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Our Science

Precision Medicine

Pharmacogenetics for cardiovascular diseases

Precision Medicine refers to the tailoring of medical treatment to the individual characteristics of each patient through the ability to classify individuals into subpopulations that differ in their susceptibility to a particular disease, in the biology and/or prognosis of those diseases they may develop, or in their response to a specific treatment. Pharmacogenetics is the study of inherited genetic differences in drug metabolic pathways which can affect individual responses to drugs, both in terms of therapeutic effect as well as adverse effects.

Our Science

Precision Medicine

Pharmacogenetics for cardiovascular diseases

Precision Medicine refers to the tailoring of medical treatment to the individual characteristics of each patient through the ability to classify individuals into subpopulations that differ in their susceptibility to a particular disease, in the biology and/or prognosis of those diseases they may develop, or in their response to a specific treatment. Pharmacogenetics is the study of inherited genetic differences in drug metabolic pathways which can affect individual responses to drugs, both in terms of therapeutic effect as well as adverse effects.

Cardiovascular Disease and Atrial Fibrillation

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Cardiovascular disease generally refers to conditions that involve narrowed or blocked blood vessels that can lead to a heart attack, chest pain (angina) or stroke. Diseases under the cardiovascular disease umbrella include blood vessel diseases, such as coronary artery disease; heart rhythm problems (arrhythmias); and heart defects you’re born with (congenital heart defects), among others.

Atrial fibrillation (AF, or A-fib) is a disorder in which the normally regular and coordinated contraction pattern of the heart’s two small upper chambers, or the atria, becomes irregular and uncoordinated. The irregular contraction pattern associated with AF causes blood to pool…

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Gencaro™

An Unmet Need

Our lead product candidate, Gencaro™ (bucindolol hydrochloride), is a pharmacologically unique beta-blocker and mild vasodilator that we are evaluating in a clinical trial for the treatment of atrial fibrillation, or AF, in patients with heart failure with reduced left ventricular ejection fraction, or HFREF.

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Beta-blockers, a well characterized class of drugs, target cardiac myocytes to reduce adverse beta1- adrenergic signaling that causes cardiac chamber remodeling. We believe Gencaro’s mechanism of action (MOA) is unique among beta-blockers due to its sympatholytic (norepinephrine lowering) and inverse agonism (inactivation of constitutively active receptors) properties.

We have identified common genetic variations in receptors in the cardiovascular system that we believe interact with Gencaro’s pharmacology and may predict patient response to the drug. The genotype which responds most favorably to Gencaro, beta-1 389 arginine homozygous, is present in approximately 50% of the U.S. population.

The approved therapies for the treatment or prevention AF have certain disadvantages in heart failure patients, such as toxic or cardiovascular adverse effects, and most of the approved drugs for AF are contraindicated or have warnings in their prescribing information for such patients. We believe there is an unmet medical need for new AF treatments that have fewer side effects than currently available therapies and are more effective, particularly in heart failure patients.

Gencaro™ Heart Failure Development Program Summary

Gencaro™ has been studied in seven clinical trials in HFREF patients and 1 clinical trial in myocardial infarction (MI) patients, comprising over 3,000 patients. Gencaro™ is currently being evaluated in the GENETIC-AF clinical trial as a potential treatment for atrial fibrillation in HFREF patients.