05.11.2007 14:00:00

Metabasis Presents Preclinical Results at AASLD Showing MB07811, Its Novel Product Candidate for the Treatment of Hyperlipidemia, Reduces Liver Fat

Metabasis Therapeutics, Inc. (Nasdaq:MBRX) announced that a poster was presented today at the 58th Annual Meeting of the American Association for the Study of Liver Diseases in Boston, MA. The poster, which was selected as a Presidential Poster of Distinction, placing it in the top 10% of those selected for presentation, provides data from a preclinical study for MB07811, the Company’s clinical-stage liver-targeted beta-subtype-selective thyroid hormone receptor (TRß) agonist product candidate for the treatment of hyperlipidemia. The poster presents data demonstrating that oral administration of MB07811 to three commonly used animal models of diabetes and obesity, for two to nine weeks, resulted in marked reduction in liver fat (hepatic steatosis). Fatty liver is a common condition, which is associated with insulin resistance and an increased risk of cirrhosis and liver failure. MB07811 reduced hepatic fat content in all animal models tested while T3, the natural TR ligand, failed to reduce hepatic fat content in two of the three models. Additionally, MB07811 increased the expression of fat-burning genes in the liver at doses that were previously shown to be devoid of effects on TR-sensitive gene expression in peripheral tissues. The ability to selectively activate TR-sensitive genes in the liver is attributed to the liver targeting properties of MB07811. The efficacy of MB07811 has been studied extensively in preclinical models across species ranging from rodents to primates with very encouraging results. For instance, in other preclinical studies in rodents, results indicate that targeting TR agonists to the liver has the potential to lower both LDL-cholesterol (the "bad” cholesterol) and liver and serum triglycerides levels with an acceptable safety profile and an improved therapeutic index as compared to non-liver-targeted TR agonists. MB07811 has also shown efficacy equivalent to, and additive with, the widely used statin atorvastatin (Lipitor®) in certain rabbit and primate models. MB07811 was shown to be safe and well-tolerated in a Phase 1a clinical trial when administered as a single dose and the product candidate is currently being studied in a Phase 1b multiple dose clinical trial. "The findings presented today suggest that MB07811, which is currently being clinically evaluated as a new approach for the treatment of hyperlipidemia, may potentially offer the added benefit of reducing liver fat content,” commented Dr. Mark Erion, executive vice president, research and development and chief scientific officer. "The reduction of liver fat content following oral-administration of MB07811 results from targeting the TR agonist to the liver, which unlike T3, leads to increased fat metabolism in the liver without simultaneous production of fat precursors from peripheral tissues. The ability of MB07811 to reduce liver fat content, coupled with its ability to lower plasma cholesterol and triglyceride levels and levels of atherogenic lipoproteins such as LDL and Lp(a), suggest that MB07811 could have a unique and differentiated profile compared to other therapies either currently on the market or in the clinic for the treatment of hyperlipidemia.” About Metabasis (www.mbasis.com): Metabasis Therapeutics is a biopharmaceutical company focused on the discovery, development and commercialization of novel drugs to address some of the world’s most widespread and costly chronic diseases. The Company has established a pipeline that includes clinical stage and preclinical product candidates targeting major diseases with significant unmet medical needs. Targeted diseases include metabolic diseases such as diabetes, hyperlipidemia and obesity as well as liver diseases such as hepatitis and primary liver cancer. Metabasis has developed several proprietary technologies for use in discovering and optimizing drugs, including the NuMimetic™ and HepDirect® technologies. Metabasis is continuing to identify and develop new product candidates using its proprietary technologies and expertise. Forward-Looking Statements: Statements in this press release that are not strictly historical in nature constitute "forward-looking statements.” Such statements include, but are not limited to, references to the pre-clinical and clinical trial results, potential safety and efficacy and further development of MB07811. Such forward-looking statements involve known and unknown risks, uncertainties and other factors which may cause Metabasis’ actual results to be materially different from historical results or from any results expressed or implied by such forward-looking statements. These factors include, but are not limited to, the progress and timing of clinical trials for Metabasis’ product candidates; the fact that positive results from clinical trials does not necessarily mean later clinical trials will succeed; serious adverse side effects of, or serious adverse events related to, Metabasis’ product candidates or proprietary technologies; difficulties or delays in development, testing, obtaining regulatory approval, producing and marketing Metabasis’ product candidates; the potential and progress of preclinical compounds and programs; and other factors discussed in the "Risk Factors” section of Metabasis’ Quarterly Report on Form 10-Q for the quarter ended June 30, 2007. All forward-looking statements are qualified in their entirety by this cautionary statement. Metabasis is providing this information as of this date of this release and does not undertake any obligation to update any forward-looking statements contained in this release as a result of new information, future events or otherwise.
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