Less than a year after building its pipeline through an acquisition, Renovis Inc. raised $45 million through a Series E round of financing.

"Products are critical," Renovis Chief Financial Officer John Doyle told BioWorld Today, noting the company's three clinical-stage candidates. "The diverse list of product opportunities, backed up by a preclinical program that promises to generate investigational new drug applications in 2004 and 2005, were really the differentiator for investors. And this financing represented an effort to reach out to investors in Asia, Europe and the U.S., and we were fortunate to get interest from all those places."

The South San Francisco-based firm has raised $96 million to date through four rounds of venture financing and an equity issue as part of its acquisition of Centaur Pharmaceuticals Inc. The December purchase of the Sunnyvale, Calif.-based company, in which Renovis exchanged $1.25 million in cash and up to 30 percent of its stock, brought on board two late-stage clinical products, several preclinical compounds and a compound library.

Doyle said the latest financing would last into 2006, during which time Renovis plans to use the funds to push its clinical programs in pain, and also advance preclinical programs in pain and neuroinflammation toward the clinic.

Courtesy of its asset acquisition, privately held Renovis' most advanced drug is advancing in a Phase III program under the stewardship of AstraZeneca plc. From Centaur, London-based AstraZeneca licensed the acute ischemic stroke product, Cerovive (NXY-059). The nitrone, a free radical scavenger, is a neuroprotectant designed for administration immediately following a stroke without the need of a CAT scan. Thrombolytic clot-busting drugs require CAT scans prior to administration, which can cost patients crucial time, Doyle said.

Renovis recently received a $4.5 million milestone payment when AstraZeneca moved Cerovive into a multiyear pivotal program, which will include two 1,500-patient studies. One will focus on U.S. patients, and the other will evaluate the compound in Europe and the rest of the world. Doyle said Renovis would receive similar milestone payments upon AstraZeneca's submission of a new drug application and approval, followed by double-digit royalties if the product is approved.

Its internal clinical pipeline includes REN-1654, a product in a Phase II program for neuropathic pain that also was acquired from Centaur. Doyle said the orally available small molecule was studied for Parkinson's disease dementia, but Renovis decided to initially study the neuro-anti-inflammatory compound in a quicker, less-expensive indication to determine its efficacy.

"And we had excellent results in a number of preclinical models of neuropathic pain that led us in this direction," he added.

Another internal compound, REN-213, is a combination of a kappa opioid called nalbuphine with an antagonist called naloxone. Doyle said that Renovis would file an investigational new drug application in the next two weeks to evaluate the drug in post-operative pain indications, with Phase I trials scheduled to begin later this year.

"Kappa opioids are advantageous because they do not have traditional side effects associated with mu opioids, such as constipation, cognitive impairment and addiction," he added. "So when available, that drug essentially would be a replacement for morphine because it provides similar analgesia without the negative side effects."

Doyle said REN-213's human safety and efficacy already has been studied in investigator-initiated trials.

From its preclinical pipeline, Renovis expects to file an investigational new drug application for a neuropathic pain molecule to follow as a backup for REN-1654. Doyle added that the preclinical neuroinflammation program has reached the lead optimization stage.

New York-based Easton Hunt Capital Partners led the financing and added its managing partner, John Friedman, to Renovis' board in the process. The round also included first-time investments from HealthCap, of Stockholm, Sweden; MDS Capital, of Toronto; Invus Group, of New York; CDIB BioScience Ventures, of Taipei, Taiwan; and others. Returning investors included Alta Partners, of San Francisco; Venrock Associates, of New York; Flagship Ventures, of Cambridge, Mass.; Skyline Ventures, of Palo Alto, Calif.; and HBM BioVentures, of Zurich, Switzerland.