An affiliate of Merck & Co. has exercised its option to exclusively license from Xenon Pharmaceuticals small molecule compounds for a new, undisclosed target for potential treatment of cardiovascular disease—a category where the pharma giant suffered Phase III failure in December.

“The discovery of loss-of-function mutations for this target in humans with protective cardiovascular profiles was central for the development of compound modulators of the target,” Simon Pimstone, Xenon’s president and CEO, said in a statement.

Merck’s exercise of its option comes four years after the two companies launched a strategic alliance focused on cardiovascular disease. Since 2009, Xenon said, it has received from Merck milestone payments and an option fee and is eligible for up to $86.5 million in additional payments from the pharma giant tied to further research, development and regulatory milestones. Merck has also agreed to pay Xenon undisclosed royalties on sales of products resulting from the collaboration.

Xenon agreed to use its human clinical genetics platform to validate new cardiovascular targets, selected by a joint steering committee, then collaborate with Merck on discovery and development of small molecule compounds for those targets.

Xenon’s platform uses extreme and opposite phenotypes relevant to cardiovascular disease. The collaboration with Merck was aimed at developing drugs targeting the targets toward treatment of atherosclerosis, Xenon states on its website.

At the time their collaboration was announced, Merck promised in return to pay Xenon research funding and option exercise fees, research, development, and regulatory milestone payments of up to $94.5 million for the first target and up to $89.5 million for each subsequent target. The total value of the collaboration was not disclosed.

The partnership with Merck marked Xenon’s fifth with a pharma giant. In a statement at the time, Xenon’s CSO Michael Hayden cited what he called Merck’s “significant presence in and commitment to the cardiovascular space.”

Last year at the European Society for Cardiology 2012 Congress, in Munich, Germany, Merck said it planned to apply for marketing approvals for two new cardio drugs this year—vorapaxar for acute coronary syndrome chest pain caused by coronary artery disease, and K-524A (tredaptive), for LDL (bad cholesterol) to reduce incidence of vascular events.

But in December, tredaptive failed a Phase III trial after enrolling more than 25,000 patients with a high risk for CV events. Merck acknowledged tredaptive produced no significant risk reduction for coronary deaths, nonfatal heart attacks, strokes or revascularizations compared to statin therapy, while increasing “incidence of some types of nonfatal serious adverse events in the group that received extended-release niacin/laropiprant.”

Xenon says it focuses on rare inherited human diseases representing severe and extreme forms or the opposite presentation of common diseases. In addition to CV disorders, other medical areas of focus for the company include pain, anemia, and metabolic disease. 

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