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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

SAN DIEGO--(BUSINESS WIRE)--Jun 6, 2007 - Metabasis Therapeutics, Inc. (Nasdaq:MBRX), 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-li miting 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(R) 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."

About Metabasis (

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 an d costly chronic diseases. By applying our proprietary technologies and scientific expertise, including unique capabilities for targeting the liver and liver pathways, the Company has established a pipeline that includes preclinical and clinical product candidates targeting 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(TM) and HepDirect(R) 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 development for Metabasis' product candidates; the fact that positive results obtained during early development do not necessarily mean later development 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 pre-clinical compounds and programs; and other factors discussed in the "Risk Factors" section of Metabasis' Quarterly Report on Form 10-Q for the year ended March 31, 2007 . All forward-looking statements are qualified in their entirety by this cautionary statement. Metabasis is providing this information as of the 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.


Metabasis Therapeutics, Inc.
Constance Bienfait
Vice President
Investor Relations & Corporate Communications
(858) 622-5575


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