Posted on December 16th, 2014
by John Holliman
When we last spoke, Capstone Therapeutics and its joint venture with Lipimetix Development had just announced human clinical data from the first part of its Phase 1 cardiovascular drug study with AEM-28. We discussed having seen biomarker efficacy signals in non-HDL cholesterol, VLDL and Triglycerides (TG). So, why is that important? Unchecked high levels of VLDL and TGs contribute to heart attacks.
Non-HDL cholesterol is composed of Low Density Lipoprotein (LDL) and Very Low Density Lipiprotein (VLDL). These lipoproteins are a combination of proteins and lipids which allow fat and cholesterol to move around the body so they may be taken up by target cells. Cholesterol is a basic component of all cell membranes and is used by some tissues to make steroid hormones such as estrogen, testosterone and progesterone. Triglycerides or TGs are found in VLDL and chylomicron remnants in blood plasma. TGs play an important role in metabolism as energy sources while VLDL and chylomicron remnants serve as transporters of dietary fat.
When the amount of VLDL and TGs is properly regulated by the body’s natural systems, the vascular and metabolic systems are in sync and functioning well. However, problems develop when these lipoproteins and lipids get out of balance….often leading to severe cardiovascular disease. When in overabundance in blood plasma, these large, buoyant molecules are a primary contributor to atherosclerosis….or arterial plaque…which can unpredictably create an arterial occlusion and cause a heart attack. Over 1,000,000 people were hospitalized due to acute coronary syndrome in the US alone; another 400,000 people with heart attacks died before reaching the hospital!
The medical terms ”hypercholesterolemic”, “hyperlipidemic”, “hypertriglyceridemic” define populations who have too much cholesterol, lipid or triglyceride content in blood plasma. Although there are multiple causes, there exists a population that traces its cardiovascular disease to family genetics. Below you will find a chart that shows a number of rare disease or Orphan market indications that we believe can be served by AEM-28 and its analogs. Collectively, they represent large potential revenue markets and are substantially underserved by pharmaceutical competition.
Our lead target indication of Homozygous Familial Hypercholesterolemia (HoFH) was discussed in our October blog. Today, we’ll add another priority Orphan target in Acute Hypertriglyceridemic Pancreatitis. Occurring in approximately 6,000 hospitalized patients per year in the US, it is characterized by TG levels in excess of 1,000 mg/dL, severe abdominal pain and a mortality rate approaching 5%. Implying lengthy, expensive hospital stays, our thesis is that treatment with AEM-28 will lead to earlier release from the hospital at substantially lower cost than standard of care. In addition, it may take months to normalize TG levels after release from the hospital, which can lead to repeated episodes of pancreatitis with escalating morbidity and mortality.
Our drug, AEM-28 is showing itself to be a potent and rapid reducer of VLDL and TGs….up to 76% and 74%, respectively, reduction from baseline in an hour in human clinical trials. As a result, we are following the data as it leads to potential utility in new, unmet medical conditions. Continued favorable study results could ultimately deliver positive therapeutic outcomes to these rare lipid disorders.
Capstone Therapeutics Corp.
Forward Looking Statements
Statements in this blog post or otherwise attributable to Capstone regarding our business that are not historical facts are forward looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These forward-looking statements involve risks and uncertainties that could cause actual results to differ materially from predicted results. These risks include the factors discussed in our Form 10-K for the fiscal year ended December 31, 2014, and other documents we file with the U.S. Securities and Exchange Commission.