AvidBiotics Sees New Angle for Personalized Medicine in Antibiotics

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When you hear about personalized medicine, you might think first of the applications for cancer treatment, or maybe cystic fibrosis. But Dave Martin, the former head of R&D at Genentech, is thinking about personalized medicine in a whole new context—for antibiotics.

This concept, at South San Francisco-based AvidBiotics, is still at its earliest stages of development, and the company’s most promising antibiotic candidate probably won’t enter clinical trials until 2013, Martin says. But the program has potential to become a fascinating case study that nudges the healthcare system away from the reactionary, “one-size-fits-all” antibiotic prescribing habit that has led to problems with drug-resistant superbugs.

Here’s how AvidBiotics is thinking about taking on a dangerous bacteria called Clostridium difficile, or “C. diff.” About 3 percent of U.S. adults have C. diff in their guts already, and it usually co-exists just fine with all the other bacteria, causing no problems. But C. diff can become a problem if a patient comes to the hospital in a high-risk situation to get a certain form of surgery, cancer care, or maybe to spend time on a ventilator in the intensive-care unit. Knowing there’s a high risk these patients will get a virulent form of C. diff, the hospital can run a 45-minute diagnostic test from Sunnyvale, CA-based Cepheid to see if the patient is a carrier.

If so, the doctor could someday prescribe a targeted “narrow-spectrum” antibiotic from AvidBiotics that’s designed to kill the C. diff bug, and spare virtually all the normal, healthy bacteria in the gut. By using the drug in a preventive setting, doctors hope to stop the bug before it causes the nasty diarrhea that hospitals dread. An estimated 700,000 people a year are affected by C. diff, and the death rate is estimated at about 6 percent. By attempting to prevent the worst symptoms before they appear, a drug/diagnostic combo has potential to greatly reduce the number of long-term hospitalizations, which can easily cost the healthcare system more than $100,000 per episode.

“An ounce of prevention is really valuable in this disease. If we can prevent this disease in high-risk patients, rather than waiting until patients are very sick, then everybody wins,” Martin says.

This would represent an unusual approach to antibiotics. These drugs today are often prescribed after a patient gets sick. The doctor doesn’t know right away what bug caused it, and he or she has to wait a day or two for a lab culture to provide the answer. Rather than wait around for symptoms to get worse, the doctor often has to act quickly, prescribing a carpet bomb “broad spectrum” antibiotic that kills all kinds of bacteria, both bad and good. Researchers know that this indiscriminate killing of bugs in the gut interferes with the natural equilibrium, and creates problems for people’s immune systems, and nutrient absorption, that can linger for months, Martin says.

AvidBiotics isn’t the only company thinking about a prevention strategy with a narrow-spectrum antibiotic—San Diego-based Optimer Pharmaceuticals (NASDAQ: OPTR) is pursuing a similar strategy with its newly marketed product, fidaxomicin (Dificid). That company, which I reported on earlier this week, is studying its new FDA-approved antibiotic as a way to prevent C. diff infection in patients undergoing bone marrow transplants, where C. diff infections are known to increase the death rate, and cost an average of $130,000 per patient to treat. (Martin says the Optimer drug is an important advance, but he believes his company’s experimental drug is designed to more narrowly hit C. diff, while sparing other forms of bacteria.)

AvidBiotics, which I profiled here in September 2010, is using technology platform it licensed from UCLA to make engineered proteins that hit specific molecular targets on the surface of bacterial cells. These molecules, which the company calls Avidocins, are supposed to 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: 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.”

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