>>Metabasis Therapeutics Presents Results of Preclinical Studies for MB07811, Its Novel Product Candidate for the Treatment of Hyperlipidemia, at the Endocrine Society's Annual Meeting
Wednesday June 6, 9:00 am ET
SAN DIEGO--(BUSINESS WIRE)--Metabasis Therapeutics, Inc. (Nasdaq:MBRX - News), a biopharmaceutical company focused on the discovery, development and commercialization of novel drugs for the treatment of metabolic and liver diseases by applying unique capabilities for targeting the liver and liver pathways, announced today that two posters were presented at the Endocrine Society's 89th Annual Meeting in Toronto, Canada.
Both posters provide data on MB07811, the Company's liver-targeted, beta-subtype-selective thyroid hormone receptor (TR beta) agonist product candidate for the treatment of hyperlipidemia. The first poster provides data that show that MB07811 significantly reduced cholesterol and triglyceride levels in certain animal models with an improved therapeutic index as compared to the natural ligand, T3, or a prototype non-liver-targeted TR beta-selective agonist (KB-141). Oral administration of MB07811 to rats led to liver-selective tissue distribution with minimal effects on gene expression in extra-hepatic tissues. The studies in rats and mice showed an improved safety profile, including no cardiac effects and reduced effects on the thyroid hormone axis compared to KB-141.
The second poster provides data showing that oral administration of MB07811 resulted in a robust lowering of plasma cholesterol in a variety of animal models. Sustained efficacy was apparent with continued daily dosing for a duration of 4 to 9 weeks of treatment. Also noted, but not presented in the poster, were demonstrations of activity in a monkey model, and additive activity to statins in the monkey and rabbit models.
Thyroid hormone receptor (TR) agonists represent a novel and potentially important approach for reducing LDL-cholesterol (known as the "bad" cholesterol) and total cholesterol, liver and serum triglycerides, and lipoprotein (a) (Lp(a)). However, use of this approach has been hampered by dose-limiting cardiac effects as well as effects on the thyroid hormone axis, muscle metabolism and bone turnover. Metabasis believes that the combination of a TR beta-selective receptor agonist and liver-targeting could harness the efficacy of the approach by avoiding extra-hepatic activation of TR alpha receptors and TR beta receptors that may lead to these therapy-limiting side effects.
"MB07811 is the first of a novel class of product candidates discovered by Metabasis designed to lower serum cholesterol, serum triglycerides and liver fat," stated Dr. Mark Erion, executive vice president of research and development and chief scientific officer of Metabasis. "MB07811 combines a novel agonist selective for the beta isoform of the thyroid hormone receptor with our proprietary, liver-targeting HepDirect® prodrug technology. The combination of beta receptor selectivity, liver-targeting and other structural characteristics that limit extra-hepatic activity provides a product candidate that exhibits significant efficacy while avoiding side effects commonly associated with activation of thyroid hormone receptors outside the liver. If we can demonstrate these characteristics in humans, it should provide important evidence that MB07811 and this class of drugs could represent an exciting new therapeutic approach for treating hyperlipidemia."
Dr. Paul Laikind, president and chief executive officer of Metabasis, said, "The results of these studies and others supported the decision to initiate the clinical development of MB07811. The first human clinical study was successfully completed late last year and we expect to start a Phase 1b multiple dose study in healthy volunteers with moderately elevated LDL cholesterol by the end of this quarter."<<
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Waiting for the CS-917 results; clock ticking, supposed to be 2nd quarter.
Cheers, Tuck |
