“It’s the story of the frog in the frying pan,” Entasis Therapeutics CEO Manos Perros told Business Insider this week when we sat down with him to learn more about his company, which is working on drugs to treat more nefarious strains of drug-resistant bacteria.
As the expression goes, if you put a frog onto a hot frying pan it will jump right back out. But if you put the frog on the pan with the heat on low and gradually increase it, the frog will stay put and meet its demise.
That gradual heating is what’s happening with antibiotic resistance, or the phenomenon that is occurring as the bacteria we’ve been tackling with powerful drugs grow increasingly resistant to them, said Perros.
Perros is far from alone in his convictions — Centres for Disease Control and Prevention director Tom Frieden made headlines in 2013 when he proclaimed that the US would “soon be in a post-antibiotic era,” meaning we’d be plagued by everyday infections that our drugs could no longer handle. Last year, newborns in India were dying at alarming rates from infections that were once curable, and 23,000 Americans died in 2013 from bacterial infections that didn’t respond to antibiotics.
Entasis wants to stop antibiotic resistance by making more precise and effective antibiotics for multi-drug resistant bacteria. And Synthetic Biologics wants to do it by keeping our gut bacteria healthy in the first place.
More precise drugs
After about ten years of developing an antibiotic to treat multi-drug resistant gonorrhea, AstraZeneca decided to spin out its antibiotics division in March 2015 as Entasis. The pharma giant gave Entasis $40 million in seed funding, and Perros said they’re in the process of raising their next round. “It was like giving birth to a teenager,” he said, of developing a drug that’s already in clinical trials.
At a time when medicine is slowly becoming more precise in areas like cancer and genomics, tackling antibiotic resistance isn’t seen as the coolest place to be, says Perros.
“Nobody wants to be in backwater areas like antibacterials when you can be in sexy areas like immuno-oncology,” Perros said, referring to a hot new area of cancer treatment that many drug companies and investors are diving into recently.
But his company is commited anyway, because antibiotic resistance is not a problem that’s going away anytime soon.
However, when it comes stopping antibiotic resistance overall, Perros said there needs to be a lot more research in to develop our understanding of bacteria on the molecular level. “There needs to be more fundamental work, including better understanding how bacteria work in the same way we spent two decades learning how cancer cells work so we could better target them.”
Entasis’ drugs target types of bacteria with an extra layer of protective casing that makes them more resistant to antibiotics. Their treatments are designed to squeeze past that extra wall of defence and stay in the bacteria, where they can do their job.
None of which is to say their drug won’t eventually develop resistance as well. Perros is sure it will. “If you meet anyone who tells you we have this great antibacterial, no resistance will develop to it, they’re wrong.”
Instead, the goal here, says Perros, is to make sure the drug is only used in the most extreme settings so that they can at least slow down the rate at which resistance builds.
More protected guts
One of the other big problems with antibiotics is that they wipe out the thriving communities of good bacteria in our gut. And as we struggle create more and more powerful antibiotics to overcome the increasingly powerful bacteria, their impact on our guts is getting worse.
Synthetic Biologics is trying to tackle the superbug problem from this angle — by breaking down antibiotics before they hit the gut.
They created a pill made out of proteins. Patients who are taking antibiotics take the pill while they’re on the other drugs. The pill gets activated between the intestine and the gallbladder, which provides the bile that breaks down your food.
Like any other protein you ingest, Synthetic Biologic’s pill, which is currently in phase 2 clinical trials, gets absorbed and broken down, CEO Jeffrey Riley told Business Insider.
The hope of the pill is to let your gut bacteria blossom and prevent an environment that makes bacteria get even stronger.
“If you’re not setting up that artificial environment where the strong survive and the weak die, guess what you get rid of? Antibiotic resistance,” Riley said.
In other words, perhaps frog might have a chance of jumping out of that steaming hot pan after all.
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