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12:00 AM
Apr 28, 2014
 |  BioCentury  |  Emerging Company Profile

Aeglea: Old enzymes, new tricks

Aeglea's engineered human enzymes starve tumors

Aeglea BioTherapeutics Holdings LLC is developing enzymes to starve tumors that depend on outside sources of specific amino acids. Aeglea's engineered human enzymes may offer lower immunogenicity and greater activity than natural versions further along in development.

Since the 1990s, clinicians have used asparaginase enzymes to treat acute lymphoblastic leukemia (ALL). For reasons not yet understood, ALL cells tend to lose their ability to make asparagine.

Asparaginase starves tumor cells of asparagine by converting it into aspartic acid. Normal cells are unaffected because they can synthesize asparagine.

However, only a handful of similar therapies have followed this strategy because humans lack suitable enzymes and microbial ones may trigger anaphylaxis or neutralizing antibodies, even when pegylated.

Aeglea hopes to overcome those issues with a trio of human-derived enzymes engineered for stability and new specificity.

CEO David Lowe said redesigning the enzymes required no technological breakthrough, just good knowledge of enzymology.

"There are no human enzymes with the right substrate specificity or biochemical properties to be suitable as direct product candidates," he said.

The enzymes came from the laboratory of...

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