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.
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.
Amyloid-beta40 (“A-beta40”) Amyloid beta 40 is one isoform formed by the cleavage of the amyloid precursor protein (“APP”). Along with Aβ42, Aβ40 has been identified in cerebral spinal fluid and plasma and may play a role in the pathology of Alzheimer's disease. Both isoforms are therapeutic targets for AD, and are being studied as experimental biomarkers for the disease.
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.
Apabetalone generic name of RVX-208
Apo Intellectual Property Right any right, whether under a patent, patent application or invention disclosure or otherwise, to use, or to prevent others from using, any product, device, process, substance, composition or service that falls within an ApoA-I Therapeutic Field;
Apo Products are any product, device, process, substance, composition or service that falls within the ApoA-I Therapeutic Field and in respect of which the Company has an Apo Intellectual Property Right;
ApoA-I Therapeutic Field the prevention, treatment or mitigation of any disease via the administration of a Pharmaceutical Agent that results in therapeutic relevant elevation in the plasma levels of ApoA-I that in a predictable model of ApoA-I expression, using either a human or nonhuman primate model, the Pharmaceutical Agent is demonstrated to have at least a seven percent (7%) increase in humans and fifty percent (50%) increase in nonhuman primates in the ApoA-1 plasma level in two consecutive weeks of treatment using less than 30 milligrams – b.i.d. (60 milligrams per day) of the Pharmaceutical Agent per kilogram of the weight of the subject;
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).
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.
b.i.d. “bis in die" (Latin) refers to twice a day dosing.
Bilirubin the yellow breakdown product of normal heme catabolism, that is excreted in bile and urine; elevated levels may indicate a disease state.
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 (see BET proteins)
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.
Common Shares means common shares in the capital of Resverlogix Corp.
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.
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.
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.
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.
Gene a sequence of DNA encoding a protein.
Good Clinical Practice (“GCP”) the international ethical and scientific quality standard for designing, conducting, recording and reporting trials that involve human subjects.
Good Laboratory Practice ("GLP") the international regulation which embodies a set of principles which provide a framework for laboratory studies, ensuring high quality experimental standards and reliable data.
Good Manufacturing Practice ("GMP) the international set of regulations, codes and guidelines for the manufacture of drugs, medical devices, diagnostics and food products.
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”).
IND-Enabling Studies is a toxicology package, including general acute and repeated-dose toxicity and genotoxicity studies, and safety pharmacology studies, conducted under GLP and in accordance with the International Conference of Harmonization guideline (M3(R1)) to support the filing of an IND application (21.CFR.312). Initiation of the toxicology package will occur when protocols have been written and a contract laboratory has been contracted to conduct the studies.
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.
Licensed Know-How are any and all proprietary technology and copyrights owned or controlled by the Company relating to the Licensed Patents, including without limitation, manufacturing processes or protocols, know-how, trade secrets, writings, documentation, data, technical information, techniques, results of experimentation and testing, diagnostic and prognostic assays, specifications, databases, any and all laboratory, research, pharmacological, toxicological, analytical, quality control, pre-clinical and clinical data, and other information and materials, whether or not patentable.
Licensed Product is any product, device, process, substance, composition or service in a Residual Field and which is encompassed within the scope of a Valid Claim.
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).
Major Adverse Cardiovascular Events ("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.
Medical Device a diagnostic or therapeutic article that does not work by chemical action (see DES).
Metabolism the biochemical modification or degradation of a drug, often readily removing the drug from the body.
Method is any method covered by a Valid Claim.
Methylation is the process by which an methyl functional group is transferred onto a molecule.
Net Apo Revenue is the aggregate of the following amounts: (i) amounts received by the Company or its affiliates from any person who is not the Company or its affiliate (a “third party”) in consideration for granting a license or other rights to the third party which entitle the third party to research, develop, make, manufacture, modify, administer, offer to sell, sell or distribute one or more of the Apo Products and/or Apo Intellectual Property Rights or amounts received under the terms of such license or other right that are granted to the third party; (ii) the gross consideration received from a third party by the Company, any licensee or their respective affiliates from the sale of any Apo Product (other than consideration received by the Company, any licensee or their respective affiliates from a licensee of such Apo Product or its affiliate); less (A) credits or allowances, if any, actually granted; (B) discounts actually allowed; (C) freight, postage, and insurance charges and additional special packaging charges; (D) customs duties, and excise sales taxes, duties or other taxes imposed upon and paid with respect to such sales (excluding what is commonly known as income taxes); (E) rebates and chargebacks or retroactive price reductions made to federal, state or local governments (or their agencies), or any third party payor, administrator or contractor, including managed health organizations; and (F) commissions related to import, distribution or promotion of any Apo Product paid to third parties (specifically excluding any commissions paid to sales personnel, sales representatives and sales agents who are employees or consultants of, or members of a contract sales force engaged by or on behalf of, the Company, any licensee or their respective affiliates); and (iii) amounts received from a third party by the Company or its affiliates in consideration for the sale of any Apo Intellectual Property Right.
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”)
Pharmaceutical Agent is a compound or composition covered by a Valid Claim.
Pharmacological Agent (see “Drug”).
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.
Proprotein convertase subtilisin/kexin type 9 (“PCSK9“) is an enzyme that has medical significance because it functions in cholesterol homeostasis. PCSK9 binds to a domain of the LDL receptor, inducing degradation. Reduced levels of the LDL receptor result in decreased metabolism of LDL, and thus increased LDL levels, a known risk factor for CVD.
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).
Residual Field is any field other than the ApoA-I Therapeutic Field.
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.
Statin a class of drugs that block cholesterol production in the body by inhibiting an enzyme called HMG-CoA reductase.
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.
Transferred IP Rights are any intellectual property rights that protect or otherwise cover the Transferred Technology, and without limitation includes the rights to the inventions covered by the patent applications listed in Schedule A of the Assignment and Services Agreement dated June 3, 2013 and effective May 1, 2012 and all divisionals, continuations, continuations-in-part or foreign counterparts of such patent applications and all patents issuing from such applications, divisionals, continuations, continuations-in-part or foreign counterparts, and all reissues, renewals, re-examination certificates and extensions of such patents or patent applications.
Transferred Technology is any technology conceived, invented or developed to the date of the Assignment and Services Agreement dated June 3, 2013 and effective May 1, 2012 that relates to pharmaceutical agents and methods for treating diseases and health conditions with a therapeutic agent that acts as a BET inhibitor (excluding compound RVX000222 (RVX-208) which increase the production ApoA-I protein used for the treatment of atherosclerosis), including without limitation, manufacturing processes or protocols, know-how, trade secrets, writings, documentation, data, technical information, techniques, results of experimentation and testing, diagnostic and prognostic assays, specifications, databases, any and all laboratory research, pharmacological, toxicological, analytical, quality control, pre-clinical and clinical data, and other information and materials, whether or not patentable.
Triglycerides a type of fat found in the blood and other parts of the body.
Type II Diabetes (see “Diabetes Mellitus”)
Valid Claim is a patent claim in a Licensed Patent (as extended by a Supplementary Protection Certificate, where applicable) that has not expired, where the claim has not been disclaimed or cancelled from the Licensed Patent.
Zenith is Zenith Epigenetics Corp., a corporation incorporated under the ABCA, which acquired RVX Therapeutics Inc. from the Company pursuant to a Plan of Arrangement completed on June 3, 2013.