Editor

Ischemic stroke - it's the category (the other is hemorrhagic) into which about 85 percent of all strokes fall. Blood suddenly stops going to a specific area of the brain because of a blood clot, thus "impairing neurologic function," as the physicians say. In plainer words, the patient might not be able to walk, talk or do much of anything else.

Including stay alive.

Stroke is the leading cause of disability in the U.S. and the third leading cause of death. Available for its unlucky, often-atherosclerotic victims in two types, ischemic stroke might be caused by a clot in an artery that goes to the brain or by one that forms elsewhere and travels to the gray matter. Doctors call the types "thrombotic" and "embolic," respectively.

By any name, ischemic stroke is bad news.

Enter Renovis Inc., which earlier this month reported Phase III data from a trial conducted by licensee AstraZeneca plc that showed the nitrone-based free radical "spin trap" Cerovive helped ischemic stroke patients.

Specifically, preliminary results from the SAINT (Stroke-Acute Ischemic-NXY Treatment) I trial in more than 1,700 patients in Europe and elsewhere showed Cerovive vs. placebo met its endpoint - a statistically significant reduction on the primary outcome of disability three months after an ischemic stroke, as measured by the Modified Rankin Scale.

The "p" value was 0.038. The Wall Street value proved substantial as well. Shares of Renovis skyrocketed 94 percent on the favorable Phase III news.

Except for "some generalized treatment dealing with blood pressure and making people comfortable, there's no treatment other than [tissue plasminogen activator, or tPA]" for ischemic stroke, noted John Friedman, founder and managing partner of Easton Capital Investment Group, a venture capital firm. Easton has been a booster of Renovis, and Friedman serves on the firm's board.

The trouble with tPA is the three-hour window during which the clot buster - in the form of such agents as Genentech Inc.'s Activase (alteplase) - must be given. If a stroke happens during the night, if the hospital is far away, or if the emergency room staff lacks experience, the patient is out of luck. Tests must be done; a clot buster given against hemorrhagic will make the patient bleed out and die.

Cerovive gets around that. It's complementary with tPA and any of the clot busters, and apparently safe for hemorrhagic stroke, Friedman said. A Phase IIb study called CHANT (Cerebral Hemorrhagic and NXY-059 Treatment) is ongoing to test that aspect of the drug. But only a wee percentage of stroke patients get tPA anyway - some 3 percent or 4 percent of the 2.2 million strokes reported every year.

Thirty-six studies have been conducted for stroke therapeutics other than tPA, and "all failed until the Renovis trial," he said, adding that it was the first to satisfy the Stroke Therapy Academic Industry Roundtable guidelines for evaluation.

"Right now we are [with stroke] where we were with trauma 25 years ago," Friedman said. "A lot of trials failed because they were poorly designed. Looking back, you wonder what people were drinking when they designed these trials."

Cerovive, given intravenously, missed a co-primary endpoint - or what the company called a "glorified secondary" endpoint - measuring the change in impairment based on the National Institutes of Health Stroke Scale. But Renovis expects regulators to give more credence to the Rankin results. Investors must be expecting the same.

AstraZeneca, which has exclusive, worldwide rights to Cerovive, is conducting a second Phase III trial, SAINT 2, in North American ischemic stroke patients. Renovis gets milestone payments coinciding with regulatory filings and what the company described as "mid-teen" percentage royalties from a market opportunity potentially worth several billion dollars.

The stroke indication has drawn efforts by other firms, as well. Last summer, Neurobiological Technologies Inc. acquired Viprinex (ancrod) from Empire Pharmaceuticals Inc., a small biotech firm in Greenville, N.Y., with plans for a 12-month to 18-month trial to support a regulatory filing. Derived from Malayan pit viper venom, Viprinex is a thrombin-like enzyme highly specific to fibrinogen.

"But even the ones that are out there are not competitive to Renovis, because they are clot busters," Friedman said.

Easton is a $110 million dollar fund, with only 50 percent of that invested in life sciences - yet the firm was involved in two of the 10 largest funding deals in 2003: Renovis and Acorda Therapeutics Inc. The latter raised $55.3 million in a May round led by Easton, with ABN AMRO Capital, Cross Atlantic Partners, JP Morgan Fleming Asset Management, and Techno Venture Management also participating.

To evaluate a would-be investment as a late-stage or early stage company, Friedman said, is too simplistic, and he pointed to another Easton life-science favorite: Transave Inc., which develops site-specific therapeutics focused on lung diseases, including cancer and infectious diseases.

The company, involving some personnel from The Liposome Co. (now part of Elan Corp. plc), found "a number of drugs out there that would be effective if given locally but given systemically are detrimental." Transave's early product candidates - reformulated versions of already approved drugs - were developed in their updated form through sustained-release lipid inhalation targeting (SLIT) technology. The firm in March started enrolling patients for a Phase II study of SLIT Cisplatin in recurrent osteosarcoma patients with lung metastases.

"Is this an early stage or late-stage company?" Friedman said. "In the simplistic approach, it was pre-'first in man.' On the other hand, it had the time-cost characterizations of a late-stage [firm]."

In selecting an enterprise ripe for VC help, "No. 1 is the quality of the management team," Friedman said.

"Clearly, you want something for which there is a truly unmet need," he said. "Is it a binary product? Are you betting everything on just one? We like companies with a big therapeutic platform, with a whole bunch of shots on goal that are somewhat unrelated."

Renovis also has REN-1654, a TNF-alpha release inhibitor that failed this spring to show efficacy compared to placebo in a proof-of-concept study in post-herpetic neuralgia, but the firm has hopes for the ongoing Phase II study evaluating the product in sciatica. Results are expected in the third quarter.

Further back in the pipeline is REN-850, in a Phase I program in multiple sclerosis and other autoimmune diseases. Its mechanism of action to inhibit leukocyte trafficking is similar to the MS drug Tysabri, pulled off the market by Biogen Idec Inc. and Elan, due to deaths linked to progressive multifocal leukoencephalopathy. That means Renovis will be taking a hard look at safety before going ahead.

In the spotlight, meanwhile, is the stroke drug.

"This is a humongous market, which is unserved," Friedman said, singing the praises of Cerovive. "There's nothing else close."