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Solomon discusses new ways that researchers are fighting against bacterial resistance to medications.
Jonathan Solomon, CEO of BiomX, spoke with Pharmaceutical Executive about his company’s work developing natural and engineered phage cocktails. One of the benefits of these cocktails, he explains, is their ability to fight back against antimicrobial resistance.
Pharmaceutical Executive: How big of a problem is antimicrobial resistance?
Jonathan Solomon: It's a huge problem. We're talking about a number of deaths that is starting to exceed many common pathogens. It's a growing problem, and it just gets bigger and bigger due to extensive antibiotic usage, which got even worse during the COVID-19 pandemic. As we began to address the problem, we analyzed the market and we found this to be a really interesting opportunity. We looked at patients who have an average genetic mutation that hurts many of their organs. They have problems in their lungs, liver, gut, et cetera, so they basically get treated with antibiotics as they grow up. This is a patient population which is taking antibiotics all the time. Basically, these guys are out of options now, although the field has changed a lot with the introduction of new treatments. If one of these patients had a life expectancy of 30 years, it's now 50 or more in some cases. It has changed dramatically, but we're still not offering an alternative to take out these antibiotic resistant bugs. Often, these patients deteriorate and as a last resort, they’ll get a lung transplant. It's such a complicated and difficult surgery and there’s the chance that a drug-resistant bug could reemerge in one of these patients and just take over the body. We're looking at antibiotic resistance through a straw, and we're looking at a very specific patient population.
PE: Would you be able to go into detail about your recent success treating cystic fibrosis using phage cocktails?
Solomon: We did a small study of nine patients. Two patients were on a placebo and seven were on the treatment. The patients were treated for seven days: they got their first dose on the first day, they got they got placebo on the second day, a low dose on the third day, then a high dose, and then they got four consecutive days of twice a day high dose treatment. That was supposed to be a safety study with a very low dose, so we had low expectations. What we saw was, on average, we had a 1.4 log reduction in these patients after only a few days of dosing. For us, it's extremely encouraging, because we can say phage has this clear advantage.
There's another advantage that we haven't talked about, but bacteria are very sophisticated. They can defend themselves as a single bacteria cell, but there are a lot more sophisticated bacteria that can think and can actually defend themselves as a community. They know to communicate and collaborate with one another and one of the things they do is produce something called a biofilm. When a bacteria colony forms, they can start talking to one another and say, “hey, this looks like a great place to build our own city.” They start producing a sticky mixture of proteins and carbohydrate that provides mechanical adhesion to surfaces. You see these long areas of patients that are full of biofilm, but it's also like a big wall, as in that it protects them from external assaults such as antibiotics. Basically, when patients don't respond to antibiotics it could either be because the bacteria at the single material level have produced mechanisms against antibiotic resistance, or that they have produced a biofilm and the antibiotics are not penetrating. Because phage and bacteria have been battling it out for billions of years, some phage have an antibiotic capability. If you're sophisticated enough, you can find the phage in nature that have evolved to have antibody film capabilities and add them to your product. That's going to the two prime advantages. I'm telling you all this because we're trying to get the word out.