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Metabasis Presents Preclinical Results for MB07803, Its Product Candidate for Type 2 Diabetes, and Its Glucagon Antagonist Program at the American Diabetes Association Meeting

SAN DIEGO--(BUSINESS WIRE)--June 10, 2008 - Metabasis Therapeutics (Nasdaq:MBRX) announced today that Dr. Paul van Poelje gave an oral presentation and presented a poster during the 68th Scientific Sessions of the American Diabetes Association (ADA). The oral presentation, entitled, "MB07803, a Prodrug of a Second Generation Fructose-1,6-Bisphosphatase Inhibitor, Lowers Blood Glucose in Diabetic Rodents and Cynomolgus Monkeys," highlighted preclinical data for MB07803, the Company's product candidate for the treatment of type 2 diabetes. The poster presented during ADA, entitled, "Glucagon Action is a Major Determinant of Hyperglycemia in the Fasted, Fed and Postprandial States of Animal Models of Type 2 Diabetes," summarized preclinical data demonstrating the therapeutic potential of a novel class of glucagon receptor antagonists to treat type 2 diabetes.

Dr. van Poelje's oral presentation described the preclinical profile for MB07803, a product candidate designed to improve upon the pharmacokinetic profile of the Company's first generation fructose-1,6-bisphosphatase (FBPase) inhibitor, CS-917. MB07803 was shown to have excellent pharmacokinetic properties in monkeys, characterized by high oral bioavailability and an extended half-life. In a fasted monkey model, MB07803 effectively lowered blood glucose without altering circulating lactate or triglyceride levels. The potency of MB07803 in this model was estimated to be 10-fold greater than that of CS-917. MB07803 was also shown to be a potent inhibitor of gluconeogenesis in human hepatocytes and to markedly lower blood glucose in a diabetic rodent model after a single dose and during multiple weeks of treatment.

MB07803 regulates excess glucose production in the liver by inhibiting FBPase, an enzyme that catalyzes a key step in the gluconeogenesis pathway. Excess hepatic glucose production via gluconeogenesis is a major contributing factor to the elevated glucose levels associated with increased morbidity and mortality in patients with type 2 diabetes. MB07803 met its primary efficacy endpoint in a recent phase 2a clinical trial completed by Metabasis. In this clinical trial, a statistically and clinically significant reduction in fasting plasma glucose (FPG) at day 28 versus placebo (p=0.0177) was observed when MB07803 was administered at 200 mg.

The poster presented at ADA described data from several preclinical studies for Metabasis' glucagon receptor antagonist program, suggesting that the compound class has the potential to provide an important new therapy for type 2 diabetes. Hyperglycemia in patients with type 2 diabetes is believed to result in part from inappropriately elevated levels of plasma glucagon, which cause the liver to overproduce glucose. Glucagon antagonists are designed to interfere with the binding of glucagon to its receptor, thereby reducing glucose production by the liver.

As illustrated in the poster, one of the Company's lead glucagon receptor antagonists potently inhibits glucagon-stimulated glucose production by human hepatocytes, as well as lowers fasting and postprandial blood glucose and improves oral glucose tolerance in four common rodent models of type 2 diabetes. In addition, the lead glucagon receptor antagonist was shown to have favorable pharmacokinetic properties in rats. Metabasis expects to recommend a compound from its glucagon receptor antagonist program for clinical development later in the year.

"Over the last several years, Metabasis has focused its R&D efforts on metabolic diseases," commented Dr. Mark Erion, executive vice president of research and development and chief scientific officer. "The Company's presentations at ADA highlight two of the several programs we have that target type 2 diabetes, which is one of the most widespread and costly diseases worldwide. MB07803 is our second generation FBPase inhibitor that successfully completed a Phase 2a clinical trial earlier this year, in which it was safe and well-tolerated and produced a statistically and clinically meaningful decrease in FPG. While it is relatively early in its development, the results suggest that MB07803 may have the potential to achieve efficacy in line with current marketed therapies for type 2 diabetes.

"We are also very excited about the prospects of our glucagon receptor antagonist program. The glucagon receptor is a well validated target that has been pursued by the pharmaceutical industry for at least two decades. We feel that glucagon receptor antagonists have the potential to provide significant therapeutic benefit to patients with type 2 diabetes. We look forward to recommending a lead candidate for clinical development later in 2008."

About Type 2 Diabetes:

Diabetes is a rapidly growing, worldwide health crisis. According to the International Diabetes Federation, in 2007, the number of patients suffering with diabetes worldwide reached over 245 million, with treatment and prevention costs reaching approximately $232 billion. Approximately 90% of patients with diabetes worldwide have type 2 diabetes. According to the American Diabetes Association, diabetes is the fastest growing disease in the U.S. In 2007, approximately 20 million Americans, or 7% of the U.S. population, were afflicted with diabetes, with costs associated with the disease reaching $174 billion.

About Metabasis (

Metabasis is a biopharmaceutical company using its proprietary technologies, scientific expertise and unique capabilities for targeting the liver and liver pathways. The Company has established a broad pipeline of product candidates and advanced research programs targeting large markets with significant unmet needs. Metabasis' core area of focus is on the discovery and development of drug candidates to treat metabolic diseases such as hyperlipidemia and diabetes, among others. Although not a core focus of the Company, Metabasis has also discovered and developed drug candidates indicated for the treatment of liver diseases such as hepatitis and primary liver cancer, which it now intends to license or partner. All product candidates were developed internally using proprietary technologies.

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 efficacy and benefits of, and the potential market for, MB07803; and the progress and prospects of Metabasis' glucagon receptor antagonist program, including the expected recommendation of a compound from that program for clinical development. 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, risks and uncertainties related to the progress and timing of clinical trials for Metabasis' product candidates; the fact that positive results from preclinical studies and early clinical trials does not necessarily mean later clinical trials will succeed; difficulties or delays in development, testing, obtaining regulatory approval, producing and marketing Metabasis' product candidates; serious adverse side effects or inadequate efficacy of, or serious adverse events related to, Metabasis' product candidates or proprietary technologies; the risk that Metabasis will not be able to build more value or retain rights for direct commercialization of its product candidates; Metabasis' dependence on its licensees and collaborators for the clinical development and registration of, as well as information relating to, certain of its product candidates; potential conflicts with collaborators that could delay or prevent the development or commercialization of Metabasis' product candidates; the scope and validity of intellectual property protection for Metabasis' product candidates, proprietary technologies and their uses; competition from other pharmaceutical or biotechnology companies; Metabasis' ability to obtain additional financing to support its operations; and other factors discussed in the "Risk Factors" section of Metabasis' Quarterly Report on Form 10- Q for the three months ended March 31, 2008 and in Metabasis' other filings with the Securities and Exchange Commission. 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

Posted: June 2008