News Column

James Prudent: Leading Centrose toward a new type of cancer-fighting drug

August 3, 2014

By Judy Newman, The Wisconsin State Journal

Aug. 03--Centrose is developing a new type of drug to fight cancer that won't make your hair fall out, won't make you nauseous and won't involve shots or pills, president and chief executive James Prudent says.

In fact, he says, if the Madison company's novel formulation is successful, it could revolutionize the way all sorts of drugs are made.

Prudent, 50, grew up in Milwaukee and liked the outdoors so much he thought he might be a forest ranger, at one point. Instead, he turned to biotechnology, earning a bachelor's degree in bacteriology and medical microbiology from UW-Madison and a doctorate in chemistry from the University of California-Berkeley.

A veteran of two other Madison biotechs, Prudent was one of the inventors of Third Wave Technologies' Invader technology for detecting specific genetic sequences. Third Wave is now part of Hologic, of Bedford, Massachusetts. He was also chief scientific officer of EraGen Biosciences, acquired by Luminex, of Austin, Texas, in 2011, before co-founding and taking the helm at Centrose in 2007.

Prudent is married and the father of three children, ages 11-17, and gets his taste of the outdoors now by hunting and fishing in Wisconsin.

Q: When Centrose was founded in 2007, it was based on technology from the renowned Memorial Sloan Kettering Cancer Center in New York, using sugar molecules. It was a coup to bring not only the technology but Jon Thorson, the researcher who developed it, to the UW-Madison. Now, though, Centrose has changed its course and Thorson is no longer here. What happened?

A: Jon Thorson had developed a process that allowed us to screen a number of different small molecule drugs for enhancement with sugar molecules. You can put sugars on molecules to enhance their activity, for example, to keep a drug in the patient's system longer or to clear it out of the system faster. It's called glycochemistry.

Initially, we were using that to develop drugs. But our direction changed pretty quickly when, in a side project, we discovered we could use sugars to attach molecules to proteins and use those proteins to direct the molecules to diseased cells.

We're taking antibodies and putting a drug on them -- actually a hormone -- and directing that hormone to cancer cells. The type of hormone is called cardiac glycosides, basically steroids. The first time researchers realized this type of hormone is a potent anti-cancer cell was at the UW-Madison in 1964, with the discovery by Raymond Doskotch.

Q: Why didn't that become the basis for cancer treatment?

A: Because they kill every cell. That's what most chemotherapy cancer treatments do and that's why your hair falls out, you throw up and you look sicker than you did before the cancer.

Centrose uses a drug-targeting system we call extracellular drug conjugates. They work outside the cell. This is the first time any company has made a drug that doesn't have to get inside the cell. That makes it very, very potent -- you need only a small amount. We've tested them in primates and have shown they're very safe.

We use a class of steroids that's made naturally in the body, particularly at times when cells are rapidly growing. The thought is that these cardiac glycosides control unwanted cell growth. In the U.S., there is a cardiac glycoside that's prescribed on a daily basis for heart disease: digitoxin. Studies have found that people who take digitoxin have less of a chance of developing cancer.

Our molecule is very closely related to digitoxin. We found a way to attach it to antibodies so that when it binds to the targeted cells, the glycoside is still active. This has never been done before with any molecule. In the past, scientists could put a drug onto an antibody but it has to be broken down by the body to be effective. That's a time-consuming process and it has toxic effects on all cells. Our compounds don't require breakdown, maintaining their targets to the cancer cells.

We have a lot of firsts going on at Centrose, and they are leading to a lot of interesting science.

Q: Centrose is also set up differently from the traditional way, where a company handles the entire drug-development process on its own. Tell us about that.

A: Centrose is based in Madison and all of the research and development and intellectual property are here at our labs and offices at 918 Deming Way, on the far West Side. We use contract research organizations and contract manufacturing organizations to make the products and conduct the tests.

Catalent, 726 Heartland Trail, makes our antibodies and they have a whole factory that we could never create. We've made them here, but to scale up and manufacture products under what's called "good manufacturing practices," we outsource that. It saves a lot of money.

Seattle Genetics, a drug-development company whose shares are sold on the Nasdaq market, works in a similar way.

Q: What are Centrose's lead products?

A: Our first drug is EDC1 and is aimed at late-stage metastatic cancers, which means the disease has spread. We licensed the first antibody from the National Cancer Agency in Tokyo. They immunized mice with human cancer cells to make the antibodies that we use. Our compound is really active on pancreatic cancer and seems to be on lymphoma, too. Acute myeloid leukemia is one of our targets; it is one of the hardest leukemias to treat. The drug may also be used to treat cystic fibrosis.

EDC2 deals with head and neck cancers, especially where previous treatments have failed.

EDC8 is getting big excitement now; it is really active on various leukemias. Six companies are making products for it, and we are working with a researcher in Italy on this.

All three products are in tests with animals but none has started human trials, yet. We use monkeys because mice are horrible models for targeted therapies. They don't have the same proteins or immune system and they don't live as long. Mice are completely immune to cardiac glycoside drugs. So we use monkeys -- they're the only animals that will give the safety profile the Food and Drug Administration wants to see. We don't give the monkeys cancer, but we give them escalating doses of the drug to see how they react to it.

We were very pleased to find out that even though these animals are just as sensitive to these steroids as humans are, the drugs don't seem to cause serious side effects, like in standard chemotherapy. We don't see heart or neurological problems, either.

Q: It costs a lot to go through the development and testing stages of a new drug, doesn't it?

A: About $15 million to do all the work before each drug gets into human trials. When you start the human trials, phase one, the safety test, costs $5 million. That's what we're trying to get to. If the compound does well there, your company suddenly gets recognized. Then two more sets of human trials are needed to see if the drug is effective and determine what the dose should be. That costs many millions more.

Q: How will these drugs be administered?

A: They won't be a pill, and they won't be a shot or an intravenous tube. A lot of these will be based on patches, where the drug dissolves through the skin.

Q: You mean these will be more effective drugs with fewer side effects and no needle or pill involved?

A: Yes.

Q: How much money has Centrose received up to now?

A: So far, a little over $8.5 million. About $3.5 million of that is from federal funding; the rest, from investors. We also set up partnerships to help pay for the manufacturing.

Q: So, if all goes well, how soon could any of Centrose's drugs be on the market?

A: It will probably be three to five years before any of them are available to patients.

___

(c)2014 The Wisconsin State Journal (Madison, Wis.)

Visit The Wisconsin State Journal (Madison, Wis.) at www.wisconsinstatejournal.com

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Source: Wisconsin State Journal (Madison, WI)


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