Capstone Therapeutics (OTCQB:CAPS) (“the Company”) and its joint venture affiliate, LipimetiX Development, LLC (“JV”), announced today the initiation of dosing for its AEM-28 (Apo E mimetic peptide) Phase 1 human clinical trial in LDL/non-HDL cholesterol reduction.
The clinical study is a Phase 1a randomized, placebo-controlled, double-blinded, single center dose escalation study. The primary objectives are to evaluate safety and tolerability and to determine preliminary pharmacokinetics/pharmacodynamics of AEM-28 in normal healthy volunteers with elevated cholesterol. Approximately 36 subjects are planned for treatment at a hospital-affiliated clinical site in Perth, Australia.
Dennis Goldberg, PhD and President of LipimetiX, states “Apolipoprotein E (Apo E) has long been known to play a critical role in cholesterol and triglyceride metabolism. More recently, Apo E has been shown to provide unique protective effects to the artery wall. Scientists at the University of Alabama at Birmingham (UAB), led by Dr. G.M. Anantharamaiah, adroitly engineered AEM-28 as a small peptide that could be delivered therapeutically. Collaboratively, we have developed a significant body of preclinical work that establishes AEM-28 and its analogs as promising commercial candidates in reducing both cholesterol and, potentially, atherosclerotic lesions. We are delighted to now be moving this program into human clinical trials.”
The JV has a development plan to pursue regulatory approval of AEM-28 as treatment for Homozygous Familial Hypercholesterolemia (granted Orphan Drug Designation by FDA in 2012) and Severe Refractory Hypercholesterolemia. The initial development program will extend through Phase 1a and 1b/2a clinical trials and is expected to be completed in the fourth quarter of 2014.
Apolipoprotein E is a 299 amino acid protein that plays an important role in lipoprotein metabolism. AEM-28 is a 28 amino acid mimetic of Apo E that contains a domain that anchors into a lipoprotein surface while also providing the Apo E receptor binding domain, which allows clearance through the heparan sulfate proteoglycan (HSPG) receptors (Syndecan-1) in the liver. AEM-28, as an Apo E mimetic, has the potential to enhance the ability of atherogenic lipoproteins to be cleared from the plasma, completing the reverse cholesterol transport pathway, and thereby reducing cardiovascular risk. Since AEM-28 utilizes an alternative receptor for clearance by the liver, it may provide a therapeutic alternative for patients that lack a functional LDL receptor pathway (Homozygous Familial Hypercholesterolemia, HoFH), or have Severe Refractory Hypercholesterolemia. In addition, the potential artery wall protective effect may be highly beneficial to these patients and to others with atherosclerosis. The JV has an Exclusive License Agreement with The UAB Research Foundation for AEM-28 and certain of its analogs.