Resolvyx Pharmaceuticals: Fish-Oil Mystery Solved, Blockbuster Drugs to Follow?
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says Gjorstrup, now Resolvyx’s chief scientific officer. They had two main reservations: Natural resolvins and protectins act locally and typically exist only minutes before getting chewed up by enzymes, hence it seemed unlikely that drugs based on them would last long enough in the body to work. And the lipids’ chemical complexity—chains of 20-plus carbon atoms festooned with side groups—suggested it would cost too much to synthesize them in large quantities.
Eventually, Resolvyx advisor Nicos Petasis, a University of Southern California chemist, helped finesse the synthesis issue. Meanwhile, Serhan’s group and Resolvyx scientists demonstrated that the compounds have surprisingly long half-lives when administered as drugs, and that they show efficacy in animals with various inflammatory illnesses. In December 2005, CHL Medical Partners, Atlas Venture, and Flagship Ventures launched Resolvyx with a $17 million first-round financing. A year ago, Resolvyx’s pace quickened when it hired biopharma veteran (Sepracor, GlaxoSmithKline, Abbott) Paul Rubin as CEO.
Now the company faces an enviable problem: an embarrassment of riches when it comes to possible indications for its medicines. “We have an opportunity to campaign our drugs across a really broad range of conditions,” says Nichols—everything from killers such as heart disease to skin inflammation. But its limited resources necessitate a careful choice. Seeking to ward off heart attacks, for example, would require lengthy clinical trials beyond its means. Instead, the startup plans to try oral doses of a resolvin called RvE1 as a treatment for rheumatoid arthritis, inflammatory bowel diseases, and asthma. It’s also plans early trials with resolvins for diseases such as dry eye, a debilitating condition centrally involving inflammation. Nichols adds that the ability to monitor blood levels of inflammatory “markers” in patients on Resolvyx’s drugs should enable it to quickly establish “proof of concept” in early-stage clinical tests, paving the way to raise the large sums needed for bigger trials.
Resolvyx’s drugs promise to be exceptionally safe—an important plus at a time when one high-flying drug after another has crashed due to unexpected toxicity. Existing anti-inflammatories can precipitate gastric bleeding, immune suppression, and other fallout. In contrast, hefty doses of fish oil have been chronically ingested by millions with minimal adverse effects. (Remember the cod liver oil moms used to foist on grimacing kids?) Omega-3’s natural derivatives could be similarly benign. Serhan explains that the derivatives seem to grease many wheels in cells to normalize an out-of-whack process rather than hitting one or two molecular targets very hard, as do most drugs, inviting side effects.
Still, couldn’t the benefits of Resolvyx’s drugs be attained by simply popping fish-oil pills? Probably not, says Nichols. The hot-selling supplements may be good for lowering disease risks in general population, he adds. But to douse the leaping immune flames underlying diseases such as rheumatoid arthritis—and achieve maximal benefits in clinical tests—will probably necessitate the kind of stronger, precision-manufactured medicine Resolvyx is developing. Besides, many if not most patients would likely balk at chronically gulping fistfuls of omega-3 pills. The resulting fishy burps alone could prove fatal—to their social lives.