1:38 PM
Feb 23, 2017
 |  BC Innovations  |  Tools & Techniques

Showdown: bacteria vs. virus

Could bacteriophages solve the antibiotic resistance problem?

Drug developers are starting to revisit bacteriophages as a solution for two of the biggest questions in translational research: how to treat resistant bacterial infections, and how to manipulate the human microbiome. A spate of small companies is leading the way, using new technology to resuscitate a dormant modality.

Bacteriophages were largely abandoned by the industry decades ago in favor of broadly acting small molecule antibiotics. The agents, also known as "phages," are viruses that infect and destroy bacteria, acting as natural predators for the microbes.

Unlike small molecule antibiotics, which target broad classes of bacteria, each phage is highly specific for an individual species or even strain of bacteria.

But small molecule antibiotics supplanted phages in the middle of the last century because their broad-spectrum activity was seen as a major advantage, and limitations on diagnostic technologies made it hard to match a phage to a specific infection. Moreover, small molecules had much easier CMC.

"With the modern era of antibiotics, we had drugs with a broader spectrum of activity that could be manufactured and transported pretty easily, so phage therapy fell by the wayside, especially in the West," said Jeffrey Wagner, chairman and CEO of EnBiotix Inc.

EnBiotix is one of a crop of companies that recently raised money or moved into the space. The company raised an undisclosed series A round last year, joining newco EpiBiome Inc., a graduate of Johnson & Johnson’s JLABS incubator that raised $6 million in a series A round last year and subsequent undisclosed additional funding. Intralytix Inc., which initially focused on non-therapeutic applications, announced a deal with Ferring Pharmaceuticals A/S to develop phage-based therapies in 2015.

One public company, AmpliPhi Biosciences Corp., moved into phages with the 2011 purchase of Biocontrol Ltd., followed by three more deals. Since 2013, it has raised $47 million in five offerings, including $4 million in a follow-on last November. Earlier today, AmpliPhi announced Massachusetts Institute of Technology (MIT) associate professor Timothy Lu, a pioneer in bacteriophage engineering, as the chair of its SAB.

The revived interest is largely a response to the rise of antibiotic resistance, and is partly rooted in the fact that phages have continued to be used in Russia and former Eastern bloc countries.

Alexander Sulakvelidze, VP of R&D and chief scientist at Intralytix, told BioCentury that his company saw an opportunity to re-introduce phages in the West to solve the antibiotic resistance problem.

"In developing countries, drug-resistant bacterial infections can be treated with bacteriophages, but phages are not yet therapeutically utilized in the United States. It just didn't make sense to me that patients in the U.S. were dying of resistant bacterial infections when a potential treatment was readily available overseas," he told BioCentury.

According to Sulakvelidze, phages are re-emerging now for three reasons: their high specificity for individual bacterial species and strains, including antibiotic-resistant bugs; their ability to penetrate biofilms that shield bacteria from many traditional antibiotics; and their ability to protect the gut microbiome, which is often disrupted by standard antibiotics.

He added that advances in orthogonal fields have paved the way, and the environment is now primed for the technology. "The diagnostic methodology has dramatically evolved so we can quickly and accurately identify the specific cause of an infection," making the use of highly...

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