Glossary

A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z |

A

ABCA means the Business Corporations Act (Alberta).

Acetylated Lysine an acetyl-derivative of the amino acid lysine (also known as Acetyllysine). In proteins, the acetylation of lysine residues is an important mechanism of epigenetics. It plays a role in regulating the transcription of genes through recruitment of additional proteins to histones associated with DNA.

Acetylation the process by which an acetyl functional group is transferred onto a molecule

Acute Coronary Syndrome (“ACS”) a term used for any condition brought on by the sudden reduced blood flow to the heart. Acute coronary syndromes may include a heart attack, unstable angina. The first sign of acute coronary syndrome can be sudden stopping of your heart (cardiac arrest). Acute coronary syndrome is often diagnosed in an emergency room or hospital.

Acute Phase Response Cascade a series of systemic events that occur within hours of an inflammatory stimulus. The most important component of this response comprises the acute phase proteins. Acute phase response takes place in response to a variety of stimuli including bacterial infection, trauma and myocardial infarction.

Adjudication of major endpoints by a clinical endpoint adjudication committee (CEC) is necessary to provide standardized, systematic, independent, and unbiased assessments of endpoints in clinical investigation. During trial planning, the events classification strategy being considered may also have an important impact on estimation of event rates and the calculations of sample size and power. Education and training of clinical investigators regarding end‐point definitions and ascertainment, proper completion of trial documentation, and the need for adequate source documentation, may help in minimizing differences between CEC and site investigator assessments of endpoints. The strategy and rigor of the clinical event adjudication process used may influence the interpretation of trial results.

Alkaline Phosphatase (“ALP”) a hydrolase enzyme responsible for removing phosphate groups from many types of molecules, including proteins. Data suggests that elevated serum alkaline phosphatase levels are associated with increased mortality and morbidity in diseases such as diabetes, chronic kidney disease, heart failure and Alzheimer’s disease.

ALTs Alanine transaminase, also called serum glutamic pyruvic transaminase (“SGPT”) or alanine aminotransferase (“ALAT”), is found in serum and most commonly associated with the liver, measurements are used as a part of a diagnostic evaluation of hepatocellular injury.

Alpha1 HDL mature lipid-rich particles that are involved in reverse cholesterol transport whereby cholesterol is removed from cell membranes to the liver for excretion.

Alzheimer’s disease (“AD”) a disease marked by the loss of cognitive ability, generally over a period of 10 to 15 years, and associated with the development of abnormal tissues and protein deposits in the cerebral cortex.

Angiography a medical imaging technique used to visualize the inside (lumen) of blood vessels and organs of the body, with particular interest in the arteries, veins and the heart chambers.

Antibody is a protective protein produced by the immune system in response to invading foreign particles (antigens) that may cause harm or infection.

Apabetalone (RVX-208) is a leader in a new class of drugs designed to regulate disease-associated proteins.

Apolipoprotein the protein combined with a lipid to form a lipoprotein, a component of HDL and LDL.

ApoA-I is the apolipoprotein component of the HDL particle.

ApoB is one of the apolipoprotein components of the LDL particle.

Atherosclerosis a disease in which the deposition of lipids and plaque in arteries results in the hardening and decrease of arterial lumen size.

Atherosclerotic Plaque the deposit or accumulation of lipid containing plaques in the arterial wall (also known as atheroma).

B

BD1 and BD2 refer to the two bromodomain binding pockets of BET proteins which interact with acetylated lysine residues on histones. BD1 and BD2 have slightly different structures, shapes, and binding properties.

BET proteins (Bromodomain and ExtraTerminal domain)proteins that contain bromodomains, which regulate gene transcription through binding to acetylated lysines within the histones bound to DNA.

Beta Amyloid Plaque an aggregation of Beta Amyloid, a peptide of 39–43 amino acids. Beta Amyloid appears to be the main constituent of amyloid plaques in the brains of Alzheimer's disease patients. These plaques are composed of a tangle of regularly ordered fibrillar aggregates called amyloid fibers, a protein fold shared by other peptides such as the prions associated with protein misfolding diseases.

BETonMACE is a global phase 3 clinical trial designed to determine whether bromodomain and extra-terminal domain (BET) inhibition by apabetalone increases the time to major adverse cardiac event (MACE) in high-risk type 2 diabetes mellitus patients with coronary artery disease. Full study protocol can be found HERE.

BETonRENAL is a planned clinical trial for examining the efficacy and safety of bromodomain and extra-terminal domain (BET) inhibition by apabetalone in renal disease patients. Study protocol will be defined in conjunction with BETonMACE data in this patient population.

b.i.d. “bis in die" (Latin) refers to twice a day dosing.

Bioavailability the degree and rate at which a drug is absorbed into a living system or is made available at the site of activity after administration.

Biopharmaceuticals a medical drug developed by biotechnology to improve human or animal health.

Bromodomain and Extra-Terminal Domain (BET) family of proteins is made up of BRD2, BRD3, BRD4, and BRDT, characterized by the presence of two tandem bromodomains and an extra-terminal domain. BET proteins are epigenetic “readers” which play a crucial role in regulating gene transcription through binding interactions between their bromodomains and epigenetic marks (acetylated lysine residues) on histones, and recruitment of other cellular components necessary for gene transcription.

C

Cancer a disease characterized by abnormal and uncontrolled cell growth.

Coagulation Cascade are a series of events that culminate in the formation of a blood clot and its subsequent breakdown. This process is controlled by a signaling cascade consisting of coagulation factors which interact and activate each other.

Complement Cascade is the complement system contains a network of tightly regulated proteins that together are a key part of the innate immune system response. The principal roles of complement include defending against invading pathogens, bridging innate and adaptive immunity, eliminating immune complexes and the products of inflammatory injury. 

Coronary artery disease ("CAD") the most common type of heart disease. It is the leading cause of death in the United States in both men and women. CAD occurs when arteries that supply blood to heart muscle become hardened and narrowed. This is due to the buildup of cholesterol and other material, called plaque, on their inner walls.

C-Reactive Protein ("CRP") is a biomarker of cardiovascular inflammation.

Cardiovascular Disease (CVD) a group of diseases of the heart and blood vessels.

Cholesterol a fatty molecule essential for normal body functions,
including the production of hormones and bile acids; it is also an important component of a cell membrane.

Compound a chemical substance formed from two or more elements (also see drug).

Contract Research Organization ("CRO") an organization (commercial, academic or other), contracted by the sponsor to conduct research or development activities.

Chromatin the combination of DNA and proteins that make up the contents of the nucleus of a cell. The primary functions of chromatin are: to package DNA into a smaller volume to fit in the cell, to strengthen the DNA to allow mitosis and meiosis and prevent DNA damage, and to control gene expression and DNA replication. The primary protein components of chromatin are histones that compact the DNA.

Clinical Trial/Study a research study in human subjects to evaluate a new drug, medical device, biologic or other intervention under a strictly controlled scientific setting.

Chronic Kidney Disease (“CKD”) is a progressive loss in renal function over a period of months or years, also known as chronic renal disease (CRD). Chronic kidney disease is also associated with other chronic diseases such as diabetes and or cardiovascular disease. Profession guidelines classify the severity of chronic kidney disease in five stages, with stage 1 being the mildest and usually causing few symptoms and stage 5 being a severe illness with poor life expectancy if untreated. Stage 5 CKD is often called end stage renal disease.

D

Deoxyribonucleic Acid (“DNA") the material inside the nucleus of cells that carries genetic information.

Diabetes Mellitus is the most common metabolic disease and currently is a worldwide epidemic fueled by the wave of modernization swiping across much of the developing countries. There are two types of diabetes, Type-1 and Type-2. The difference between these two types of diabetes is that there is an absence of insulin (Type-1) or a deficiency in the amount of insulin (Type-2). While Type-1 affects less people and mostly younger individuals, Type-2 most commonly accounts for roughly 90% of the cases. The cause of Type-1 Diabetes is believed to lie in defects within the immune system. In the pathogenesis of Type-2, there is direct connection between dietary habits, sedentary life styles and obesity. One of the most feared consequences of either form DM is that it is one of many major risk factors leading to the development of CVD, the number one cause of premature death in modern societies.

Drug any substance that can be used to modify a chemical process or processes in the body to mitigate, treat or prevent a medical condition.

Dyslipidemia a disorder associated with abnormal levels of blood lipids and lipoproteins.

E

End Stage Renal Disease (“ESRD”) is the last stage of chronic kidney disease. The stage at which the kidneys have incurred permanent damage and lost nearly all function and the treatments include dialysis or a transplant.

Endogenous a process whereby a molecule is produced within the body.

Enzyme a protein that acts as a catalyst in mediating and accelerating a specific chemical reaction.

Epigenetics the study of heritable traits not caused by a change in the genetic code. These are typically mediated through secondary modifications to the DNA and its bound proteins, which regulate expression of genes contained within the DNA.

Estimated Glomerular Filtration Rate ("eGFR") is a rate calculated using the results of a blood creatinine test, age and gender. The result indicates the severity and stage of chronic kidney disease. An eGFR below 60 for three months or more indicates CKD.

F

Food and Drug Administration (FDA) is the United States governmental agency responsible for the approval, manufacture, usage and sale of food, human diagnostics and therapeutic products.

G

Gene a sequence of DNA encoding a protein.

H

High-density Lipoprotein (HDL) a complex of lipids and proteins (ApoA-I) that function in the transport of cholesterol away from the tissues to the liver and is associated with a decreased risk of atherosclerosis and coronary heart disease (also known as “good cholesterol”).

Histones highly alkaline proteins found in eukaryotic cell nuclei that package and order the DNA into structural units called nucleosomes. Histones are the chief protein components of chromatin, acting as spools around which DNA winds, and play a role in gene regulation.

Health Canada the governmental agency which regulates the manufacture, use and sale of human diagnostics and therapeutic products in Canada, and oversees safety of foods.

Hepatic Transaminases variables analyzed in plasma that describe liver function and liver cell integrity. They include, for example, Alanine Transaminase (“ALT”) and Aspartate Transaminase (“AST”).

I

Interleukin 6 (“IL-6”) is an inflammatory mediator that acts in many diseases as a pro-inflammatory cytokine. IL-6 is known to stimulate the inflammatory and auto-immune processes in many diseases such as diabetes, atherosclerosis, Alzheimer’s disease and rheumatoid arthritis.

Investigational New Drug (IND) the application submitted to the FDA prior to being tested in humans in clinical trials.

Intravascular Ultrasound ("IVUS") an invasive procedure, performed along with cardiac catheterization; a miniature sound probe (transducer) on the tip of a coronary catheter is threaded through the coronary arteries and, using high-frequency sound waves, produces detailed images of the interior walls of the arteries. Where angiography shows a two-dimensional silhouette of the interior of the coronary arteries, IVUS shows a cross-section of both the interior, and the layers of the artery wall itself.

L

Low-density Lipoprotein (LDL) a complex of lipids and proteins (ApoB) that function by transporting cholesterol to the tissues, in particular the arteries, and is associated with an increased risk of atherosclerosis and coronary heart disease (also know as “bad cholesterol”).

Lipids are fatty substances, including cholesterol and triglycerides that are present in cell membranes and body tissues.

Lipoproteins a complex of proteins and lipids that are the principal means by which fat and cholesterol is transported in the blood; major lipoproteins are low-density lipoproteins (LDL) and high-density lipoproteins (HDL).

M

Major Adverse Cardiac Event ("MACE") is a commonly used end point for cardiovascular research. MACE is a composite of clinical events that usually are measured in clinical trials of cardiovascular patients. It may include a variety of end points such as death, myocardial infarction (heart attack), stroke, worsening angina, hospitalization for heart disease and operative treatments for heart disease.

Metabolism the biochemical modification or degradation of a drug, often readily removing the drug from the body.

Methylation is the process by which an methyl functional group is transferred onto a molecule.

N

New Drug Application (“NDA”) the documentation submitted to the FDA, Health Canada or other local regulatory authorities to obtain approval to market a new drug.

New Drug Submission (“NDS”) : (see “New Drug Application”)

P

Pharmacodynamics the study of the biological actions of a drug in the body, specifically the relationship between how much drug is present and its effects.

Pharmacoeconomics the scientific discipline that compares the value of one pharmaceutical drug or drug therapy to another. It is a sub-discipline of Health economics. A pharmacoeconomic study evaluates the cost (expressed in monetary terms) and effects (expressed in terms of monetary value, efficacy or enhanced quality of life) of a pharmaceutical product.

Pharmacokinetics the study of how a drug is absorbed, distributed, metabolized and eliminated (ADME) by the body over time.

Pharmacology the study of pharmacological agents and their origin, nature, properties and effects on living organisms.

Phase 1 Clinical Trial a smaller scale trial, where a drug is first tested on a small number of healthy human volunteers to evaluate the drug’s safety, schedule, dose, pharmacokinetics and pharmacodynamics (an approximate 1-2 year time trial).

Phase 2 Clinical Trial a study in patients (not healthy volunteers) with the main objective to establish a safe and efficacious dose for phase 3 clinical trials.

Phase 3 Clinical Trial a study or studies in a defined patient population designed to demonstrate effect to support use for a special indication, for example treatment of patients with previous coronary artery disease to prevent the occurrence of a major adverse coronary.

Phosphorylation is the process by which an phosphate functional group is transferred onto a molecule.

Preclinical Studies the studies conducted in animals to evaluate the toxic effects, pharmacokinetics and metabolism of a drug to provide evidence for safety, efficacy and bioavailability of the drug prior to its administration to humans in clinical studies.

R

Reader, writer, eraser are proteins that bind to histone modifications and alter gene activity and protein production (reader); enzymes that add histone modifications (writer); enzymes that remove histone modifications (eraser).

Reverse Cholesterol Transport ("RCT") the term that signifies the process whereby cholesterol, an insoluble molecule, is packaged and transported by special particles in the plasma called lipoproteins for movement from peripheral tissues through the blood and back to the liver for excretion from the body. Cholesterol that moves from peripheral tissues to the liver is considered to be moving in the reverse direction.

RVX-208 our drug candidate for the treatment of atherosclerosis in patients at high risk for cardiovascular disease.

S

Statin a class of drugs that block cholesterol production in the body by inhibiting an enzyme called HMG-CoA reductase.

T

Therapeutic a biopharmaceutical useful for treating a disease.

Toxicology the study of the harmful effects of substances in the body, including the level of toxicity, the mechanism by which toxicity occurs and how it can be controlled.

Therapeutic Products Directorate ('TDP") the Canadian governmental agency that is responsible for the regulation and approval of the sale of drugs and diagnostics in Canada.

Triglycerides a type of fat found in the blood and other parts of the body.

Type II Diabetes (see “Diabetes Mellitus”)

V

 

Z

Zenith refers to Zenith Epigenetics Ltd., which is a clinical stage biotechnology company focussed in oncology. Zenith Epigenetics Ltd. is a wholly-owned subsidiary of Zenith Capital Corp.