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Extramural Grantee Gets Funding for Clinical Trials

By Eddy Ball
July 2007

Bruce Hammock
For Hammock, caterpillars, such as the one on his finger, turned out to be the source of inspiration for the process that may be "the first new target for hypertension in twenty years." (Photo courtesy of Bruce Hammock and the University of California at Davis)

Long-time Extramural Grantee Bruce Hammock, Ph.D., recently received the kind of good news researchers long to hear. Arête Therapeutics, Inc., a privately held biopharmaceutical company, announced in May that it had raised $35 million in venture capital to initiate clinical trials for a family of compounds developed by Hammock. During discovery-phase studies, the compounds showed considerable promise for effective treatment of hypertension and inflammation.

This latest influx of investment brings the total Series A funding for developing Hammock's discovery to $51 million. Arête anticipates beginning a phase 1a/1b clinical trial for its soluble epoxide hydrolase (sHE)- inhibitor-based Investigational New Drug (IND) candidate, currently dubbed AR9281, by the end of the year.

Hammock is a distinguished professor at the University of California at Davis and a prolific researcher who has received NIEHS grants since 1973. He is director of the NIEHS-UC-Davis Superfund Basic Research Program.

Hammock's research into the basic biology of how caterpillars turn into butterflies led to discoveries about the novel enzyme and its relationship to several disease conditions in mammals. Hammock found that inhibiting the action of sEH blocked the breakdown of fatty acids in the epoxygenese branch of the arachidonic acid cascade. These fatty acids, called epoxy-lipids, have vasodilation and anti-inflammatory effects that can help restore the balance of fatty acids - and counter the influence of the products of the arachidonic cascade that promote inflammation, pain and hypertension.

"The practical success of this work is a testament to the value of fundamental science," Hammock observed in the press release from Arête. "This work started asking about the basic biology of how insect caterpillars turn into butterflies, and now may lead to a valuable new class of molecules for treating serious human disease."

Hammock has repeatedly acknowledged the importance of NIEHS support in his research into sEH and sEH inhibition. During his Distinguished Lecture(http://www.niehs.nih.gov/factor/issues/2006nov.pdf)Iwasaspan at NIEHS in October 2006, he said, "The work has been funded probably 10 percent by the Department of Agriculture and 90 percent by the NIEHS [Superfund Basic Research Program]."

Among Hammock's more than 650 peer-reviewed publications are a series of collaborations with NIEHS colleagues, including Senior Scientist Darryl Zeldin. One of their studies(http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=16595607&query_hl=10&itool=pubmed_docsum)Iwasaspan Exit NIEHS identifying a genetic polymorphism, K55R, associated with elevated levels of sEH, was recognized as a major 2006 intramural research accomplishment by NIH.

Arête plans to focus on diversifying the proprietary family of the inhibitors by increasing specificity, stability and solubility (oral availability) of the compounds before selecting an IND to undergo toxicity testing. If clinical trials proceed as expected, the new drug will take five to six years to undergo the rigorous testing phases required for FDA approval.



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