1. Nourin®-dependent miRNAs are Novel Biomarkers for Acute Myocardial Ischemia

Medical Need: Patients with ischemic chest pain without necrosis, are difficult to diagnose in the Emergency Department (ED), and about 25% of positive troponin values are false positives due to non-specific myocardial injury in non-AMI patients with comorbidities. Thus, there is a need for biomarkers that are specifically highly expressed during acute myocardial ischemia, and not elevated with chronic diseases. To address this unmet need, Nour Heart has developed and patented the Nourin®-dependent miR-137 and miR-106b (N®miRs) as two disease-specific miRNA regulators that are linked to ACS pathology; one for myocardial ischemia (miR-137) and another for inflammation (miR-106b). Studies indicated that miRNAs play an important role in various critical biological processes and the dysfunctions of miRNAs are associated with a broad spectrum of diseases. An important advantage of miRNAs that they are expressed shortly after an ischemic event, earlier than protein.

Our Strategy: Dr. Salwa Elgebaly is the first to identify, patent, name, and register the tradename, Nourin® as a novel blood-based biomarker for the rapid detection of myocardial ischemia in absence of cell necrosis before it progresses to infarction. We have demonstrated that the ischemia/inflammation-dependent miR-137 and miR-106b are highly expressed in ACS patients with a half-life of 12 hours, but they were not found in non-ischemic control patients with comorbidities. N®miRs had sensitivity of >98% and specificity of >97% for classifying patients as ACS or non-ischemic control patients with comorbidities. Bioinformatics analysis confirmed the specificity of the ischemia-induced miR-137 in ACS by the absence of its upregulation in non-ischemic patients with chronic diseases.

Innovation: N®miRs are the first biomarkers to rapidly identify acute myocardial ischemia prior to necrosis, based on two disease-specific miRNA regulators linked to ACS pathology, and are not upregulated in non-ischemic patients with comorbidities. We also identified N®miR’s mechanism of molecular regulation as hypoxia-induced cell apoptosis/inflammation. Since high-sensitivity troponin (hs-Tn) was elevated in AMI, but not in UA patients, it supports the potential superiority of N®miRs over hs-Tn as novel acute ischemia-specific biomarkers elevated in UA patients. Clinically, N®miRs can be used to rapidly identify patients with acute myocardial ischemia in outpatient clinics (standard qPCR test) and emergency department (point-of -care assay).

Significance: The novel N®miR assay is a promising aid in the rapid and safe rule-out of the diagnosis of ACS in majority of symptomatic ED patients, which will potentially allow quick patient stratification. The novel Nourin® molecular diagnostic biomarkers can also rapidly identify a population of patients with ischemia, but without injury or infarction, thus, can improve treatment algorithms by allowing early initiation of crucial therapy while myocardial ischemia is still in the actionable state. This can minimize cardiac injury, improve patients’ outcomes and quality of life, reduce mortality, shorten hospital stays, and reduce healthcare costs.

2. Nourin®-dependent miRNAs are Beneficial for Women

Nourin®miRNAs: Novel Molecular Biomarkers for Early Identification or Exclusion of Myocardial Ischemia in Women Suspected of Having Coronary Artery Disease (CAD)

Heart disease is the number one cause of death worldwide, and women, at all ages, have higher disease mortality rates than that of men. Nour Heart’s blood-based biomarkers, Nourin protein and its regulatory miRNAs are elevated in the setting of myocardial ischemia before it progresses to infarction. Assessment of Nourin®miRNAs enables the rapid identification of a population of patients with ischemia, but without injury or infarction, and exclusion of myocardial ischemia, thus potentially improving the treatment algorithms for women.

Definition:

Myocardial ischemia is defined as reduction of blood flow to heart muscle (myocardium) due to a partial or complete blockage of one or more coronary arteries. Ischemic heart disease (IHD) is characterized by the presence of myocardial ischemia in patients with coronary artery disease (CAD), unstable angina (UA), acute myocardial infarction (AMI) (heart attack), and heart failure (HF).

Nourin®miRNAs:

Nour Heart, Inc. is the first to identify, patent, name, and register the tradename, Nourin®as a novel blood-based biomarker for the early detection of myocardial ischemia (in absence of cell necrosis) in cardiac patients, before progression to infarction. Nour Heart is developing Nourin miRNAs as novel blood biomarkers for early identification or exclusion of myocardial Ischemia in women suspected of having coronary artery disease.

Unmet Need for Women:

Heart disease is the number one cause of death worldwide, and women, at all ages, have higher disease mortality rates than that of men. Reasons for this include: 1) unlike men with “typical” symptoms, significant numbers of women frequently present with “questionable angina”; 2) cardiovascular imaging procedures are widely used to diagnose myocardial ischemia in patients suspected of having coronary artery disease (CAD), but are limited by lack of specificity and sensitivity, particularly in women, leading to incorrectly classifying a significant percentage of women as “low-risk”; and 3) absence of a blood-based biomarker that can detect myocardial ischemia earlier than cell death, may contribute to women being under-investigated and under-treated, with worse outcomes. In fact, many women are first diagnosed with CAD at the time of unstable angina, acute myocardial infarction (heart attack), or even heart failure (HF).

Nour Heart’s Strategy:

The company’s patented blood-based biomarkers, Nourin protein and its regulatory miRNAs are elevated in the setting of myocardial ischemia before it progresses to infarction. Nourin®biomarker has a strong negative predictive value enough to exclude and avoid further testing for myocardial ischemia, in the same way as NT-proBNP for heart failure and D-dimer for deep vein thrombosis. Ruling out myocardial ischemia in the majority of chest pain patients with the diagnosis of negative CAD will allow CAD-diagnosed chest pain patients to receive critical therapy, while they are still in the stable state prior to the development of irreversible damage (e.g., AMI and HF) or even death.

Advantages of Nourin®miRNAs Biomarkers:

As a non-invasive and less-expensive blood-based test, Nourin®miRNAs might be used as a routine screening test to rule out the majority of negative myocardial ischemia in chest pain patients (86%) and allow CAD-diagnosed patients (14%) to receive critical therapy, while they are still in the stable state. Initiating early therapy can potentially improve patients’ outcomes, quality of life, and saving lives, and reducing the high healthcare costs.