Passkey aims to use single drugs for multiple proteins

A trio of biotech and pharma executives with backgrounds in computational chemistry and systems biology are making a bet: that new computational tools will allow them to go after multiple protein targets with just one drug.

Former Merck & Co. executive Bruce Beutel, computational chemist and serial entrepreneur Soumya Ray, and systems biologist and former Biogen leader William Chen joined forces about 2 years ago to found a start-up called Passkey Therapeutics. On Tuesday, they launched the Cambridge, Massachusetts–based firm publicly and announced it had raised $20 million in seed funding led by Breakout Ventures.

Passkey’s play is a class of drug candidates the start-up calls SMThs—pronounced “smiths” and short for “synergistic multifunctional therapeutics.” The drug candidates are designed to target pairs or groups of proteins that cause disease when they work together.

“The industry’s pretty dominated by a single-protein-as-a-target paradigm. You pick one protein that’s associated with a disease, and then you modulate its activity in some way with the drug,” says Beutel, who serves as Passkey’s CEO. “The problem with this is that it’s not going to work that well most of the time. [There’s a] disconnect between this reductionist, simple approach of targeting one protein and the complexity of the biology itself.”

Other researchers have tried to tackle this problem before; bispecific antibodies, for instance, can bind to two target antigens at once. Beutel and his 15-person team plan to build on that work by developing single drugs—some small molecules, some antibodies—that can tackle multiple protein targets together.

To identify those groups of proteins, Passkey has developed a software platform it calls Locksmith. The tool analyzes human genetic data to find combinations of proteins involved in complex diseases, then models potential drug candidates that could modulate them. Some of those drug candidates will certainly be small molecules, Beutel says, because they’re better at hitting targets inside the cell than larger molecules like antibodies are.

Passkey’s multifunctional compounds could potentially be used to treat cancer, autoimmune and neurodegenerative disorders, and metabolic diseases. The company will develop drug candidates in-house for two unnamed disease areas and seek partnerships with pharmaceutical companies to expand its reach. Beutel declines to offer a drug development timeline.

“After all the experience I’ve had in different roles and companies big and small, I immediately felt this was kind of the only thing that mattered now,” Beutel says. “It just has to be solved.”