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EnBiotix Inc.: Antibiotic Helpers for Resistant, Persistent Bugs

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By Anette Breindl
Science Editor

It may be a bad environment for early stage deals for most companies. But not for start-up EnBiotix Inc., according to its CEO Jeffrey Wager.

The company, which was founded in 2012, is "in discussions with multiple pharma companies" for partnering opportunities.

The reason, Wager told BioWorld Today, lies in the company's approach. EnBiotix is not trying to develop standalone antibiotics. Instead, its technologies "could be potentiating a significant proportion of the antibiotics that are currently out there."

Such helpmates are certainly needed. Increases in drug-resistant infections and the spread of such bugs from hospitals to communities have not, in recent decades, been matched by the development of novel antibiotics and antifungals. As a result, infections that were once terrifying, and then routine, are coming full circle to be once more untreatable.

The idea that the war between drugs and bugs can be shifted by giving the former a boost is not new. Wager pointed to antibiotics such as Augmentin (GlaxoSmithKline plc) that combine penicillins with beta-lactamase inhibitors. Bacteria can develop resistance against penicillins by producing beta-lactamase, and adding the inhibitor can give them a second lease on life.

"Our product concept takes that example," Wager said. "But it extends and broadens it by being applicable to all major classes of antibiotics."

EnBiotix, whose name is meant to evoke the phrase "engineered antibiotics," is a start-up out of Boston University that aims to commercialize findings out of the laboratory of co-founder James Collins. Other co-founders include Apeiron Partners LLC, where Wager is a founder and managing director. Apeiron is a full-fledged investment bank in terms of its licenses, but in practice specializes in a few select areas, among them university spinouts and "select" new company formations such as EnBiotix, Wager said.

EnBiotix is in the process of licensing about half a dozen technology platforms out of Collins' laboratory whose overarching goal is to give existing antibiotics a boost in their fight against bacteria and fungi.

Collins and his team published data on one of their approaches in the Jan. 6, 2013, issue of Nature Biotechnology, where they described using a bioinformatics approach to look for metabolic genes that would boost the production of reactive oxygen species (ROS) in bacteria.

ROS are usually considered bad for cells, including bacteria. Previous work by Collins has shown that the situation is more complex. "Bugs use this stress response partly as escape strategy," Collins told BioWorld Today, developing resistance through an enhanced mutation rate caused by higher levels of ROS. (See BioWorld Today, Feb. 19, 2010.)

Nevertheless, his team also showed that the cell killing abilities of antibiotics were enhanced when the drugs were combined with compounds that could block bacteria from getting rid of ROS.

"In our new work, we wanted to see whether we could shift the other goalpost" by inducing bacteria to produce more ROS, Collins said.

His team began by using bioinformatics to identify more than 100 metabolic reactions in cells that can change ROS levels. "Many of these reactions," he said, "are not accounted for in typical genome scans," and their sheer number has led him to suspect that looking at ROS in greater detail would show that it is an important player in cell metabolism.

The team then validated some of the predicted targets by showing they could be used to manipulate ROS production, and that bacteria that produced higher levels of ROS were more susceptible to several major classes of antibiotics.

Putting a finger on the scale by targeting ROS production is one of the strategies that EnBiotix plans to pursue, but not its most advanced program. That distinction goes to the company's antipersisters platform.

Persistent infections are those that survive treatment with antibiotics to come back. Persistent lung infections are what ultimately kill many cystic fibrosis patients.

EnBiotix is developing a new treatment for such lung infections, which consists, Wager said, of "a marketed antibiotic with a marketed second agent" to enhance the antibiotics' killer instincts. Combining them both in a new formulation and delivery system, he added, would bring the product back under patent protection. EnBiotix hopes to be in the clinic testing that particular product within 12 months to 24 months.