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Hepatitis New Drug Research
  This company says they have unique technologies to develop drugs for hepatitis and metabolic diseases such as diabetes & hyperlipidemia. The hepatitis C & B development program and their development techniques are described below. A 28-day study in patients of their hep B drug remofovir was reported at AASLD in November 2004. It appeared safe and at the highest dose studied 30 mg/day HBV DNA was reduced by 2.66 log. Here is link to report from AASLD on remofovir:
"Metabasis Therapeutics Announces an Extension and Expansion of Its Existing Collaboration With Merck & Co., Inc. To Develop New Treatments for Hepatitis C"
THIS INFORMATION IS FROM THE COMPANY: Liver diseases such as hepatitis B, hepatitis C, primary liver cancer and liver cirrhosis represent some of the most widespread and serious diseases in the world. Metabolic diseases such as type 2 diabetes, hyperlipidemia, obesity and non-alcoholic steatohepatitis are major healthcare problems worldwide as well, but are especially prevalent in the U.S. and Europe. We believe that these diseases can be treated by targeting pathways that reside in the liver. Our proprietary HepDirect liver targeted prodrug technology gives us a competitive advantage for targeting many of these important diseases. As a group, liver and metabolic diseases present one of the largest pharmaceutical markets. According to IMS Health, an independent market research organization, worldwide sales of drugs targeting these diseases exceeded $30 billion in 2002.
MB07133, a HepDirect Oncolytic for the Treatment of Primary Liver Cancer
MB07133 is an intravenously administered product candidate currently being studied in a clinical trial designed to evaluate safety and preliminary efficacy in a limited number of patients with primary liver cancer. Few treatment options exist for these patients - no drug has been approved for the treatment of primary liver cancer. MB07133 is a HepDirect prodrug of araC, an anti-cancer drug that is used to treat leukemia but is ineffective against primary liver cancer. AraC's anti-cancer activity is associated with its ability to be converted to its biologically active form, araCTP. However, AraC is not converted to araCTP in the liver due to the lack of an enzyme in the liver that is required for the first step in the activation pathway of the drug. MB07133 uses our HepDirect technology to target an activated form of araC specifically to the liver thus bypassing the missing enzyme. Once in the liver cell the activated form is rapidly converted to araCTP, the cancer killing form. We believe that MB07133 may provide a means to effectively treat primary liver cancer while minimizing systemic exposure and the resulting side effects that are associated with araC. We have retained full worldwide commercialization rights to MB07133.
Remofovir, a HepDirect Prodrug of a Proven Antiviral for the Treatment of Hepatitis B
Remofovir mesylate is an oral product candidate that is in Phase II clinical development for hepatitis B, a poorly treated and serious liver infection. Remofovir is a HepDirect, liver targeted prodrug of the proven antiviral drug adefovir. The most recently approved hepatitis B drug is Hepsera. Hepsera is also a prodrug of adefovir but it is not liver specific. Hepsera offers advantages over existing drugs because it does not induce viral resistance, but toxicity issues related to renal exposure to adefovir limit the doses at which it can be administered and therefore limits its efficacy for treating this disease. Remofovir, on the other hand, uses our proprietary HepDirect technology and is designed to deliver high concentrations of adefovir to the liver, while limiting the amount of adefovir generated outside of the liver. We believe that this will significantly reduce dose-related toxicities. In pre-clinical and clinical studies, remofovir has been shown to be well-tolerated and to result in elevated levels of the active form of adefovir in the liver without significantly increased levels in other tissues. Clinical proof of principle was recently demonstrated in a study designed to evaluate the safety and preliminary efficacy of the drug in patients with hepatitis B. The patient groups treated with the drug had a statisically significant reduction in hepatitis B virus levels as compared to patients that received a placebo. We are developing remofovir in partnership with Valeant, to whom we have licensed worldwide commercialization rights. Remofovir was formerly called Hepavir B.
Collaborating with Merck to Discover HepDirect Antiviral Drugs for the Treatment of Hepatitis C
Hepatitis C is a viral disease that causes inflammation of the liver that may lead to cirrhosis, primary liver cancer and other long-term complications. According to the World Health Organization, up to 3% of the world population has been infected with hepatitis C. The Centers for Disease Control and Prevention reports that nearly 4 million people in the U.S. are infected with hepatitis C with 2.7 million chronically infected. In December 2003, we entered into a collaborative agreement with Merck to create HepDirect prodrugs of certain compounds that Merck is supplying to us. These compounds target the hepatitis C virus residing in the liver. We will make and conduct initial testing of resulting HepDirect antiviral compounds. All of our activities under the collaboration are being funded by Merck. In addition, Merck is solely responsible for conducting and funding all development work for compounds resulting from this collaboration and for commercializing any resulting products. If a product is successfully developed, Metabasis will receive substantial milestone payments and will receive a portion of the revenue from sales of the drug.
HepDirect Technology
We use our HepDirect prodrug technology to target drugs to the liver, resulting in increased levels of the pharmacologically active form of the drug in the liver and decreased levels in non-liver tissues. This is accomplished by chemically modifying a drug to render it inactive until the modification added is cleaved off by a liver specific enzyme. The modified, inactive form is known as a HepDirect prodrug. We believe this will significantly improve efficacy and safety of certain drugs. Our HepDirect technology can be used to improve certain currently marketed drugs or applied to certain drug candidates, resulting in new, proprietary drugs that may then be marketed by us or by companies we collaborate with that have compounds that would benefit from this approach. Remofovir and MB07133 use our HepDirect technology, as do several of our advanced research programs. In addition to our internal programs, we have a collaboration with Merck to discover new treatments for hepatitis C by applying our HepDirect technology to certain compounds supplied by Merck. We plan to similarly leverage this technology with other companies that have drugs that would benefit from the HepDirect approach.
We have extensive expertise in liver diseases and in the pathways and proteins residing in the liver that significantly contribute to certain metabolic diseases. In addition, we have developed know-how for exploiting certain pathways that are important for transporting drugs into the liver, acting upon them and expelling them from the body, processes referred to as drug uptake, metabolism and excretion, respectively. With this knowledge and expertise, we developed two proprietary technologies, named NuMimetic and HepDirect, which we have used to develop our current product candidates and which we expect to use to expand our product pipeline in the future.
NuMimetic Technology
We use our NuMimetic technology to discover molecules that bind effectively and specifically to certain regulatory sites, called nucleotide binding sites, residing on proteins called enzymes that often control metabolic pathways in the liver and elsewhere. We have developed a library of these unique molecules, known as nucleotide mimetics, and have used this library to discover compounds that we believe have the potential to treat certain metabolic diseases including diabetes and hyperlipidemia. We used our NuMimetic technology to discover CS-917 and MB07803, and we are also using it in certain of our advanced research programs.
Company press release
SAN DIEGO, Jan. 25 /PRNewswire-FirstCall/ -- Metabasis Therapeutics, Inc. announced today that it has extended and expanded a hepatitis C collaboration that was established with Merck in December 2003. The companies will continue their joint efforts to identify novel small molecule therapeutics for the treatment of hepatitis C virus infections (HCV) for an additional twelve months, through December 2005.
Under the extension, which was permitted under the terms of the existing agreement, Merck will continue to contribute drug candidates to the collaboration and fund Metabasis' efforts to apply its technologies to those candidates with the goal of producing a candidate suitable for clinical development. The agreement was expanded to provide for use of certain other technologies in addition to Metabasis' proprietary HepDirect(TM) technology.
Metabasis has developed expertise and technology for improving drugs that act primarily in the liver. One example is the Company's proprietary HepDirect technology, a prodrug technology that specifically targets production of the biologically active form of certain drugs to the liver. Preclinical studies have shown that use of the HepDirect technology may result in higher active drug concentrations in the liver and decreased exposure to non-liver tissue. Accordingly, HepDirect prodrugs may have the potential to improve efficacy, reduce toxicity and thus improve the treatment of liver and liver-related diseases. Metabasis' HepDirect product candidate for the treatment of Hepatitis B is currently in Phase II clinical development.
"We view Merck's decision to extend the collaboration as a further validation of our technologies, our team and the exciting progress made to date in this program," said Dr. Mark Erion, Metabasis' Executive Vice President of Research and Development. "We look forward to building on that progress during the second year of the collaboration and are optimistic that together we may successfully discover potential new treatments for HCV."
It is estimated that up to 3% of the world population has been infected with HCV, according to NHANES III (Third National Health and Nutrition Examination Survey), which means there are more than 170 million chronic carriers at risk of developing liver cirrhosis and/or liver cancer. Nearly 4 million Americans are infected with HCV and about 2.7 million Americans (70%) of those are chronically infected with HCV. In 2002 the NIH issued a report that conservatively estimated that HCV is responsible for 10,000 to 12,000 annual deaths in the United States, where the number of people diagnosed with chronic HCV is expected to increase fourfold from 1990 to 2015.
About Metabasis (http://www.mbasis.com)/
Metabasis Therapeutics, Inc. 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 has three internally discovered, novel product candidates in clinical development: CS-917, pradefovir mesylate (previously known as remofovir) and MB07133, indicated for the treatment of type 2 diabetes, hepatitis B and primary liver cancer, respectively. All three products are being studied in patients and preliminary evidence of efficacy has been demonstrated with CS-917 and pradefovir mesylate. Metabasis has developed several proprietary technologies for use in discovering and optimizing drugs, including the NuMimetic(TM) technology and the HepDirect(TM) technology. The NuMimetic technology was used to discover CS-917, a first-in-class gluconeogenesis inhibitor, and was also used to identify MB07803, a 2nd generation gluconeogenesis inhibitor that is expected to enter the clinic in 2005 for the treatment of type 2 diabetes. The HepDirect technology, a liver-targeting prodrug technology, was used to develop pradefovir mesylate and MB07133 and is also being used in a partnership with Merck to discover new treatments for hepatitis C. Metabasis is continuing to identify and develop new product candidates using its proprietary technologies and know-how.
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 progress, goals and success of Metabasis' collaboration with Merck to develop new treatments for hepatitis C, Metabasis' progress on its other strategic goals and pursuit of its corporate objectives, the completion of clinical trials for Metabasis' product candidates, the expansion of Metabasis' product pipeline, and the designation of additional product candidates from Metabasis' advanced research programs, and the strength of Metabasis' proprietary position as well as other statements about Metabasis' proprietary technologies, product candidates, research programs and collaborations. 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 pre-clinical 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; adverse side effects or inadequate efficacy of Metabasis' product candidates or proprietary technologies; Metabasis' dependence on Merck and its other licensees and collaborators for the clinical development and registration of its product candidates including any product candidates yielded in Metabasis' collaboration with Merck, among other things; 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 quarter ended September 30, 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.
Metabasis Therapeutics, Inc.
CONTACT: Paul Laikind, Ph.D. of Metabasis Therapeutics, Inc.,+1-858-622-5550, or Susan Neath of Atkins + Associates, +1-858-527-3486, forMetabasis Therapeutics, Inc.
Web site: http://www.mbasis.com/
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