KineMed Inc. (www.kinemed.com) today announced its successful award of a Rapid Access to Intervention Development (RAID) peer-reviewed grant by the National Institute of Health to advance an HDL mimetic, designated FX-5A, designed to reverse atherosclerosis and heart disease.
Reverse cholesterol transport is the body’s natural process for removing unwanted cholesterol from sites of excessive deposition, including atherosclerotic plaques in arterial walls. Reversing atherosclerosis, the deposit of plaques containing cholesterol and lipoid material in arteries, by increasing the number of high-density lipoprotein, “HDL”, particles and increasing reverse cholesterol transport, represents a new therapeutic paradigm. Current low-density lipoprotein, “LDL” cholesterol, lowering therapies are effective to reduce the risk of coronary events by only 30%, whereas studies suggest that for any given level of LDL-cholesterol, cardiovascular risk may be further reduced by an increase in HDL particle levels.
“We are honored to acknowledge this substantial award from the NIH BrIDGs program for assistance with manufacturing, formulation and IND enabling safety studies, to advance our novel ApoA-I mimetic lead compound for the treatment of atherosclerosis and cardiovascular diseases,” said Dr. Scott Turner, Executive Vice-President, R&D at KineMed. “Raising HDL particle levels with the goal of increasing reverse cholesterol transport is a prime objective of our approach for further reduction of coronary events in patients at risk. While there are many current therapies in development looking to mimic human HDL, FX-5A has strong potential as a game-changing therapeutic because it is a small synthetic peptide optimized to efflux cholesterol, whereas the majority of other strategies focus on biologics.”
“We thank the NIH and are proud to be collaborating on progress towards a life-saving therapy that can potentially bring benefit to millions of Americans threatened by cardiovascular disease. This award highlights KineMed’s powerful insights into cholesterol biology and our ability to more rapidly and cost-efficiently advance therapeutics,” said David Fineman, CEO & President of KineMed. “That we are able to see the mechanism of action – in action – is key. Through quantitative assays that we have developed and validated in association with thought leaders in this field, we can not only measure cholesterol efflux, but also account for the pluripotency of drug effects, by seeing both on- and off-target effects. These same techniques enable us to subtype the relevant patient populations that can be effectively treated, towards the broader goals of personalized medicine to streamline societal healthcare costs to large populations.”
About HDL Therapy
Intravenous administration of apolipoprotein (apo) A-I complexed with phospholipid has been shown to rapidly reduce plaque size in both animal models and humans. Short synthetic amphipathic peptides can mimic the antiatherogenic properties of apoA-I and have been proposed as alternative therapeutic agents. High-density lipoprotein (HDL) levels have consistently been shown to be inversely related to cardiovascular disease risk. HDL promotes the flux of excess cholesterol from peripheral cells to the liver by the reverse cholesterol transport (RCT) pathway. Based on the inverse relationship between HDL and the incidence of cardiovascular disease, there has been great interest in developing drugs that raise HDL. Except for niacin there has been limited success in finding small-molecule drugs that increase HDL and decrease cardiovascular disease. This has prompted the development of a new treatment strategy called HDL therapy, which involves the intravenous infusion of exogenous HDL to rapidly stabilize patients with acute coronary syndrome. Even a single infusion of HDL has been shown in animal studies to reduce plaque size, lipid content, and inflammation. In human clinical trials, benefit in reducing atherosclerotic plaques has been observed after only 4-5 treatments with HDL therapy, and hence it has been proposed as a way to rapidly stabilize acute coronary syndrome patients.
Statin drugs are currently the predominant class of drugs prescribed to reduce the synthesis of LDL-cholesterol in the body. As a complement to statins, HDL therapy can move a large amount of cholesterol out of the body, up to 10g per day -- about the size of a pat of butter.
The FX-5A peptide is a bihelical peptide, where substituting five nonpolar amino acids on the hydrophobic face of the helix with alanine, hence its name, reduced the lipid affinity of the second helix. This arrangement of helices was found to reduce its cytotoxicity and increase its specificity for removing cholesterol from cells. Intravenous administration of the 5A peptide complexed with phospholipid was found in apoE-KO mice to raise HDL, promote RCT, and reduce atherosclerosis, indicating that 5A shares many of the same beneficial antiatherogenic features of apoA-I and may be a suitable substitute for apoA-I in HDL therapy. KM has rights to commercialize FX-5A.
About Cardiovascular Disease and Atherosclerosis
Cardiovascular disease is an increasingly challenging global healthcare problem and in the United States affects over one quarter of Americans over the age of 65. Hardening of the arteries, also called atherosclerosis, is a common disorder. It occurs when fat, cholesterol, and other substances build up in the walls of arteries and form hard structures called plaques. Over time, these plaques can block the arteries and cause symptoms and problems throughout the body.
About KineMed, Inc.
KineMed, based in California, is a world-leading specialist in the identification and measurement of the biochemical processes that cause disease. KineMed’s deep biological expertise combined with its core, patented, Dynamic Proteomics technology platform, accelerates and lowers the cost of diagnostic and therapeutic R&D.
KineMed is constantly seeking to expand its portfolio of collaborations with pharmaceutical, CRO, histopathology, diagnostics, medical instruments and biotechnology partners. Established programs with premier pharmaceutical collaborators address critical challenges facing drug discovery:
Last updated on: 10/04/2012