Metabasis Therapeutics, Inc. Comments On Positive Data Reported At AASLD Late-Breaker Session By Valeant Pharmaceuticals International From Pradefovir Mesylate Phase 2 Study

SAN DIEGO, Nov. 15 /PRNewswire-FirstCall/ -- Metabasis Therapeutics, Inc. today commented on the 24-week interim data reported on Monday, November 14, 2005 by Valeant Pharmaceuticals International at a late-breaking news session of the 56th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD). As has been previously reported, the interim data from this Phase 2 trial of the oral anti-viral compound pradefovir showed that the pradefovir 30mg QD cohort achieved a 5.02 log(10) drop in viral titers from baseline compared to a 3.66 log(10) drop in the 10 mg QD Hepsera(R) (adefovir dipivoxil) group (p <0.001). Pradefovir also reduced viral titers significantly better than 10 mg QD Hepsera at 10 and 20 mg doses. Data was also presented that showed that the percentage of patients achieving undetectable HBV DNA (<400 c/mL) was significantly greater for patients receiving pradefovir compared to those receiving 10 mgQD of Hepsera at doses of 10mg, 20mg and 30mg QD.

The safety and efficacy of pradefovir is being studied for the treatment of compensated chronic hepatitis B (HBV). Pradefovir is a prodrug of adefovir that was discovered by Metabasis and uses Metabasis’ HepDirect(TM) technology which is designed to deliver higher concentrations of adefovir to the liver, the primary site of HBV replication, while minimizing the levels of circulating adefovir and thus reducing exposure to the kidney where adefovir is believed to cause toxicity at high concentrations. Hepsera was approved for use at 10 mg QD, however, previous clinical trials showed that at a dose of 30 mg QD and above Hepsera was associated with evidence of potential kidney toxicity. Data presented yesterday showed that adefovir exposure with 30 mg QD pradefovir was less than with 10 mg QD Hepsera (AUC 224 vs 298 ng.h/mL).

Metabasis licensed pradefovir to Valeant under an agreement that included payment of a license fee and provides for additional payments upon the occurrence of certain milestones and payment of royalties to Metabasis on net sales should the product be approved for marketing and successfully commercialized.

The Phase 2 study conducted by Valeant is an open-label, randomized, multiple dose study with 242 patients enrolled at 21 sites in the United States, Taiwan, Singapore and South Korea. Approximately half of the patients had been previously treated ineffectively with other drugs, and 70 percent of the patients were HBeAg positive. Patients that have been previously treated ineffectively are considered to be more difficult to treat. The Phase 2 study consists of five treatment groups: pradefovir -- 5, 10, 20 and 30 mg/day, and Hepsera -- 10 mg/day, with an overall treatment duration of 48 weeks. The interim 24-week data reported by Valeant indicates that pradefovir resulted in differences in the percentage of patients achieving undetectable HBV DNA summarized as follows:

Pradefovir Phase 2 - Interim Week 24 Results (all patients) Percent of Patients < 400 c/mL Dose HBeAg (+) HBeAg (-) Median Baseline VL %<400c/mL Median (Log(10) by Baseline VL %<400c/mL N c/ml) week 24 N Log(10)c/mL) by week 24 Hepsera 10 mg QD 36 8.3 8% 14 6.7 36% Pradefovir 5 mg QD 33 8.4 3% 14 6.8 50% 10 mg QD 33 8.7 15% 16 7.0 44% 20 mg QD 31 8.7 23% 17 6.9 41% 30 mg QD 36 8.6 31% 12 7.8 58% In July 2005, Valeant reported interim 24-week data indicating that pradefovir demonstrated a significant decline in HBV DNA summarized as follows: Pradefovir Phase 2 - Interim Week 24 Results Mean Log(10) HBV DNA Decline From Baseline (Intent-to-Treat Analysis) Baseline Week 24 Mean Mean P-Value Number HBV DNA Decline Compared to of (Log(10) in Hepsera Dose Patients copies/mL) HBV DNA Control Hepsera 10 mg QD 50 8.0 -3.66 N/A Pradefovir 5 mg QD 47 7.9 -3.39 0.262 10 mg QD 49 7.9 -4.22 0.012 20 mg QD 48 8.0 -4.33 0.004 30 mg QD 48 8.2 -5.02 <0.001

The interim results have shown no evidence of nephrotoxicity. There were no serious adverse events related to treatment. The most frequently reported adverse events were similar across all treatment groups, including Hepsera. No dose-related trends regarding safety were identified, and no events resulted in a patient being withdrawn prematurely from treatment.

Paul Laikind, Ph.D., Metabasis’ chairman, president and chief executive officer said, “The additional results presented by Valeant yesterday further support the potential of pradefovir. The robust and significant reduction in viral load after only 24 weeks of treatment coupled with the apparent safety and lack of nephrotoxicity and low circulating adefovir levels suggests that this product could turn out to have a significant competitive advantage in the marketplace. If the results reported today are confirmed in future studies, pradefovir could provide physicians and patients with a new therapeutic approach that may significantly improve the treatment of this difficult disease.”

Patient participation in the Phase 2 trial is expected to be completed early in 2006. Valeant has reviewed interim 24-week results from the Phase 2 trial with the Food and Drug Administration (FDA) and intends to initiate Phase 3 trials by mid-2006.

About Hepatitis B

Hepatitis B is a potentially fatal disease that can lead to complications such as cirrhosis and liver cancer. Approximately two billion people worldwide are estimated to have hepatitis B, with 350-400 million people estimated to be chronically infected. According to a recent study, the HBV market currently represents more than $1 billion in annual sales, and is expected to grow to over $2.8 billion by 2012.

Pradefovir is an investigational compound which has not been found by the FDA or any other regulatory agency to be safe or effective in the diagnosis, mitigation, treatment or cure of any disease or illness. It may not be sold or promoted in the United States unless and until a New Drug Application has been filed with and approved by the FDA. Similar restrictions apply in other countries.

About Metabasis (www.mbasis.com):

Metabasis Therapeutics is a biopharmaceutical company uniquely focused on the discovery, development and eventual commercialization of novel drugs to address some of the world’s most widespread and costly chronic diseases involving pathways in the liver. 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 major 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(TM) 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 efficacy, safety and potential further development and clinical trials of pradefovir, as well as the potential and progress of the Company’s other clinical and preclinical compounds. 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 Metabasis’ dependence on Valeant and its other licensees and collaborators for the clinical development and registration of its product candidates, among other things; the progress and timing of clinical trials for pradefovir and Metabasis’ other product candidates; the ability to duplicate results from early stage clinical trials in later stage clinical trials; 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 September 30, 2005. 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.

CONTACT: Paul Laikind, Ph.D., Chairman, CEO & President of MetabasisTherapeutics, Inc., +1-858-622-5550

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