Metabasis Therapeutics and Merck announced this morning that they are joining forces to develop a novel treatment for type 2 diabetes, hyperlipidemia and obesity. At the center of this venture is a tiny molecule that would activate a liver enzyme called AMP-activated Protein Kinase (AMPK). Over the past several years, researchers have seen AMPK as a potential therapy for metabolic diseases.
Using its NuMimetic™ technology, Metabasis research targets molecules that bind to regulatory enzymes in metabolic pathways. By fitting nucleotide binding sites, these potent molecules mimic the natural regulators of enzymes and hence are called nucleotide mimetics. The compound in focus today is an AMP mimetic, which activates a liver protein kinase. The liver protein kinase, in turn, regulates levels of fat and cholesterol. Metabasis has already developed a library of nucleotide mimetics, including ones that appear to lower glucose, cholesterol, and lipids in preclinical models.
As a reminder, Merck is currently working on with Bristol-Myers Squibb on the new drug Pargluva (previously called Muraglitizar), a dual PPAR agonist for the management of diabetes and associated heart disease. Pargluva has not yet been approved by the FDA.
As well, Metabasis currently has two other drug candidates for treatment of diabetes. CS-917, a treatment for type 2 diabetes that was also discovered using NuMimetic technology, is entering Phase IIb clinical trials. Metabasis believes that CS-917 is the first drug candidate to be studied in human clinical trials that is designed to directly block the gluconeogenesis pathway. CS-917 significantly reduced blood glucose levels in patients with type 2 diabetes during two Phase II clinical trials. The other drug candidate, MBO7803, is another type 2 diabetes treatment designed to inhibit gluconeogenesis. MBO7803 is still in pre-clinical development.
This is not the first time that Merck has collaborated with Metabasis—they began working together on a hepatitis C project in 2004. Metabasis and Merck have agreed to each contribute research efforts and drug candidates for the collaboration. Merck will pay $5 million upon signing the agreement and will fund Metabasis for its research input. While Metabasis would receive a royalty on sales if a product is commercialized, Merck will hold primary responsibility, including (importantly) financial responsibility, for the clinical production of any drug therapy resulting from the research. Merck will also hold the right to market any product internationally, while Metabasis may co-promote a product in the United States. It is estimated that Metabasis would receive $54 million, excluding royalties, if a product is marketed for single-indication usage in patients. This cash amount could jump to $74 million if a product is approved for additional indications.
We continue to see huge growth in interest in obesity among pharmaceutical companies. Sanofi-Aventis appears to be the leader, with Rimonabant having been filed with the FDA earlier this year (though it is unclear for what indication - smoking or obesity or otherwise - we ultimately expect at least one indication to be lipids-oriented). Merck currently has three obesity drugs in Phase 2 development, and Lilly announced at a 2004 analyst meeting that it was planning to increase R&D investment in early stage obesity compounds. In late May, Medtronic jumped on the bandwagon by announcing the creation of a new business unit: Medtronic Obesity Solutions.