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TSI Preps for Trials of New Clot-Busting Drug

Xconomy Boston — 

Ever since Genentech’s clot dissolver known as tissue plasminogen activator, or tPA, hit the market 15 years ago, the pharmaceutical industry has been laboring to come up with something to solve the drug’s main drawback: It has to be given within three hours of a stroke. The folks at Cambridge, MA-based Thrombolytic Science International (TSI) believe they can vastly increase that time window with a drug that will enter clinical trials by the end of this quarter.

TSI was founded in 2006 based on science discovered by the company’s co-founder, Harvard medicine professor Victor Gurewich. He licensed an enzyme called prourokinase (proUK) and participated in research proving that it, too, can dissolve clots—but without the time worries that come with tPA, and with more precise targeting.

One big reason companies are still searching for alternatives to tPA is that it often takes more than three hours for a stroke victim to realize what’s happened to them—let alone to seek treatment. That’s why tPA is only given to about five percent of patients, according to a study in the journal Stroke. “What’s exciting with proUK is the mechanism of action leads to a window of treatment of six hours,” says Alexis Wallace, CEO of TSI.

Wallace says TSI’s drug, called TS01, may offer a safety advantage, as well. That’s because there are two types of clots—“occlusive,” which are the bad kind, and “hemostatic,” which are the normal clots that prevent excessive blood loss—and tPA destroys both. TS01, on the other hand, only busts up the occlusive clots, which may reduce the risk of bleeding that’s commonly seen with tPA. “That’s the main interest in pushing proUK,” Wallace says.

Several pharmaceutical companies tried working with proUK in the 1990s, but struggled to keep the enzyme stable enough so it would only target the occlusive clots. After watching several companies fail, Gurewich went back to the drawing board and kept working on proUK until he came up with a molecule that maintained both its targeting power and its ability to stretch the therapeutic time window.

TSI’s approach combines a mutant form of proUK with a natural plasma inhibitor called C1, which is commonly used to prevent excessive bleeding. The company has demonstrated that C1 promotes the targeting and therapeutic activity of the mutant proUK, “without any detrimental effects on the time it takes to destroy the clot,” Wallace says.

Early human trials with healthy volunteers will start soon and should be completed by the end of this year. The company hopes to be in mid-stage testing with stroke patients in 2013. Rather than taking on Genentech head-to-head, Wallace says, TSI will study its compound in patients who couldn’t be given tPA because of uncertainty about when their strokes occurred.

TSI has raised $8 million in two funding rounds, much of which came from a European trust. That’s enough to get the company through the first round of testing, Wallace says. He says that the company needs to raise another $8 million to $10 million to get through the second round of trials, and it will start looking for a Big Pharma partner after that.

TSI is focusing on stroke for now, but the company’s scientists believe their technology may also be effective in acute myocardial infarction, deep vein thrombosis, and similar disorders where clots are the underlying issue. “Similar to stroke,” Wallace says, “there is a lot of unmet need.”