METABASIS THERAPEUTICS HEPDIRECT™ LIVER TARGETING PRODRUG TECHNOLOGY DESCRIBED IN THE JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
NATURE Highlights HepDirect™ in News and Views


SAN DIEGO, CA - June 25, 2004 -- Metabasis Therapeutics (NASDAQ: MBRX) announced today that the prestigious peer-reviewed journal, Journal of the American Chemical Society (JACS) published an article describing aspects of its proprietary HepDirect™ prodrug technology that the company uses to direct drugs to the liver to treat metabolic and liver diseases. Subsequent to the article appearing in JACS, Nature published a brief review highlighting the technology in its "News and Views" section.

The JACS article, "Design, Synthesis, and Characterization of a Series of Cytochrome P(450) 3A-Activated Prodrugs (HepDirect Prodrugs) Useful for Targeting Phosph(on)ate-Based Drugs to the Liver," (J. Am. Chem. Soc. 126, 5154-5163 (2004) describes the HepDirect™ prodrug technology and its applications for the liver-specific delivery of certain drugs. Liver specificity may provide a strategy for more effective therapy for chronic liver diseases and metabolic diseases linked to pathways in the liver. A prodrug is a biologically inactive derivative of a drug that undergoes chemical or enzymatic cleavage in the body to produce the drug. Typically, prodrugs break down throughout the body and therefore are not capable of organ-specific drug delivery. Results described in the article show that HepDirect prodrugs are capable of undergoing cleavage by a liver-specific enzyme resulting in delivery of high levels of the active form of a nucleoside to the liver. Nucleosides are a class of drugs known to treat certain viral infections and cancers and to regulate certain enzymes.

The periodical Nature (Nature Vol 429, May 6, 2004)., a leading science publication, highlighted the information published in the JACS article and provided a brief description of the benefits of the HepDirect™ prodrug technology in its "News and Views" section.

Two of the three product candidates that Metabasis is currently evaluating in human clinical trials use the HepDirect technology. Remofovir is a HepDirect prodrug of a proven antiviral agent which is being studied in patients as a treatment for hepatitis B. The second drug is MB07133, a HepDirect prodrug of an oncolytic agent. MB07133 is being studied in patients as a treatment for primary liver cancer, a deadly disease with few treatment options. In addition, Metabasis recently established a partnership with Merck to apply the HepDirect technology to certain compounds for the treatment of hepatitis C and is also using the technology on certain other internal projects for metabolic and liver diseases.

About Metabasis:
Metabasis Therapeutics, Inc. (www.mbasis.com) is a biopharmaceutical company focused on the discovery, development and commercialization of novel small molecule drugs principally to treat metabolic diseases linked to pathways in the liver and to treat liver diseases. The company has established a broad product pipeline targeting large markets with significant unmet medical needs. Metabasis currently has three internally discovered product candidates in clinical trials, CS-917, remofovir and MB07133 indicated for the treatment of type 2 diabetes, hepatitis B and primary liver cancer respectively.

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 Metabasis' HepDirect prodrug technology, its applications and capabilities, as well as statements about Metabasis' product candidates and research programs. 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; difficulties or delays in development, testing, obtaining regulatory approval, producing and marketing Metabasis' product candidates; adverse side effects or inadequate therapeutic efficacy of Metabasis' product candidates or proprietary technologies; Metabasis' dependence on collaborative partners; 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' prospectus filed with the Securities and Exchange Commission pursuant to Rule 424(b)(4) of the Securities Act on June 16, 2004. 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.