METABASIS THERAPEUTICS, INC. ANNOUNCES THE COMMENCEMENT OF CLINICAL TESTING OF HEPAVIR B IN PATIENTS WITH HEPATITIS B

SAN DIEGO, CA - April 3, 2003 -- Metabasis Therapeutics, Inc. (Metabasis) announced today that Ribapharm, Inc, (Ribapharm) has begun clinical testing of Hepavir B, an orally active, liver-specific prodrug of the proven antiviral agent adefovir. Hepavir B was developed by Metabasis and licensed to Ribapharm in October 2001. Ribapharm filed an IND in October 2002, which was subsequently allowed by the United States Food and Drug Administration.

Hepavir B was developed using Metabasis proprietary HepDirect™ Technology, a broadly applicable prodrug technology that results in the production of the active drug specifically in the liver. By enabling higher drug concentrations in the liver and minimizing exposure to non-liver tissues, HepDirect prodrugs may improve efficacy, reduce toxicity and thus improve the treatment of liver and liver-related diseases. Adefovir, the active ingredient of Hepavir B, has proven to be an effective drug for the treatment of patients with chronic hepatitis B. However, studies have shown that accumulation of the drug in the kidney results in dose limiting renal toxicity. The HepDirect Technology is designed to change the biodistribution of the active form of adefovir and thereby result in an improved therapy. Preclinical studies show that the HepDirect prodrug of adefovir, Hepavir B, achieves significantly higher levels of the active form in the liver and lower levels in the kidney resulting in an overall 10- to 50-fold increase in liver targeting. Metabasis believes that this redistribution of the drug will allow for more optimal dosing and therefore a more efficacious drug with improved safety.

Dr. Paul Laikind, Chairman, President and CEO of Metabasis stated, "We are very pleased with the progress made in the development of Hepavir B. Ribapharm previously announced that it had successfully completed a Phase 1 trial with the drug.. This was important both for the continued development of Hepavir B but also because it marked the first clinical experience with our liver-specific prodrug technology, HepDirect. The recent initiation of studies in patients infected with the hepatitis B virus marks another important milestone in the development of the drug.

Dr. Mark Erion, Executive Vice President of Research and Development said, "The success to date with Hepavir B further demonstrates the potential of the HepDirect Technology for developing new and improved drugs for the treatment of liver and liver-related diseases. Based on the preclinical experience, the high liver specificity provided by the HepDirect Technology should minimize systemic exposure and lead to an overall improvement in the therapeutic index of the drug. The second HepDirect prodrug to be recommended for development is MB7133, a HepDirect oncolytic for treating primary liver cancer. If all goes according to plan we will begin clinical testing of MB7133 next quarter in the United States and Asia. There are currently no approved drugs for the treatment of primary liver cancer. Our preclinical results with MB7133 combined with the early data from the Hepavir B clinical trials increases our confidence in the potential of MB7133 to successfully treat this deadly disease."

Dr. Laikind added " We continue to execute our business model of discovering exciting new drugs to treat important, often deadly diseases and steadily advancing these products through clinical development. When MB7133 enters the clinic next quarter Metabasis will have three products at various stages of clinical development. In addition to Hepavir B and MB7133, our drug for type 2 diabetes, CS-917, a novel gluconeogenesis inhibitor, is being evaluated in phase 2 clinical trials in the United States." Metabasis' partner on that project, Sankyo Co., Ltd, has primary responsibility for developing CS-917.

Metabasis Therapeutics, Inc. (www.mbasis.com) is a privately held, biopharmaceutical company that develops proprietary products for the treatment of human disease with a current focus on liver and liver-related diseases. The Company employs various resources for discovering and perfecting new products, is a leader in the field of nucleoside/nucleotide chemistry and metabolism, and has proprietary expertise in liver biology and liver-specific drug delivery. Metabasis has discovered and developed a new class of drugs for treating diabetes that act to lower liver glucose production in diabetic patients. The first drug from this program, CS-917, is being developed in collaboration with Sankyo Co., Ltd. and is currently undergoing clinical testing. The Company has also developed the HepDirect Prodrug Technology that allows liver-specific delivery of new and existing drugs. Two drugs derived from the HepDirect Technology are in development; a drug for hepatitis B called Hepavir B and a drug for primary liver cancer called MB7133. Hepavir B is the subject of a partnership with Ribapharm, Inc. and is currently being evaluated in patient trials. The drug for primary liver cancer is expected to enter the clinic during the second quarter of 2003. The Company has approximately 80 employees and occupies state-of-the-art research facilities in San Diego, California.