Anavo Therapeutics launches to drug phosphatases

Anavo Therapeutics has launched with about $24 million in seed financing to discover small molecules that target phosphatases—enzymes that remove phosphate groups from proteins. The Dutch start-up was cofounded by Birgit Zech and Gerhard Müller, a duo who previously cofounded the epitranscriptomics company Gotham Therapeutics.

Unlike kinases, which are enzymes that add phosphate groups to proteins, phosphatases have been historically hard to drug. While more than 60 kinase inhibitors have been approved in the US, there are no commercial drugs that target phosphatases. “We are trying to change that,” says Zech, Anavo’s CEO.

Phosphatases are linked to cancer, immune diseases, inflammation, and metabolic disorders, says Müller, Anavo’s chief scientific officer. Past attempts to target binding sites on phosphatases led to charged compounds that made poor drugs since they didn’t get into cells easily and bound to their targets in unspecific ways. “The entire industry dropped the field 20 years ago,” he says.

The recent trend of developing compounds that target allosteric sites on enzymes, rather than active sites, is leading to a new wave of phosphatase drug discovery programs, most notably an inhibitor of the phosphatase SHP2 being developed by Novartis, Müller says. One of Anavo’s strategies is to exclude molecules in its screens that are predicted to bind phosphatase active sites, he adds.

Anavo won’t disclose which phosphatases it is targeting, but its initial interest is in cancer, Zech says. The firm is looking for allosteric modulators that can either stabilize and reactivate phosphatases that have been turned off in cancer cells or that can inhibit phosphatases whose errant activity is linked to cancer growth.

The company has recruited phosphatase experts Mathieu Bollen of the University of Leuven and Nicholas Tonks of Cold Spring Harbor Laboratory to its scientific advisory board.