Metabasis Therapeutics Presents Preclinical Data on CS-917 and MB07811 at the American Diabetes Association Meeting
- Category: Small Molecules
- Published on Tuesday, 26 June 2007 04:00
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SAN DIEGO, CA, USA | June 25, 2007 | Metabasis Therapeutics, Inc. (Nasdaq:MBRX), a biopharmaceutical company focused on the discovery, development and commercialization of novel drugs for the treatment of metabolic and liver diseases by targeting the liver and liver pathways, announced today that the Company presented two posters at the 67th scientific sessions of the American Diabetes Association (ADA) in Chicago. The posters, entitled, "MB06322 (CS-917), But Not Metformin, Lowers Blood Glucose by Inhibiting Gluconeogenesis in Zucker Diabetic Fatty Rats," and "MB07811, a Liver-Targeted Prodrug of a Novel Thyroid Hormone Receptor Agonist, Lowers Plasma Cholesterol in Cynomolgus Monkeys as Effectively as Atorvastatin," were presented on Sunday, June 24th. Two other posters on CS-917 and one abstract will be presented at ADA by Metabasis' partner, Daiichi Sankyo.
The first Metabasis poster provides data that show that CS-917, the Company's first generation product candidate that is currently being evaluated in clinical trials as a novel treatment for patients with type 2 diabetes, significantly lowered blood glucose in Zucker diabetic fatty (ZDF) rats by inhibiting gluconeogenesis and endogenous glucose production. While metformin, a commonly used treatment for type 2 diabetes, also lowered blood glucose, it did not inhibit gluconeogenesis or endogenous glucose production in this animal model. In isolated liver cells, CS-917 inhibited glucose production greater than 1000-fold more potently than metformin and, unlike metformin, did not prevent the metabolism of lactate or cause excessive lactate production.
The presentations by Daiichi Sankyo are entitled: "CS-917, a Fructose 1,6-Bisphosphatase Inhibitor, Suppresses Gluconeogenesis in Human Hepatocytes, whereas Metformin Stimulates Glycolysis in Caco-2 Cells;" "Enhancement of Insulin Signaling Suppresses Lactate Elevation induced by CS-917, a Fructose 1,6-Bisphosphatase (F1,6-BPase) Inhibitor;" and "Pharmacokinetics and Pharmacodynamics of Single-Dose CS-917, a Novel Prodrug of a Fructose 1,6-Bisphosphatase Inhibitor, in Patients with Type 2 Diabetes."
CS-917 is a prodrug of an orally active, potent, and selective inhibitor of fructose-1, 6-bisphosphatase (FBPase), a regulatory enzyme in the pathway responsible for the production of glucose in the liver, known as the gluconeogenesis pathway. By specifically inhibiting this pathway, liver glucose production should be reduced and blood sugar levels decreased in patients with diabetes, independent of insulin levels and disease stage. A Phase 2b study for CS-917 was recently completed by Daiichi Sankyo.
In addition to CS-917, Metabasis has a second generation product candidate being studied in clinical trials as a treatment for patients with type 2 diabetes, MB07803, that also inhibits gluconeogenesis by inhibiting FBPase. MB07803 is currently in a Phase 2a clinical trial, with results expected toward the end of the year.
"Most drugs on the market today enhance glucose removal and/or act as modest, indirect inhibitors of endogenous glucose production," stated Mark Erion, executive vice president, research and development and chief scientific officer. "In contrast, we believe that CS-917 is the first product candidate to be studied in human clinical trials that directly inhibits the pathway responsible for the excessive glucose production that occurs in patients with type 2 diabetes. Two proof-of-concept studies involving oral administration of CS-917 to patients with type 2 diabetes for 14 days and 28 days demonstrated CS-917 to be well tolerated and to result in statistically significant glucose reductions compared to placebo."
Metabasis' second poster shows that MB07811, the Company's novel product candidate for the treatment of hyperlipidemia, dose-dependently decreased total and LDL-cholesterol in monkeys with a maximal efficacy similar to atorvastatin (Lipitor(R)). MB07811 is a liver-targeted, beta-subtype-selective thyroid hormone receptor (TR beta) agonist that represents the first of a novel class of product candidates discovered by Metabasis. This product candidate is designed to lower serum cholesterol and triglycerides with an improved therapeutic index over thyroid hormone itself or non-liver-targeted TR beta agonists. The first human clinical trial for MB07811 was completed late in 2006 and a Phase 1b clinical trial was initiated last week.
"CS-917 and MB07811 represent novel approaches to treating two of the most pervasive and destructive chronic diseases known, type 2 diabetes and hyperlipidemia," commented Paul Laikind, president and chief executive officer. "Both diseases often lead to debilitating and life threatening complications and both remain poorly controlled in many patients. If approved for use, our products could find broad utility as effective new approaches for treating patients with these metabolic disorders."
Metabasis Therapeutics is a biopharmaceutical company focused on the discovery, development and commercialization of novel drugs to address some of the world's most widespread and costly chronic diseases. By applying our proprietary technologies and scientific expertise, including unique capabilities for targeting the liver and liver pathways, the Company has established a pipeline that includes preclinical and clinical product candidates targeting 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(R) technologies. Metabasis is continuing to identify and develop new product candidates using its proprietary technologies and expertise.
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 initiation, progress, completion and results of pre-clinical and clinical trials for CS-917 and MB07811, including the expected timelines for the initiation of additional clinical trials of those product candidates; and the potential safety and efficacy and further development of CS-917 and MB07811. 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 development for Metabasis' product candidates; the fact that positive results obtained during early development do not necessarily mean later development 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 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, 2007 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.
SOURCE: Metabasis Therapeutics, Inc.