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Univ. Spin-Off Discovering New Antibiotics

Klebsiella pneumonia bacteria

Klebsiella pneumonia, a gram-negative bacteria (CDC.gov)

30 May 2017. A new enterprise founded by three microbiologists at Harvard Medical School is licensing the founders’ research to find treatments for antibiotic-resistant bacteria. The company, known as X-Biotix Therapeutics, is also a spin-off from the company X-Chem, both in Waltham, Massachusetts, and plans to adapt its drug discovery technology.

The founders of X-Biotix are Harvard Medical School microbiologists Thomas Bernhardt, Stephen Lory, and John Mekalanos, who started the company to find new treatments for the continuing problem of bacteria becoming resistant to current antibiotics. Centers for Disease Control and Prevention estimates that 2 million people become infected with bacteria resistant to antibiotics, leading directly to 23,000 deaths. The company plans to target gram-negative bacteria associated with conditions such as pneumonia, bloodstream infections, wound, and surgical site infections. “Gram” refers to a classification for bacteria where the microbes either retain (gram-positive) or shed (gram-negative) a test stain on their protective cell coatings.

Under the agreement, X-Biotix is licensing the researchers’ discoveries, including drug targets and testing methods, from their labs to find new molecular scaffolds or frameworks for antibiotics to block a wide range of gram-negative bacterial cells and their pathways. Bernhardt, Lory, and Mekalanos study biological mechanisms supporting development of cell envelopes and outflow of matter from bacteria related to antibiotic resistance. Financial aspects of the license agreement were not disclosed.

X-Chem is also giving X-Biotix access to its drug discovery technology to find new treatments for antibiotic-resistant bacterial infections. That technology identifies a library of small-molecule, or low molecular weight, compounds each connected to a unique DNA identifier. X-Chem first screens candidates to find those with an affinity for specified targets, then conducts DNA sequencing to highlight candidates that interact with as well as bind to the targets. The company says results from this process usually offer families or clusters of drug candidates with both the structure and chemical activity to advance into working drugs.

X-Chem says its drug discovery process is used to identify new compounds for a number of therapeutic targets, including some diseases considered difficult to treat. In December 2016, a paper in the Proceedings of the National Academy of Sciences describes the use of this process to identify drug candidates to inhibit protein targets associated with multidrug-resistant tuberculosis.

“The formation of X-Biotix,” says Rick Wagner CEO of X-Chem in an X-Biotix statement, “comes at a critical time in the industry, where the general void in antibiotic discovery efforts combined with the lack of specific efforts to discover and develop truly novel chemical scaffolds represents a challenge waiting to be addressed using a unique discovery approach.”

“Recent advances in understanding the pathways that bacteria use to build critical components of their cells,” adds Mekalanos, “have revealed novel vulnerabilities ready to exploit for antibiotic discovery.”

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