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.”
