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known as Fibroblast Growth Factors (FGF). These proteins are thought to play a role in the growth of tumors, and the formation of blood vessels that tumors use to grow and thrive. While multi-billion dollar biotech franchises have been built on inhibiting other protein targets that perform functions like this—Genentech’s bevacizumab (Avastin) against VEGF, for one—no one has developed a FDA-approved cancer drug against FGF. Five Prime, which owns 100 percent of the rights to this molecule, believes it is has the only protein drug against this class of target in the clinic, Knickerbocker says.
“We are actively partnering 1039 now, and it has garnered significant interest,” he says.
Data is still preliminary on whether this drug has a real future as a cancer drug. The company is almost finished with a Phase I clinical trial, in which it is testing an escalating series of doses to assess safety. Five Prime is still keeping its options open, testing the molecule against a variety of solid tumors, including those from the prostate, lungs, uterus, kidney, brain, and liver. But interestingly, the company is looking for biomarkers in the very early days of development, to find patients who have aberrations in FGF pathway signaling, who might be more likely to respond to the Five Prime drug. If that hypothesis pans out, then FP-1039 could be following the template of another drug that is built on a companion diagnostic test—Genentech’s trastuzumab (Herceptin) for women with forms of breast cancer that overexpress the HER2 growth protein.
“We think biomarkers will play an important role in development of this drug in Phase II,” Gregory says.
Other companies have developed antibody drugs against the same target as Five Prime, the FGF receptor 1, but quit developing them after they saw too much toxicity—particularly a sudden weight loss in animals. The reason for this effect with antibodies isn’t fully understood, Knickerbocker says. Conventional small molecule compounds have been made against the FGF receptors, but they tend not to be as selective for the target, and cause toxicities. But with a genetically engineered protein, Five Prime hasn’t seen that sort of off-target toxicity in its first study, he says.
Part of what makes the FGF protein so interesting, other than the scarcity of drugs like it, is that it might be part of a combination drug strategy against cancer. That’s because patients might respond for a while to an existing drug targeted against a protein like VEGF, but the cancer eventually finds a way to spread anyway through other growth mechanisms. So as long as the Five Prime drug has a clean safety profile, or doesn’t exacerbate any side effects from the other drugs, it could be part of a multiple targeted drug approach. “The greatest potential is in combination with chemotherapy or other targeted therapies,” Knickerbocker says.
Of course, with a scientific engine that has produced 4,500 other secreted proteins in a library, Five Prime has other drug candidates of its own, and others it is developing with partners, marching their way on the long slog toward clinical trials. If any of them show promise, or show promise and then flame out, they can be stories for another day. For now, Five Prime is trying to show it can mature from a pure science platform into a real drug developer based on a scientific platform.
Once one or two of its drugs starts amassing some solid evidence from clinical trials, then things could get a lot more interesting.
“A platform strategy in biologics is highly competitive. It’s also becoming scarce. Most major biologic companies have been acquired,” Gregory says. “With a protein library like this that no one else has, we’re putting ourselves into a position of very strong competition.” To use a colorful analogy, she put it this way: “We’re like a shiny submarine, right under the surface. All the Big Pharma companies can see it coming.”
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