Aeglea Biotherapeutics raises $44 million to develop arginine deprivation therapy

Aeglea Biotherapeutics raised $44 million in Series B financing led by Lilly Ventures and Novartis Venture Fund. The company, founded in 2013, is developing engineered enzymes that degrade specific amino acids in the bloodstream.

Aeglea’s lead drug candidate, AEB1102, is an engineered version of arginase. The company uses AEB1102 as an enzyme replacement to treat hyperargininemia that results from a mutation in the arginase gene.

Aeglea has greater ambition. They believe the drug has potential in cancer. The rationale is that normal cells can make their own supply of arginine in a three-step biosynthesis, while tumor cells must obtain arginine from the bloodstream.

Arginine deprivation therapy is not a new idea. Arginine can be degraded by three enzymes: arginase, arginine decarboxylase, and arginine deiminase. Taiwan-based Polaris Group is testing its pegylated arginine deiminase, ADI-PEG 20, in liver cancer in a Phase III trial.

To be honest, I have no confidence in arginine deprivation therapy. In the Phase II trials of ADI-PEG 20 in liver cancer and melanoma, no objective responses were seen[1,2].

The efficacy of arginine deprivation therapy depends on the degree of arginine-dependency of cancer cells. Aeglea needs a companion diagnostic to identify patients whose tumor cells are dependent on exogenous arginine. AEB1102 will enter Phase I trials in solid tumors in 2015H2.

[1] Br J Cancer. 2010, 103(7), 954-960.
[2] Invest New Drugs. 2013, 31(2), 425-434.

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