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Metabasis Therapeutics Announces the First Publication on MB07811, Its Novel Product Candidate for the Treatment of Hyperlipidemia, in the Proceedings of the National Academy of Sciences

SAN DIEGO--(BUSINESS WIRE)--Sep 19, 2007 - Metabasis Therapeutics, Inc. (Nasdaq:MBRX) announced today that an article describing the potential benefits of its product candidate for hyperlipidemia, MB07811, was published in the Proceedings of the National Academy of Sciences (PNAS), Vol. 104, Issue No. 39, pp. 15490 - 15495. The article, by Dr. Mark Erion et al., is entitled "Targeting Thyroid Hormone Receptor-Beta Agonists to the Liver Reduces Cholesterol and Triglycerides and Improves the Therapeutic Index".

The publication highlights the discovery of MB07811, the Company's liver-targeted, beta-subtype-selective thyroid hormone receptor (TR-beta) agonist product candidate for the treatment of hyperlipidemia that is currently being evaluated in a clinical trial. The article also provides results from preclinical studies in rats and mice. The studies showed that in rodent models, MB07811 significantly lowered LDL-cholesterol (the "bad" cholesterol) and plasma triglyceride levels as well as liver fat, with an acceptable safety profile and an improved therapeutic index as compared to non liver-targeted TR agonists, T3 and KB-141. More specifically, MB07811-treated animals exhibited lower lipid levels at doses that showed no significant changes in heart rate, cardiac function, heart weight or body weight, glycemia or thyroid stimulating hormone levels.

It has long been known that thyroid hormone receptor activation plays a role in controlling lipid levels in the body. Efforts to harness the therapeutic potential of thyroid hormone receptor (TR) agonists for the treatment of hyperlipidemia or obesity have been underway for decades, but the approach remains largely unexplored in humans due to dose-limiting cardiac effects as well as effects on the thyroid hormone axis, muscle metabolism and bone loss. Metabasis believes that the combination of a TR-beta-selective receptor agonist and liver-targeting could avoid extra-hepatic activation of thyroid hormone receptors that may lead to these therapy-limiting side effects. The publication provides evidence for this liver targeting capability.

"We are very excited to have our first major publication on MB07811 accepted by such a prestigious journal as PNAS," stated Dr. Paul Laikind, president and chief executive officer of Metabasis. "Harnessing the beneficial therapeutic effects of thyroid hormone receptor activation, while avoiding the detrimental side effects, has long been a goal of the pharmaceutical industry. Our liver-targeted TR agonists represent a novel and potentially important new approach for realizing this goal."

"MB07811 has been evaluated in multiple studies in animals ranging from rodents to primates with encouraging results. We have demonstrated a unique profile that combines reduction of LDL-cholesterol and total cholesterol with reduced serum triglycerides, lipoprotein (a) and liver fat. In addition, we have also presented data that suggests that this approach could provide an added benefit when used with statins. These various attributes, should they be verified in human clinical trails, could give this product candidate an important place in the large and growing market for treatments used to prevent cardiovascular disease," concluded Dr. Laikind.

The Company successfully completed a Phase 1a clinical trial for MB07811 at the end of 2006, which provided evidence that the candidate is safe and well-tolerated when administered as a single dose. MB07811 is currently being studied in a Phase 1b multiple dose clinical trial, which is expected to be completed in the fourth quarter of 2007. This 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 (

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(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 potential benefits of, and market for, MB07811, as well as the results of the pending Phase 1b clinical trial 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.


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

Posted: September 2007