ALT-2074 is small molecule organoselenium compound which acts as a glutathione peroxidase mimetic. This enzyme is one of the key enzymes known to be involved in prevention of lipid peroxidation and serves as one of the body’s key antioxidant mechanisms to limit damage from free radicals and reactive oxygen species (ROS). The compound has been shown to be particularly effective in limiting myocardial damage in preclinical studies in animals transgenically engineered with a common haptoglobin variant which exists in about 40% of the human population. Haptoglobin is a protein in the blood which scavenges free hemoglobin, a reactive molecule from circulation. Diabetic individuals with this variant form (Hp 2-2) of haptoglobin are at elevated risk for significant cardiovascular complications and death following a myocardial infarction. In a preclinical study with mice transgenically engineered with the Hp 2-2 protein, ALT-2074 significantly reduced the extent of myocardial damage subsequent to an ischemia-reperfusion event which mimics the natural course of events following loss of blood flow to the myocardium. When compared to placebo controls, ALT-2074 reduced myocardial damage by greater than 80%.

ALT-2074 is under current clinical investigation for the potential to reduce clinical damage secondary to a percutaneous coronary intervention (PCI) in which a balloon occlusion to the coronary artery is used to compress atherosclerotic plaque prior to stent placement. This balloon occlusion induces a small amount of damage to the myocardium served by this vessel secondary to the ischemia-reperfusion cascade. Serial measurement of two key cardiac protein markers will serve as indices of a cardioprotective effective effect of ALT-2074. All of the patients in this study are diabetics who have acute coronary syndrome or angina requiring angioplasty.

A future trial of this compound will evaluate the effects of the compound in diabetic patients with the Hp 2-2 phenotype and will assess several key inflammatory, collagen, and markers of lipid peroxidation.

The company has licensed technology that identifies methods for the analytical determination of the variant haptoglobin forms. Prior human use of this compound by another company indicated that the compound was beneficial in inflammatory bowel disease. The company has developed an extensive intellectual property portfolio based on the haptoglobin genotyping, and use of ALT-2074 and related compounds. These are predicted to be of value in a pharmacogenomically targeted population of diabetic individuals with the Hp 2-2 genotype.

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