time to MACE in high-risk type 2 diabetes mellitus subjects with coronary artery disease.

As of January 2016, Resverlogix held approximately USD$30 million in cash on its balance sheet and is spending approximately $2 million per month to fund internal operations, the BETonMACE trial and interest payments. The company carries $41.5 million of debt on its balance sheet which it plans to refinance prior to summer 2017. Resverlogix began enrolling for its Phase 3 BETonMACE trial in late 2015 and while exact expenditures will be based on the total number of patients enrolled, Resverlogix has guided trial costs to be in the range of $45 to $50 million over the anticipated three year duration.

Based on the anticipated length of the trial, the announcement of top-line data is expected to be in late 2018, with subsequent filing of a new drug application (NDA). The company will initially pursue an approval in Europe and Latin America followed shortly after by a filing in the United States. Resverlogix also has a relationship with Hepalink in China and Taiwan which would provide for additional licensing revenue from sales in Asia.

INVESTMENT THESIS

Cardiovascular disease (CVD) is the number one killer in both North America and the world. With estimated costs of $300 billion in the United States and almost $900 billion worldwide, there is an intense demand for therapies that will address this very important disease. In developed countries, there is an accelerating demographic trend of growth in the older population. Given the high degree of correlation between age and heart disease, as we see faster growth in the developed world’s older population, the globe will also experience a substantial increase in heart disease. Based on US Census Bureau data, in just the United States alone, the over 60 population will increase from 69 million in 2016 to over 111 million in 2050. This is a 61 percent increase over this time period and a rate that is double the overall population growth rate.

Besides age, several other risk factors for heart disease have increased over time including obesity, diabetes and high cholesterol. These risk factors are expected to increase the incidence of heart disease in the population, which suggests that the incidence of heart disease will grow even faster than the rate of the aging population.

The need and demand for cardiovascular disease treatment is immense and is expanding. The current slate of therapies have only modestly addressed underlying problems, leaving substantial opportunity for therapies that are more effective and address a wider list of underlying biologies.

Resverlogix’s lead compound, apabetalone has shown promise in addressing many of the key biomarkers underlying CVD and potentially has applications in other therapeutic areas beyond CVD. The drug is currenly in Phase 3 trials for high risk cardiovascular disease and the company has indicated that there are renal and orphan indications that merit clinical investigation on the horizon, potentially expanding the addressable market for apabetalone. Based on the many completed studies for the compound, there is evidence that it has a positive impact on several key biologies that are behind CVD risk such as vascular inflammation, complement, coagulation, vascular calcification, RCT and metabolic mediators.

Given the substantial size of the population that is anticipated to suffer from CVD, and the dramatic costs that are expected to be incurred, there is an acute need for therapies to address the growing problem. Even with competing therapies, many of which have not shown promising levels of efficacy or safety, there is a materially large niche for a number of treatements for CVD in the era of personalized medicine. The promising clinical evidence for Resverlogix’s apabetalone is supportive of an investment in the company’s stock.

In the following sections we provide additional detail regarding the impact of CVD. We further elaborate on the etiology of the disease and provide a backdrop for the method of action for RVX’s lead compound. A review of competing therapies is also provided.

Background on Epigenetics

Biologist Conrad Waddington first defined the term epigenetics in the 1940s as the branch of biology which studies the causal interactions between genes and their products which bring the phenotype into being (Waddington, 1942). In other words, epigenetics refers to the study of heritable changes caused by activation or deactivation of gene expression that do not involve alterations in DNA sequence (Dupont et al., 2009).

Epigenetics is involved in many normal cellular processes. Epigenetic modifications to DNA or DNA associated proteins (histones) can turn a gene on or off and determine if its activity is high or low, thus dictating which proteins are subsequently transcribed (Simmons, 2008). Examples of these epigenetic modifications include acetylation, methylation, and phosphorylation. These modifications are added to histones by enzymes known as “writers” and removed by enzymes referred to as “erasers.”

Over the last decade, early epigenetic approaches focused on these “writers” and “erasers” which involved chemical-to-chemical interactions. One way to turn genes off is via epigenetic silencing, by DNA methylation, histone modifications, and/or RNA-associated silencing, possibly leading to variable expression. The most popular epigenetic therapies aim to reactivate genes that have been silenced via inhibition of histone acetylation and/or DNA methylation (Egger et al., 2004). A more advanced approach to epigenetics involves the protein-to-protein interaction of “readers,” which are proteins that that identify a specific pattern of modifications by binding to them and recruiting other proteins to modulate gene activity. For instance, as BET proteins bind, they recruit additional proteins to regulate gene activity. Once the gene becomes activated, messenger ribonucleic acid (mRNA) is synthesized followed by the translation of mRNA into a specific protein.

Epigenetic therapy is emerging as a promising area of biotechnology/medical research and drug development poised to combat diseases of high unmet clinical need. Epigenetic therapy is currently being explored to target cardiovascular, neurological and metabolic diseases, with emphasis on protein and enzyme molecular targets. Since there is evidence that these epigenetic changes are involved in many disease processes, such as certain cancers and certain types of mental retardation, this field has become an area of marked research interest (Egger et al., 2004). However, successful epigenetic therapies must be highly selective towards abnormal cells; otherwise, the activation of gene transcription in healthy, normal cells could render them malignant. Although this is quite a feat, researchers are exploring new ways of targeting atypical cells. Since epigenetic modifications play significant roles in the regulation of cellular processes and in overall health, epigenetics as a field is quickly growing and continues to look promising for the discovery of new medications (Simmons, 2008). The discovery by Resverlogix that RVX-208 is a BET bromodomain inhibitor adds new drive to the promise of epigenetic mechanisms as a source of new therapeutics in order to combat the area of high-risk CVD and other diseases that are impacted by this pathway.

Resverlogix’s Epigenetics Platform Technology

The basis of Resverlogix’s epigenetics drug development platform involves targeting Bromodomain and Extra Terminal Domain (BET) proteins with the potential to impact cardiovascular disease, neurodegenerative diseases, diabetes, cancer, and autoimmune diseases. Acetylated lysine, a modified amino acid that is found in histones, binds to the two small bromodomain regions of BET proteins. Resverlogix has discovered BET protein inhibitors that specifically bind to BET bromodomains, thereby preventing them from binding to histones. This leads to modifications in certain gene activity involved in disease processes. Resverlogix is focusing the majority of its research efforts on the BRD2, BRD3, BRD4, and BRDT proteins.

These novel, small molecule compounds identified by Resverlogix function via selective inhibition of BET proteins. They alter the activity of genes that play a key role in disease in relevant cell models, demonstrate oral bio-availability allowing for oral administration in the form of a pill, and demonstrate activity in animal models of human disease. Resverlogix is in the process of identifying and developing compounds for additional clinical indications with proprietary platform activities continuing to add to its growing portfolio of intellectual property needed to support the development of these assets.

Apabetalone (RVX-208) is a BET antagonist

Resverlogix’s lead candidate, apabetalone, is a first-in-class, orally active small molecule that selectively inhibits BET proteins.

Apabetalone works by binding to the two specialized areas of BET proteins known as bromodomains (BD1 and BD2). Both of these bromodomains can recognize and bind to an acetylated lysine, which is a modified amino acid found on histones bound to DNA. This process is referred to as “reading”, which refers to the protein-to-protein interaction of a BET protein finding and binding an acetylated lysine through the actions of the bromodomain. Apabetalone acts via an epigenetic mechanism on BET proteins, specifically BRD2, BRD3, BRD4 and BRDT with increased selectivity for BRD4-BD2.

By targeting BET bromodomains, apabetalone has a multimodal approach and impacts several key biological processes that play a role in vascular disease risk. Initially, apabetalone binds to the BET protein and triggers a cascade of events. Apabetalone induces Apo A-1 mRNA production in human hepatocyte cell lines leading to an increase in Apo A-1 gene transcription and eventually an increase in endogenous Apo A-1 protein production (McLure et al., 2013). This results in the subsequent synthesis of new HDL particles.

Apabetalone Targeting Apo A-1, HDL, & Reverse Cholesterol Transport

Apo A-1 makes up approximately 70% of the protein found in HDL particles (“good cholesterol”) and is secreted by the intestines and liver. Apo A-1 is crucial for the synthesis and function of HDL (Zannis et al., 2006), and greater production of Apo A-1 results in the formation of new HDL molecules. The newly formed HDL molecules have increased functionality because they are unfilled and flat, and thus have a greater ability to remove cholesterol out of plaques from arteries and reduce and/or prevent atherosclerosis. These HDL particles can effectively remove plaque via RCT, which is a natural physiologic process by which cholesterol is transported out of arteries and subsequently to the liver for excretion out of the body in bile.

Apabetalone Targets Multiple Biologies

For the first several years of RVX-208 development, Resverlogix focused solely on the RCT mechanism for MACE reduction, and although it is plays an important role in the process, management has now evolved the company’s focus to address other aspects of the drug’s mechanism of action that are impacted thorough the BET Bromodomain 4 target. Resverlogix believes that apabetalone:

These multimodal aspects of apabetalone explain the overall MACE reduction observed in certain populations within back-to-back clinical trials.

The Apabetalone Hypothesis

In April 2012, Resverlogix announced the mechanism of action by which apabetalone increases Apo A-1 production. The finding provides the opportunity to initiate licensing and partnering in the areas of atherosclerosis, oncology, autoimmune and Alzheimer's diseases where the MoA plays a pivotal role. The value can be further translated into the cancer space, with the connection highlighted by Dr. James Watson between regulation of the BRD4 protein and its relationship with uncontrolled cell division by AML cells.

Apabetalone disrupts the acetylation of specific lysines in the histones found in actively transcribed regions of DNA. The compound is taken up by liver cells, where it binds to a BET protein. The proteins contain two small conserved regions called bromodomains, each of which has a pocket that can bind to or read specific acetylated lysine found at the end of some histones. When this interaction occurs, a different region of the BET protein can recruit other components important for controlling gene transcription. When a BET protein is anchored to chromatin via its bromodomain binding to an acetylated lysine, this complex recruits additional proteins that regulate transcription which can lead to selective increases and decreases in mRNA. Apabetalone binds to the same pocket of the bromodomain as the acetylated lysine of histones and in so doing causes the BET protein to be released from chromatin, thus altering transcription. This action of apabetalone leads to an increase of Apo A-1 mRNA and production of Apo A-1 protein, the key building block of new HDL.

Researchers recognize that high concentrations of plasma HDL are a negative risk factor for coronary heart disease (CHD) and we cite the well-known Framingham study as early evidence (Gordon et al., 1977). Therefore, novel therapies that consistently increase Apo A-1 and HDL to facilitate plaque removal and regression are clearly intriguing. There are a limited number of companies pursuing programs that focus on enhancing Apo A-1. The Medicines Company and Roche are developing recombinant proteins or peptides that exogenously increase Apo A-1. However, these therapies are costly to manufacture and may cause immunological responses for patients when used for longer durations. Therefore, these therapies are likely to have utility as acute or induction-based therapies.

Drugs that target Apo A-1 production and cholesterylester transfer protein (CETP) inhibitors are the only technologies to date that were thought to effectively eliminate and regress atherosclerotic plaque from arteries in high-risk CVD patients. CETP inhibitors are a class of drugs that work by reducing the risk of atherosclerosis by increasing HDL and RCT. To date, these drugs have generally failed in trials either because of excess deaths (Pfizer’s torcetrapib), not showing clinically meaningful efficacy despite increases in HDL (Roche’s dalcetrapib) or for high-risk atherosclerotic cardiovascular disease (Eli Lilly’s evacetrapib).

The other CETP inhibitor currently being tested, Merck’s anacetrapib, exhibited encouraging Phase 2b interim results in 2010. The compound is currently participating in two Phase 3 trials that will run until 2017. Apabetalone’s ability to increase Apo A-1 production and thus enhance RCT activity could set itself apart from other HDL medications, making it an intriguing candidate for the treatment of atherosclerotic CVD. While the Phase 3 trial is still in process for apabetalone, management believes that the drug is positioned to be one of the most promising drugs in development for the prevention and reduction of atherosclerotic related CVDs.

Currently, apabetalone is the first and most clinically advanced BET bromodomain inhibitor in clinical trials for high-risk vascular disease. Management also noted that apabetalone is the first ever and only drug with selectivity for the BRD4-BD2 bromodomain that has been written up by the Structural Genomics Consortium (Picaud et al., 2013). Management also believes the drug has the advantage of a seven-year head start on any other drug in this category.

Addressing the Unmet Need in CVD

Cardiovascular disease is the most common cause of death in the world and future projections illustrate that the prevalence of CVD and associated expenses are anticipated to rise dramatically over the next decades. The need for new therapeutics that lower the CV risk is crucial to addressing this unmet clinical need. With the growing knowledge and insight into disease mechanisms, new approaches are being evaluated with the hopes of the discovery of novel therapeutic options for CVD.

Resverlogix is addressing the major problem of the unmet need in cardiovascular management. Over the last several years, there has been a great movement forward in cardiovascular care with statins and other therapies, but these address less than a third of the afflicted population. There are new medications emerging such as the novel LDL modulators like PCSK9 that are designed to lower LDL, yet they only have a small impact on the unmet need in CV management and take up only a small part of the market.

The large market opportunity lies in the 70% of unmet need of unmanaged cardiovascular issues that extend to other indications such as diabetes and kidney disease. According to the International Diabetes Federation, there are 387 million patients worldwide with diabetes, and this number is expected to rise to 592 million by 2035. While the majority of current therapies aim to manage glucose levels in diabetic patients, Resverlogix is taking a unique approach by looking at it from the point of view of reducing MACE – the primary killer in both men and women. In a multinational study, 50% of people with diabetes died of cardiovascular disease, primarily heart disease and stroke (Moorish et al., 2001). Other sources cite up to 80% of patients with diabetes will develop and possibly die from CVD (Narayan et al., 2003 and Hogan et al., 2003). Furthermore, CKD is an extension of diabetes and also results in high CVD death rates, and may be another area addressed by apabetalone.

Major Adverse Cardiac Events (MACE)

Many scientists, key opinion leaders and physicians believe that of all the markers that are analyzed for providing prognostic predictability for cardiovascular risk, MACE is the most crucial. Payer groups and health systems carefully assess MACE when looking at the potential reimbursement of a novel CVD drug. MACE includes several key markers of cardiovascular risk including death, myocardial infarction, stroke, hospitalization for cardiac-related incidents, percutaneous stent procedures, worsening angina, worsening of peripheral artery pain and ischemia. According to the 2015 AHA Statistics report, an estimated 85.6 million American adults (greater than 1 in 3) have one or more types of CVD. Many of these CVD patients will have some type of MACE during or after they have been diagnosed with heart disease. On average, more than 2,150 Americans die of CVD daily, which is approximately 1 death every 40 seconds (Mozaffarian et al., 2015).

The term MACE came into use in the mid-1900s in reference to complications related strictly to percutaneous coronary interventions (PCIs) in hospital settings (Hermans et al., 1993 and Keane et al., 1994). Although there is no standard definition of MACE, it has become the most commonly utilized end point in cardiovascular clinical research today, and is reported for both short and long term outcomes involving various treatment regimens. MACE is used today as a composite of clinical events that typically include safety and effectiveness endpoints. There has been some controversy over the last decade within the medical community regarding the true value of MACE in clinical trials, as there is no standard definition for MACE and individual outcomes vary per study and inconsistencies often arise (Kip et al., 2008). In response, as part of its trial design Resverlogix has provided both a narrow and broad definition of MACE as primary and secondary outcome measures.

Clinical Overview of Apabetalone

Resverlogix has completed many clinical trials to date. Apabetalone has been tested in over 1,000 patients in 12 countries, and clinical experience with apabetalone has demonstrated that BET inhibitors can be both safe and effective. Over the years, Resverlogix has gathered information from these studies and shifted focus to target patients with low HDL and diabetes with co-treatment of RVX-208 and rosuvastatin (Crestor®) and atorvastatin (Lipitor®) in its BETonMACE trial.

Prior to the BETonMACE trial, apabetalone has completed two Phase 2b trials named SUSTAIN and ASSURE in collaboration with the Cleveland Clinic. Furthermore, Resverlogix has performed thorough analysis of MACE in the Phase 2b clinical program; 35 MACE events were reported in both the SUSTAIN and ASSURE trials. This analysis demonstrated that treatment with apabetalone was associated with a 55% reduction in MACE. Apabetalone treated patients had a lower level of cumulative events of 6.7% vs. 15.1% (p=0.02) in the placebo treated group. Furthermore, a beneficial effect of apabetalone on patients with diabetes mellitus was accentuated with a reduction in MACE that was lowered by 77% (p=0.01). BETonMACE will continue to focus on MACE reduction as the primary endpoint for the registration study.

Phase 3 “BETonMACE”

In October 2015, Resverlogix launched its Phase 3 “Effect of RVX-208 on Time to Major Adverse Cardiovascular Events in High-Risk Type 2 Diabetes Mellitus Subjects with Coronary Artery Disease” (BETonMACE) trial with lead drug apabetalone in high-risk patients with coronary artery disease (CAD) and type 2 diabetes mellitus (DM). The study is a large international multi-center, double-blind, randomized, parallel group, placebo-controlled clinical trial to determine whether treatment with apabetalone in combination with rosuvastatin or atorvastatin increases the time to MACE compared to treatment with rosuvastatin or atorvastatin alone.

The primary endpoint of the BETonMACE trial is designed to show a relative risk reduction of MACE, narrowly defined as a single composite endpoint of CV death, non-fatal myocardial infarction (“MI”) and stroke. The study is an event-based trial and will continue until at least 250 MACE events have occurred. MACE will be adjudicated by an independent committee and the study will be monitored by a data safety monitoring board. Management is seeking a 30% reduction in MACE as compared to the placebo arm.

Secondary endpoints include time to first occurrence of the composite broad MACE which includes the addition of hospitalization for CVD events (unstable angina and revascularization procedures), changes in lipoprotein concentrations (HDL and apolipoprotein A-1, changes in diabetes mellitus variables (glucose and glycated hemoglobin), change in alkaline phosphatase (“ALP”), changes in kidney function and additional safety and tolerability of apabetalone.

In order to be eligible to participate in the study, patients must have documented history of type 2 Diabetes Mellitus, experienced a recent (defined as 7-90 days prior to randomization) coronary artery disease (“CAD”) event including unstable angina, revascularization procedure or MI and have low levels of HDL (

Resverlogix believes that a Phase 3 MACE trial could confirm health benefits in CVD, diabetes, and CKD. The main objective of the trial will be to confirm MACE reduction by apabetalone as observed in SUSTAIN and ASSURE pooled analysis and also expand safety assessment. The study will be in a larger prospective setting with high-risk patients that have diabetes mellitus and low HDL-C (< 40 mg/dL for males and < 45 mg/dL for females who are post events). Management also plans to further explore the potential impact that apabetalone may have on inflammation, the complement and coagulation pathways, as well as on platelet improvement in these high-risk patients in the future Phase 3 trial.

As part of the BETonMACE trial, the study will examine a subset of the patients to test for impact on neuro-degenerative diseases and test for cognition. The subset will include patients over the age of 70 and perform a Montreal Cognitive Assessment (MoCA) test. The company anticipates that this could be from 200 to 300+ participants in the trial. This population group is the equivalent of a Phase 2 dementia trial built into BETonMACE.

BETonMACE will initially be conducted in Argentina, Mexico and various European cities with potential expansion into Asia through the partnership with Hepalink. U.S. sites are also a consideration as Resverlogix looks towards FDA approval in this adaptive trial that will target 2,400 patients.

VALUATION AND RECOMMENDATION

We are initiating coverage of Resverlogix Corp. (RVX.TO) with a price target of CAD$5.00. Resverlogix’s lead clinical stage candidate, apabetalone, is the first selective BET bromodomain inhibitor in clinical trials for high-risk vascular disease. Apabetalone is targeting a very specific patient population with low HDL, diabetes and chronic kidney disease with a high cardiovascular risk for increased MACE. Based on internal analysis conducted by Resverlogix, there are from 3.0 to 4.0 million CVD patients with low HDL and recent ACS in the initial targeted markets of Europe and Latin America. Our research estimates that there are a similar range of these patients in the United States. Resverlogix analysis also shows from 1.8 to 2.0 million individuals with CKD and ACS (non-dialysis) are also potential patients for apabetalone. Our analysis shows a slightly greater number of these individuals in the United States.

Our pricing is dependent on geography, and we select a range slightly narrower than that suggested by the company’s analysis. We estimated that apabetalone will be priced between $3,000 and $4,000 per year, but note that increased levels of efficacy shown in the BETonMACE trial may support pricing upside from current levels.

We also value the licensing agreement with Hepalink and assume that the addressable market will be between two and three million patients and that Hepalink will achieve from 40% to 50% penetration into this market. Pricing for the annual regimen is expected to range from $1,200 to $1,500. Hepalink will pay Resverlogix a royalty equal to 6% of revenues as well as milestone payments over the duration of the agreement.

To value Resverlogix, we use a discount rate of 15%, as we do with other Phase 3 candidates under our coverage and we apply a 64% probability of success in EU, Latin America and US markets, which is guided by the probability of approval observed by Phase 3 candidates at the FDA. We initially anticipate approval by the regulatory agencies in Europe in 2020, followed shortly after by approval in Latin American geographies and the United States in 2022. For China and other Hepalink markets, we assume a 2022 launch and a 50% probability of success due to the shorter history and higher degree of uncertainty related to the China Food and Drug Administration (CFDA) approval process.

We initially forecast penetration rates of 1% increasing to 10% into the indicated populations over a multi-year period in the European, Latin American or the United States markets. We assume higher penetration in Hepalink’s addressable markets, which are expected to peak in the 40% to 50% range. The drug may also address orphan indications which may expand the population. We anticipate that Resverlogix will use partners to market and sell apabetalone and will pay the company a royalty (which includes milestone payments) from 15% to 20%. The agreement with Hepalink provides a lower 6% royalty payment, but also requires the payment of milestones and demands that Hepalink conduct clinical trials and secure approval from the appropriate regulatory agencies in the Asian territories under its license.

For reference, we highlight the existing market for at risk CVD patients, including approved drugs like Lipitor® ($13.7 billion peak in 2006), Crestor® ($6.6 billion peak in 2011, $5.5 billion in 2014), Lovaza ($1.1 billion peak in 2013). We are also using several estimates we found for late-stage clinical candidates such as Amgen’s and Regeneron/ Sanofi’s PCSK9 inhibitors, evolocumab and alirocumab, respectively. Wall Street consensus estimates, as well as independent analyst estimates from websites such as TheStreet.com, FierceBiotech, Benzinga, and Seeking-Alpha, for these drugs range between $3 billion to $10 billion. We believe apabetalone, although not nearly as well known in the investment community compared to these other compounds, has similar sales potential and we conservatively forecast a peak of over $6 billion in 2026 and 2027 for the markets we are currently considering.

We assume that Resverlogix will refinance its $41 million in debt due August 28, 2017 on similar terms as current, which are Canadian one-year LIBOR swap rate plus 3.14%.

Based on our assumptions above our valuation target is CAD$5.00 per share.

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• Reduces key vascular inflammation markers

• Modulates the complement, coagulation and acute phase response cascades, known drivers in CVD and acute cardiac events

• Enhances RCT

• Lowers key markers of metabolic risk