Prostate cancer has been one of the hot fields for new biotech drug development this year, and now Cambridge, MA-based Tokai Pharmaceuticals is getting into the game with a drug that it hopes will someday help men live longer and push the boundaries of science even further.
Tokai, which raised $22 million in May from Novartis Venture Funds and Apple Tree Partners, has been pretty quiet about what it is up to until today. The company is starting its first clinical trial in 50 patients to test the safety of—and look for some early signs of anti-tumor activity in— a once-daily oral pill it calls TOK-001. I heard about the concept of the drug and the company from R. Bruce Montgomery, a clinical investigator at the University of Washington, and Seth Harrison, the managing partner at Apple Tree, who’s serving as acting CEO of Tokai.
Tokai is getting into the prostate cancer field with a drug that it says is the only one of its kind to fight cancer cells simultaneously with three modes of action. The Tokai drug is building on some of the science that San Francisco-based Medivation has used to secure a partnership with Japan-based Astellas Pharma worth up to $655 million, and which prompted Johnson & Johnson to acquire Los Angeles-based Cougar Biotechnology for $894 million earlier this year. Using a completely different way of fighting tumors, by stimulating the immune system to fight cancer cells like a virus, Seattle-based Dendreon (NASDAQ: DNDN) showed it could extend lives of terminal prostate cancer patients by a median of four months time with minimal side effects, and its stock boomed nearly 10-fold this year. All of the companies have their sights set on treating a disease that kills about 30,000 men each year in the U.S.
“For the sake of people with prostate cancer, we really hope we have something,” says Tokai’s Harrison.
Scientists have known for decades that prostate cancer cells thrive on testosterone and one of its byproducts in the body, so standard treatment has long been focused on shutting down the production of tumor-fueling testosterone, Montgomery says. This treatment, known as chemical castration, usually works for about five to 10 years. But all men eventually develop resistance to the hormone-blocking therapy, Montgomery says.
Researchers have been trying to sleuth out how this can be, and it now appears that the cancer cells are clever at finding new ways to grow. Tokai is zeroing in on blocking three of the ways tumors use to grow, even when they are deprived of most of the usual testosterone they need.
One way is by blocking a receptor prostate cancer cells have for efficiently picking up trace amounts of the hormone. Another is by blocking an enzyme called CYP17 that allows the body to make small amounts of testosterone in adrenal glands, which can happen even while standard hormone-blocking drugs are essentially instructing the brain not to produce any testosterone, Montgomery says. The other way Tokai fights the cancer is by reducing the number of hormone receptors in prostate cancer tumors, essentially so they can’t vacuum up any testosterone in the body, Montgomery says.
One potential side effect to watch for will be if the drug turns off a lot of the normal ability of the adrenal system, Montgomery says. “What if you can’t make cortisol?” he asked, noting that would be a problem since cortisol is involved in the body’s natural response to stress and anxiety.
But there’s plenty of enthusiasm in the medical community for what Tokai is doing, Montgomery says. The Phase I/II clinical trial is being conducted at leading cancer centers like the University of Washington/Fred Hutchinson Cancer Research Center, the Sidney Kimmel Comprehensive Cancer Center, UCLA, Dana-Farber Cancer Institute, Roswell Park Cancer Institute, and others. “There’s excitement that this could be the beginning of what proves to be a very effective drug, perhaps the likes of which we haven’t seen before,” Montgomery says.
The technology for what became Tokai has its roots in the medicinal chemistry lab of Angela Brodie at the University of Maryland School of Medicine in Baltimore, says Tokai’s Harrison. Venture capitalists have been encouraged by the triple-threat mechanism of action of the company’s drug in animal tests, and they will hope to see at least a few anecdotal cases early on of the lower PSA scores that are a good sign that a patient is improving, Harrison says.
If all goes well, Tokai may have some preliminary evidence from its first clinical trial to present this June at the American Society of Clinical Oncology, Harrison says.
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