The following is the second in a series of features on Wisconsin companies that are doing promising work in the global fight against cancer.
Ask anyone in the business world and they’ll tell you there’s no stopping biotech. Particularly in Madison, where biotechnology pioneers like James Thomson have attained something approaching demiurge status, the sector is almost universally seen as the wave of the future.
Of course, that doesn’t mean it can’t be slowed down.
Centrose CEO James Prudent has seen enough of the ebbs and flows of the biotech industry to keep his feet firmly planted on the ground, even if his ambitions might lead some to believe his head is in the clouds.
A graduate of UW-Madison who received his Ph.D. in chemistry at UC-Berkeley, Prudent has been in the biotech game for around 25 years. In that time, he’s worked for industry leaders such as IGEN International (which was acquired by Roche in 2003), Third Wave Technologies (now Hologic), and EraGen. At Third Wave, he helped develop a technology that he later helped turn into a multimillion-dollar product line.
He was on the scene in the ’90s when Bill Clinton and U.K. Prime Minister Tony Blair came out against companies’ patenting genes in humans – a move that he says “totally tanked the market.” Then, he recalls, the early 2000s dot-com bust dealt biotech another blow. These were harsh lessons that led Prudent to conclude that caution is sometimes the best course, even in a sector that potentially offers outsized gains for entrepreneurs.
So perhaps he was positioned better than most when the late-2000s subprime mortgage crisis sent the economy reeling and ushered in more trying times for biotech.
“It’s been a disaster. A disaster. An absolute disaster,” said Prudent of the global financial crisis and its aftermath. “I can send you article after article talking about the numbers, but for biotech, it’s been a complete disaster. To me, I can look at that in two ways. I tend to look at it, well, there are so many biotechs now that have spent so much money and became too top-heavy and couldn’t weather the storm. I’ve been very prudent about bringing our technology to the marketplace and have not spent a lot of money.
“I try to maintain – what I call it is running on yellow. So for people who are into car racing, this is the idea where, if there’s a crash out on the track, you probably want to be working to make sure the car is in good shape because the track is going to open at some point. So I’m hoping that the track opens sooner than later, obviously.”
Windows of opportunity
Of course, the economy hasn’t slowed Prudent’s company to a stop, or even a crawl. It currently has four drugs in its product pipeline, all of which are based on the company’s unique EDC (extracellular drug conjugate) technology.
While the finer details of the technology are best left to the folks in lab coats, the gist is this:
EDC technology uses an antibody, an anti-cancer drug, and a linker that connects the two. The antibody is able to target specific diseased cells, and the drug, which is attached to the antibody, kills those cells.
The technology is similar to ADC (antibody-drug conjugate) systems that have been developed by companies like Roche and Seattle Genetics, which own the first two FDA-approved ADCs. By targeting cancer cells more directly than traditional chemotherapies do, those systems cause fewer side effects and have a larger therapeutic window, which is crucially important in the pharmaceutical industry.
“So you can drink so much water and it will kill you, so there’s a huge therapeutic window there, right, because you can drink a little water and feel pretty good, but you can drink an awful lot of water and it won’t hurt you,” said Prudent. “Drugs are usually a little different, especially the drug class we’re using, which you can give someone one nanomolar, which is a very small amount in the blood, but if you go to 10, you’ll actually start to see some serious heart problems. …
“So the drug has a very small therapeutic window, meaning it’s potent, very potent, but it’s also very toxic. The best drugs are the ones that are real potent but have no toxicity, and what that basically says is you’re moving them directly to where you want them to go, and they’re very specific for the disease that you’re targeting.”
What Centrose hopes to do with its EDC technology is widen the therapeutic window of anti-cancer drugs even further than ADC systems have done. Because the drug stays linked to the antibody and is not internalized into the cancer cell (as it is with ADC systems), it is able to act on additional targets and off-target side effects are eliminated.
(Those who appreciated the easy-to-follow video explanation of the fictional genetic engineering process used in the movie Jurassic Park might want to click here for a better, more thorough rundown of EDC technology.)
While improving the efficiency of anti-cancer drugs is exciting from a merely scientific standpoint – Prudent says his company has demonstrated it can increase the potency of a drug by about a hundredfold and can decrease its toxicity by 500- to 1,000-fold – the implications for cancer patients would be nothing short of miraculous.
“If you know anyone who’s ever had a standard regimen of radiation or chemotherapy, they’re losing their hair, they’re not doing very well, they look sickly, they lose bodyweight, they typically have vomiting, there’s all types of toxic effects that occur with those drugs that have nothing to do with killing the cancer,” said Prudent. “The point of those drugs is, well, we have to give so much that the cancer then dies quicker than the rest of the body, so the future is to target these very potent drugs only to the cancer and away from all the normal tissue, and that’s what we’re trying to do.”
Leading the way
Centrose’s lead drug is EDC1, which is designed to target metastatic cancer – a late-stage cancer that spreads throughout the body and is often hard to treat through conventional therapies. That drug has been found to be safe at effective doses in non-human-primate studies and is now ready to be tested in humans.
That will take money, but the payoff could ultimately be big, particularly in light of EDC technology’s potentially wide applicability, which could extend to everything from diabetes to inflammation to infectious diseases.
“The beauty of Centrose is we have a technology that can crank out a lot of different drugs,” said Prudent. “Right now, we’re just looking into oncology because we don’t have the bandwidth to expand into other indications, but this kind of chemistry that we’re developing can clearly go into multiple areas. Another benefit of the EDC platform versus the ADC platform is that we can actually target drugs to a lot of different diseases.”
But even with the potential the company has been able to show thus far, it still faces an uphill climb – perhaps the steepest part of that being financial. Centrose has hired a New York banker to help raise the money required to get the drug into the clinic, but as Prudent notes, the financial environment is not as favorable to biotechs as it was before the Great Recession sent investors scurrying.
“I think the take-home message today is that there’s a lot of risk-averse companies out there, not only Big Pharma but also the venture capital world,” said Prudent. “The pharma part of it I don’t really understand because their pipelines are drying up and they have a lot of money sitting in the bank. Typically, that can be good and bad. I think what we found is what they’re doing is acquiring bigger companies with those bigger lumps of money, and the venture capital groups just don’t have very much money anymore.”
Home field advantage
As with many leaders in the biotech industry, Prudent is happy to be in Madison, citing its highly educated pool of workers and its strong ties to the university. But he thinks the area and the state could do a better job in keeping biotech companies here once they’ve moved beyond the fledgling stage.
“I would hope that we could play it smart and maintain our position in Wisconsin as long as possible at Centrose and not get acquired, because that really is the way to create jobs,” said Prudent. “If you get acquired – you just saw this with Third Wave, they’re closing doors now, and that’s because Third Wave isn’t really Third Wave anymore, it’s a Boston company [Hologic], and EraGen is now a Texas company [Luminex]. And so I always worry that we do a great job of creating businesses but we don’t do a great job of maintaining [our] position here in the state of Wisconsin.”
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