Novophage Forming to Combat Antibiotic Resistance with Engineered Viruses

3/5/09

A group of biotech veterans and up-and-comers in the Boston area are forming a startup called Novophage to make engineered viruses that may help combat the growing problem of resistance to antibiotics.

It’s early days for Novophage. The firm has no office or venture backers to speak of, but it has formed an impressive roster of scientific co-founders that includes MIT’s prolific biotech inventor Bob Langer, Boston University bioengineering professor James Collins, and MIT chemical engineering professor Gregory Stephanopoulos. Research related to the firm’s science—led by co-founder Timothy Lu, a student at Harvard Medical School—was due to be published this week in the online version of the Proceedings of the National Academy of Sciences. I got the inside scoop on this company’s strategy from Lu and Collins yesterday.

Novophage’s engineered viruses have shown the potential to be used in combination with traditional antibiotics, offering what could be a new way kill bugs that have developed resistance, Lu says. This combination strategy offers an alternative to developing new stand-alone antibiotics, which have been slow to reach the market the past couple of years. For example, the FDA late last year shot down Cambridge, MA-based biotech firm Targanta Therapeutics’ bid to garner approval of an antibiotic called oritavancin for complex skin and skin-related infections caused by antibiotic-resistant bacteria. Another contender, South San Francisco-based Theravance, has also been delayed by regulatory hang-ups.

“We wouldn’t have to worry about antibiotic resistant bacteria if there were a lot of new antibiotics coming out from the pharmaceutical industry,” Lu says. “Our technology provides the ability to extend the useful lifetime of antibiotics and to solve the growing antibiotic-resistance problem.”

Lu and his fellow researchers have engineered bacterial viruses, called bacteriophages or phages, to strike at the natural DNA repair mechanism in bacteria that helps them resist antibiotics. To accomplish this, BU’s Collins explained to me, the phages serve as Trojan Horses that infect bacteria and cause increased production of proteins that disrupt the repair genes and enhance the affects of traditional antibiotics. (A picture is worth a thousand words, so here’s a link to an animated demonstration of how the phages work.)

The most notorious of several resistant bugs, called MRSA, infected some 94,000 Americans and killed about 19,000 people in the U.S. in 2005, according to the Centers for Disease Control and Prevention. The infections occurred mostly in hospitals.

“Given the growing prevalence of antibiotic resistance,” Collins says, “we are in substantial need for new means to go after these bugs.”

Novophage is in the early stages of developing a strategy for commercializing the engineered viruses developed by Lu, Collins, and others. The founders of the startup are now working the local business plan circuit—including the BU $50K Business Plan Competition, the Harvard Business School Business Plan Contest, and the MIT $100K Entrepreneurship Competition. Novophage hasn’t begun to make its pitch to venture investors, Lu says, but he believes that the science has advanced to a point where the founders are ready to begin such discussions.

The founders were encouraged by the results of their recently published mouse study, in which they tested their phages in combination with three classes of antibiotics known as quinolones, beta-lactams, and aminoglyclosides. Eighty percent of infected mice were cured when receiving antibiotics and the engineered phages, compared with only 20 percent that survived after taking antibiotics alone. (Lu, who earned his doctorate in bioengineering from MIT, won the 2008 Lemelson-MIT Student Prize for his research of engineered phages that can attack bacterial films that form around implantable medical devices and can cause infections.)

The idea of using phages to treat infections is not new. Intralytix, a Baltimore-based biotech firm developing phages harvested from natural sources, says that phages were first used to treat infections in the early 1900s. However, the Novophage founders believe their engineered phages will be more potent than natural phages.

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  • Jennifer

    Ryan,
    I thought it interesting that you used Targanta as an example of a traditional antibiotic company. Funnily enough – it started out as an antibiotic target discovery company called Phagetech! The field has come full circle.