Provenge, Provenge, Provenge. The drug for prostate cancer, which is attempting to be the first approved treatment of its kind in the U.S. to actively stimulate the immune system to fight tumors, is the one product candidate shareholders love to obsess about from Dendreon. But behind the scenes, Seattle-based Dendreon (NASDAQ:DNDN) is making headway on another product in its pipeline that could keep the ship afloat if Provenge flames out next year.
Dendreon’s program to hit the trp-p8 target made its debut in public six years ago, when then-chief business officer (and future CEO) Mitchell Gold cut a deal with Genentech to co-develop cancer drugs that hit this target. Genentech agreed to pay $1 million upfront and buy $2 million of Dendreon stock, but neither company has said much more than a peep about this contender since. Last week I got an update on this program, and how it fits into Dendreon’s strategy, from chief scientist David Urdal.
“We are best known for our active immunotherapy, but I think of us principally as an oncology company which happens to have a lead program with immunotherapy,” Urdal says. “Companies tend to be defined by their lead program.”
There’s good reason for that, because for years Dendreon has funneled the vast majority of its resources into its lead program. But it plans to move a completely different kind of anti-cancer drug—a conventional oral pill—into its first clinical trial early next year. This drug, called D-3263, is designed to stimulate the trp-p8 protein target inside and on the surface of cells. Hitting this target might allow greater amounts of calcium, magnesium, and other ions to flow into cells, triggering a process called apoptosis, or programmed cell death. Dendreon presented some data at a medical meeting in Switzerland last month which showed it could shrink tumors in animals.
Dendreon has been excited about this target for years, ever since its scientists discovered the gene for trp-p8 in the late 1990s and received a patent for it, Urdal says. Basic lab studies have revealed that this protein is found on 100 percent of prostate cancer cells, about 93 percent of colon tumor cells, and 80 percent of lung cancer cells, Dendreon has said. The target is also found on healthy nerve cells that control cold sensations people feel, say, when they reach into the freezer to get a pint of ice cream, Urdal says.
Through the collaboration, Genentech scientists worked on genetically engineered antibody drugs to hit the target. That effort has run into “challenges,” Urdal says. That’s because antibodies are much better suited to hit targets on the surface of cells, and trp-p8 is mainly expressed inside cells, where small-molecule blockers are a better choice. Genentech declined its option to collaborate further on the small-molecule program, but retains rights to develop antibodies, Urdal says.
One reason Dendreon is forging ahead with the D-3263 program on its own is that it doesn’t take a lot of resources. Small-molecule chemicals are cheap to manufacture, and can be made by contractors to the company, Urdal says. Dendreon has also considered advancing its second immunotherapy candidate, lapuleucel-T (Neuvenge) for breast cancer, but that uses the same manufacturing process as Provenge, which is already taking up the company’s full capacity, he says.
The plan for D-3263 is enroll about 40 patients with any type of solid tumor, to get a read on safety, absorption, and metabolism of the drug at a variety of doses, Urdal says. It will be the only cancer treatment in clinical trials designed to hit the trp-p8 target, although other drugs that stimulate flow of ions into cells are proven to work for conditions like high-blood pressure. After a few months, the company will have some idea if D-3263 provides a viable fallback plan, which the company might need by the middle of 2009, when final results will show whether sipuleucel-T (Provenge) can actually extend patients’ lives with minimal side effects, as an earlier study suggested.
Urdal agreed that D-3263 “has that effect,” of being a fallback plan, although he says that isn’t the reason it’s moving ahead. “This is exciting to me,” Urdal says. “I get excited with any new investigational new drug application, particularly if it’s against a novel target.” He adds, “This gives us more shots on goal, which should increase the value of the company for shareholders.”