punch holes in the cells, and kill them with a single strike. Part of what’s interesting is that these drugs can be made to bind to target “virulence factors”—molecules that the pathogen needs to cause disease. So if the bacterium finds a way to mutate to resist the new drug, it won’t cause any harm, because it won’t be virulent.
AvidBiotics first started developing its specific C. diff compound, which it calls Diffocin, as part of a collaboration with Lexington, MA-based Cubist Pharmaceuticals (NASDAQ: [[ticker:CBST]]). Martin, a former board member of Cubist, said AvidBiotics got the drug back after the program missed an early milestone. But in the last two years, AvidBiotics has gained confidence in the program after showing its potency against 40 different clinical strains of C. diff in the petri dish, while also seeing it doesn’t kill related forms of Clostridium bacteria, Martin says. AvidBiotics doesn’t yet have data to show the drug can kill C. diff in animals, and finding good animal models for this disease can be difficult. But the company has done rabbit experiments which show it can give a similar protein orally, and that researchers see in rabbit feces that the AvidBiotics drug was able to kill the desired bacteria, Martin says.
The movement toward more precisely targeted antibiotics is still in its early days. But Martin says fast/cheap new DNA sequencing technologies are making it possible to ask all kinds of new questions about these bugs that co-exist with humans. As scientists learn more and more about the “microbiome,” Martin says he expects it will lead to increasing interest in narrow-spectrum antibiotics that will take out an individual bad actor, while sparing the good bacteria. This might seem odd to big pharma companies—at least those still pursuing antibiotics—because they have traditionally sought out “one-size-fits-all” antibiotics with blockbuster sales potential, just like they once did with cancer drugs. But that’s changing as scientists develop greater understanding of the molecular basis of cancer. Just as big companies are beginning to understand the potential of personalized cancer treatment—like Pfizer’s crizotinib (Xalkori)—they may one day appreciate the power of targeted antibiotics.
“As we’ve seen with cancer, if you have a really good diagnostic, and a lot of information in your quiver, you can pull out an arrow that hits that mutation,” Martin says. “The same thing will happen in antibiotics.”
