Metabasis Therapeutics Presents Preclinical Results Demonstrating Potential Advantages of MB07811 as a Treatment for Hyperlipidemia

SAN DIEGO--(BUSINESS WIRE)--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 targeting the liver and liver pathways, announced that yesterday it presented results from a preclinical study with MB07811 at the 234^th National Meeting of the American Chemical Society in Boston, MA.

“MB07811 is the first of a novel class of thyroid hormone receptor agonists discovered by Metabasis that are designed to safely lower serum cholesterol and triglycerides”

The presentation provided data on MB07811, the Company’s liver-targeted, beta-subtype-selective thyroid hormone receptor (TRβ) agonist product candidate that is currently being evaluated in a clinical trial as a treatment for hyperlipidemia. The results presented provided evidence that in normal rats, MB07811 significantly reduced serum cholesterol at doses devoid of effects on the heart and the thyroid hormone axis. Results in a cholesterol-fed rat model were also presented that provided further evidence of the advantages of using Metabasis’ proprietary liver targeting approach. In this animal model, MB07811 treatment resulted in significant cholesterol lowering with little to no effect on other tissues as compared to non-liver targeted TR and TRβ agonists.

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. Targeting a TRβ agonist to the liver is designed to result in efficacy while avoiding these well known potential side effects of TRβ agonists.

“MB07811 is the first of a novel class of thyroid hormone receptor agonists discovered by Metabasis that are designed to safely lower serum cholesterol and triglycerides,” said Dr. Mark Erion, executive vice president of research and development and chief scientific officer. “We are excited about this new approach. Targeting TRβ agonists to the liver has the potential to achieve the desired effects on cholesterol with an acceptable safety profile. Moreover, our preclinical studies have suggested that in addition to lowering cholesterol and triglycerides, these agents could have the added benefit of reducing lipoprotein (a) and liver fat, risk factors that have been linked to cardiovascular and other diseases. This profile combined with a wide therapeutic index could make this an important new class of drugs.”

The Company successfully completed a Phase 1a clinical trial with MB07811 at the end of 2006, in which the candidate was shown to be safe and well-tolerated when administered as a single dose. MB07811 is currently being studied in a Phase 1b multiple dose clinical trial expected to be completed in the fourth quarter of 2007. The current clinical trial is a 14-day, rising dose trial in healthy volunteers with modestly elevated LDL-cholesterol levels. The clinical trial will evaluate the safety and tolerability of MB07811 in approximately 30-40 patients, and could potentially provide preliminary evidence of cholesterol-lowering activity and evidence of an improvement of the therapeutic index, a key property that the liver-targeting is designed to address.

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, statements regarding the advantages of Metabasis' proprietary liver-targeting approach and the preclinical and clinical results, safety and potential efficacy 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.