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Armata has joined together two seasoned drug development teams, AmpliPhi Biosciences and C3J Therapeutics, to tackle the global and increasingly serious threat of antimicrobial-resistant bacterial infections. Driven by rigorous and innovative science, Armata is developing high-impact, best-in-class bacteriophage therapeutics with the potential to save millions of lives.

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Bacteriophages

What are Bacteriophages?

Bacteriophages or phages are believed to be the most abundant and diverse life forms on Earth and the natural predator of bacteria. A lytic phage infects and rapidly kills a host bacterial cell, making copies of itself in the process. The newly produced phage progeny are then released into the surrounding environment, ready to attack and kill additional nearby target bacterial cells until they have been eliminated. When there are no target bacteria left for the phages to infect, the phages are removed through the body’s natural clearance processes. Since each strain of phage generally exploits only a particular bacterial host, phages hold the promise of delivering species-specific elimination of disease-causing bacteria while sparing non-targeted bacteria, such as those found in the beneficial microbiota.

A typical lytic phage amplification cycle takes around 30-60 minutes, and only stops once the pathogenic bacteria have been eliminated. The use of natural and synthetic phages has several advantages compared to traditional antibacterial therapies based on their unique mechanism of action:

step 1 - lytic cycle

1) Phage binds target bacteria.

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step 2 - lytic cycle

2) Injection of phage DNA, replication, and production of phage proteins.

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step 3 - lytic cycle

3) Phage assembly.

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step 4 - lytic cycle

4) Bacterial cell bursts, releasing progeny phages that then bind neighboring target bacteria.

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step 5 - lytic cycle

5) Cycle repeats. Reinfection results in an exponential increase in the number of lysed bacteria.

Read about some of the unique benefits of phages here »

Ability to Treat and Re-Sensitize Antibiotic-Resistant Bacteria

Phages kill bacteria through a different mechanism of action than traditional antibiotics and therefore phage therapeutics are unaffected by the increasing incidence of antibiotic resistance. Phages have also been shown to re-sensitize antibiotic-resistant bacteria to antibiotics to which they were previously insensitive.

Ability to Disrupt Biofilms

Biofilms are layers of aggregated bacteria and other extracellular components that shield and protect bacteria from antibiotics. These complex communities of bacteria can render conventional antibiotics almost completely ineffective. Killing bacteria in biofilms can require concentrations of antibiotics that are up to 1000X higher than normal. For patients, this can mean that bacterial infections involving biofilms aren’t treatable because such large doses of antibiotics could be toxic. By contrast, some phages are able to breach this defensive shield and produce a strong therapeutic effect by penetrating the biofilm and replicate locally, disrupting the biofilm and leaving the remaining bacteria exposed and vulnerable to additional phages, the patient’s immune system and available antibiotics.

Ability to Precisely Target Therapies

Phage therapies are highly specific to their target bacterial strains. They cannot kill mammalian cells and have minimal impact on beneficial bacteria.

Ability for Combination Therapies

Different phages can be combined to target more than one species of bacteria. Phages can also be used in combination with antibiotics, in some cases to achieve a bigger therapeutic effect than either alone.

Ability to Reduce Side Effects

Phage therapies have been administered to humans for nearly a century with few reports of serious side effects on their own. All antibiotics have side effects. Some of these, such as allergic reactions, are common and manageable. Other side effects are more debilitating, including antibiotic-associated diarrhea caused by infection with Clostridium difficile. If phages and antibiotics are used together, it may be possible to use lower doses of antibiotics and thus reduce the risk of antibiotic-related side effects.

Learn more about Bacteriophage Therapy here »