Gate Bioscience launches to stop bad proteins at their source

Drug designers try many different tricks to degrade badly behaving proteins. Much of the action in that space comes from companies developing small molecules like proteolysis targeting chimeras (PROTACs), which degrade proteins that operate inside the cell. Gate Bioscience, a Versant Ventures–backed start-up that launched today with $60 million in series A funding, has set its sights on disease-causing proteins that are destined for outside the cell.

The company’s name hints at the mechanism behind their small molecules, which work within a channel in the cell’s rough endoplasmic reticulum. For many extracellular proteins, getting through this channel is an important step on their path to exit the cell. Gate’s molecules bind in the channel, preventing disease-causing proteins from escaping while allowing good proteins to move freely through. Unable to leave, the stymied proteins are then degraded, according to Gate cofounder and CEO Jordi Mata-Fink.

“We have something fundamentally new, which is the ability to selectively eliminate an extracellular protein with small molecules,” says Mata-Fink, a chemical engineer by training and a former principal at Flagship Pioneering. “And the way we do it is we go at them at their source, where they’re made.”

Recent years have seen some interest in drugs targeting extracellular proteins. In 2020, Lycia Therapeutics launched to pursue lysosome-targeting chimeras (LYTACs), which can grab proteins that are already outside the cell and hook them to a receptor that ferries the protein to the lysosome for disposal. Those molecules, which can contain an antibody, are sizeable. Gate’s molecules are small, meaning they can be taken orally and can access all tissues including the brain, according to Mata-Fink.