Mar 27 2015
Tekmira Pharmaceuticals Corporation an industry-leading therapeutic solutions company focused on developing a cure for chronic hepatitis B virus infection (HBV), announced today that new preclinical data on TKM-HTG, an RNAi therapeutic, were presented at the Keystone Symposia Conference: Liver Metabolism and Nonalchoholic Fatty Liver Diseases, in Whistler, Canada, March 22-27, 2015. Dr. Narayanan Hariharan, Senior Director of Research for Tekmira, delivered a podium presentation at the conference titled, "Novel RNAi-Lipid Nanoparticle Therapeutics for Hypertriglyceridemia," and a poster presentation titled, "TKM-ApoC3, an RNAi-Lipid Nanoparticle Therapeutic, Ameliorates Hypertriglyceridemia and Improves Metabolic Profile in Human-ApoC3 Transgenic Mice."
TKM-HTG is a product candidate in Tekmira's non-HBV product pipeline for the treatment of hypertriglyceridemia (HTG). TKM-HTG is being developed as a dual component RNAi therapeutic that simultaneously targets two important genes expressed in the liver, which are known to play a significant and complementary role in triglyceride metabolism. The most important finding obtained in the pre-clinical studies are the super-additive effects on plasma triglycerides by silencing the Apolipoprotein C3 (ApoC3) and Angiopoietin like protein 3 (ANGPTL3) genes, which are expressed in the liver, in a well validated model of HTG. High triglyceride levels are medically linked to an increased risk of cardiovascular disease, fatty liver disease, insulin resistance and pancreatitis.
"Today, Dr. Narayanan Hariharan presented exciting pre-clinical data demonstrating a unique mechanism of action of our TKM-HTG agent which reflects the value, we believe, resides in our non-HBV assets. Our aim is to achieve rapid and sustained reductions of triglycerides and address the limitations of existing HTG treatments with TKM-HTG," said Dr. Mark J. Murray, Tekmira's President and CEO. "We are encouraged by the results presented and we are advancing TKM-HTG into investigational new drug application-enabling studies."
Key summary points from Dr. Hariharan's presentation include:
- Preclinical studies employed two well validated models of HTG including human ApoC3 transgenic (Tg) mouse model and high-fat containing diet fed mouse model. In the human ApoC3-Tg mouse model, silencing of ApoC3 gene was accomplished, which resulted in rapid, potent and sustained plasma triglyceride (TG) lowering, with the lowest effective dose at 0.03 mg/kg. Duration of gene silencing and TG lowering effects from a single administration of the ApoC3 RNAi trigger lasted for more than 2 weeks.
- In addition, beneficial cholesterol profile changes and significant glucose lowering effects were also observed.
- In the high-fat containing diet fed mouse model, silencing of both the ApoC3 and ANGPTL3, genes, resulted in super-additive plasma triglycerides lowering effects. Doses of 0.125 mg/kg + 0.125 mg/kg in combination were superior to either 0.25 mg/kg or 0.5 mg/kg for the individual RNAi-triggers. This demonstrates the advantage of using a dual-component RNAi-therapeutic for the potential treatment of HTG.
Source: http://www.tekmira.com/