Matchpoint launches to advance covalent drug discovery

Matchpoint Therapeutics has publicly launched with $70 million in series A financing and an earlier $30 million in seed money to develop covalent drugs for immune diseases. Its founders include Stanford University chemical biologist Nathanael Gray and Harvard Medical School cell biologist Edward Chouchani.

Covalent drugs, once considered fringe players, have been gaining traction among drug developers for their ability to form long-lasting bonds with their protein targets. Unlike drugs that form reversible, noncovalent interactions, covalent compounds permanently shut down the disease-linked proteins they bind to, resulting in a potent therapy with a long action time. Selectivity is the name of the game to ensure that the compounds don’t stray to the wrong targets and cause side effects.

Matchpoint will initially pursue compounds that latch to cysteines on their protein targets. Cysteine is the most popular covalent docking site among amino acid residues for its strong nucleophilicity and low abundance in human proteins. The latter is a boon for selectivity, as low abundance narrows the available proteins for a covalent drug to tether to and hence the chances that it lands off-target.

The company says it uses a proprietary chemoproteomic and machine learning platform to identify druggable sites on disease-causing proteins. Matchpoint’s technology also predicts structural motifs of covalent drug candidates and evaluates their selectivity for target cysteines versus the rest of the proteins in the human body. For now, the company will focus on finding treatments for autoimmune diseases and inflammation.

“We are looking for novel binding modes and new binding opportunities on proteins that are well validated,” says Andre Turenne, Matchpoint’s CEO. “We have a high bar for the level of genetic or clinical validation for the targets that we’re going after.”

The company, based in Cambridge, Massachusetts, will use its start-up funds to advance multiple programs through the preclinical stage. It also plans to double its workforce to about 40 people by year-end.