Merck & Co, Inc and Portola Pharmaceuticals, Inc have signed an exclusive global collaboration and license agreement for the development and commercialization of betrixaban, an investigational oral Factor Xa inhibitor anticoagulant currently in phase-II clinical development for the prevention of stroke in patients with atrial fibrillation (SPAF).

"Betrixaban represents an important addition to our late-stage portfolio with the potential to be a significant medicine in the Factor Xa inhibitor class," said Luciano Rossetti, senior vice president and franchise head, Atherosclerosis and Cardiovascular, Merck Research Laboratories. "This agreement reinforces Merck's focus on developing an innovative portfolio of products for the treatment and management of multiple aspects of cardiovascular disease."

In return for an exclusive worldwide license to betrixaban, Merck will pay Portola an initial fee of $50 million. Portola is eligible to receive additional cash payments totalling up to $420 million upon achievement of certain development, regulatory and commercialization milestones, as well as double-digit royalties on worldwide sales of betrixaban, if approved. Merck will assume all development and commercialization costs, including the costs of phase-III clinical trials. Portola has retained an option to co-fund phase-III clinical trials in return for additional royalties and to co-promote betrixaban with Merck in the United States.

Betrixaban is an oral anticoagulant agent that directly inhibits Factor Xa, an important validated target in the blood coagulation pathway. Novel oral Factor Xa inhibitors are in development to help address the limitations of current anticoagulants such as warfarin. Warfarin, the most frequently prescribed anticoagulant in North America, is associated with risks of bleeding as well as drug and food interactions that require its use to be routinely monitoredi.

"Merck is a proven global leader and innovator in cardiovascular medicine and is an ideal partner with which to further develop this promising drug," said Charles Homcy, president and chief executive officer of Portola. "This is the second major collaboration we have announced this year validating the high quality of our drug candidates and the expertise of our research and development team. This represents a significant milestone for the company and we now have over $175 million in cash to further advance the rest of our valuable proprietary pipeline."

The effectiveness of the collaboration agreement is subject to the expiration or earlier termination of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act, if applicable, as well as other customary closing conditions.

Betrixaban is an orally available small molecule that has been specifically designed for chronic, once-a-day treatment with a long half-life.

Portola Pharma develops innovative therapeutics based on targets with established proof of concepts that are engineered to provide significant advances over current treatments for cardiovascular disease, inflammatory disease and cancer.