A cardiovascular collaboration

SAARBRUECKEN, Germany—With a mutual goal of developing andcommercializing novel drug candidates targeting cardiovascular disease,ElexoPharm GmbH has entered into a collaboration with Merck & Co.

Under the terms of the agreement, Merck will be responsiblefor development, regulatory filings, manufacturing and commercializationactivities stemming from the collaboration.

Merck will pay ElexoPharm an upfront payment of $1.9 million.In addition, ElexoPharm is eligible to receive up to $41 million if specificdevelopment, regulatory and commercial milestones are achieved for a candidate,as well as royalties on net sales of any products resulting from thecollaboration.

"This agreement marks a major milestone in ElexoPharm'srelatively recent company history," says Prof. Rolf Hartmann, founder andscientific advisor of ElexoPharm GmbH. "We are delighted to have a partner suchas Merck."

Founded in 2005 by Hartmann as a spinoff from the Departmentof Pharmaceutical and Medicinal Chemistry of Saarland University, ElexoPharm isfocused on preclinical medicinal chemistry research concerning the design anddevelopment of new drugs using novel therapeutic approaches for human diseasesthat are currently not or insufficiently treatable with existing drugs.

According to Dr. Ian R. McConnell, Merck's director ofglobal communications, ElexoPharm was an attractive partner for thecollaboration because of the progress it has made in the research ofaldosterone synthase, a steroid hydroxylase cytochrome P450 oxidase enzymeinvolved in the generation of a hormone that increases the reabsorption ofsodium and water and the secretion of potassium in the kidneys. This increasesblood volume, and therefore, increases blood pressure.

"This represents an attractive target for the potentialtreatment of cardiovascular disease," McConnell says. "This agreementunderscores Merck's ongoing commitment to developing breakthroughcardiovascular medicines."

ElexoPharm has licensed its aldosterone inhibitors programexclusively to Merck, and will take part in the further development of theprogram, Hartmann says.

"Certain forms of congestive heart failure, hypertension andother cardiovascular diseases go along with pathophysiologically elevatedaldosterone plasma levels," Hartmann notes. "The goal is to reduce thoseelevated aldosterone plasma levels through an aldosterone synthase inhibitor."

McConnell says ElexoPharm's leading-edge preclinicalmedicinal chemistry research "will enable Merck to explore novel therapeuticapproaches that are currently not or insufficiently treatable with existingdrugs and complements our already strong cardiovascular pipeline."

Moreover, Hartmann points out that the agreement is a giantstep for a budding company like ElexoPharm.

"The agreement itself is a great success for us, but weobviously hope to achieve further milestones," he says.

In addition to its core CRO business, ElexoPharm is alsoundertaking in-house development of drugs that inhibit aldosterone synthase, orthe CYP11B2 enzyme, for the potential treatment of congestive heart failure,myocardial fibrosis and hyperaldosteronism.

CYP11B2 is a key enzyme in mineralocorticoid biosynthesisand catalyzes the conversion of deoxycorticosterone to the most potentmineralocorticoid aldosterone, according to Hartmann. The enzyme is regulatedby several physiological parameters, including therenin-angiotensin-aldosterone-system and plasma potassium concentrations. ElexoPharmhas developed a preclinical portfolio of selective nonsteroidal CYP11B2inhibitors, which it claims have no effect on other steroidogenic CYP enzymesand reduced ACTH-stimulated aldosterone levels in rats.

All of this has Merck officials seeing plenty of promise inthe newly inked collaboration.

"While we cannot speculate as to what will result fromMerck's collaboration with ElexoPharm, we are confident that this venture willdrive innovative research on the treatment of cardiovascular disease," McConnellsays.

As for the collaboration's impact on Merck's pipeline,McConnell notes that it does not serve to replace other drugs.

"Instead, it will expand and complement Merck's ongoingresearch in cardiovascular disease," he says.