After pilot project, Takeda inks $500M pact to tap into a Kevan Shokat protégé's covalent small molecule fishing platform
As new technologies open up new avenues toward targets widely considered undruggable by small molecules, Takeda is taking a chance on a low-profile drug discovery player with promises of up to $500 million in biobucks.
Over the next two years, Sunnyvale, CA-based BridGene will deploy its chemical proteomics-based platform for five programs against targets of interest, starting with one implicated in neurodegenerative diseases.
It all started, according to BridGene CEO Ping Cao, with an in-person meeting at JP Morgan last January.
“If you talk to a chemist or scientist in a large firm, they always say we are target hungry,” he said.
Cao, who spent enough years at Amgen’s San Francisco site to be approaching lifer status, knew the issue well. With the low-hanging fruit already picked, remaining disease-causing proteins often have pockets that are either too shallow (think KRAS) or transient, presenting themselves only in live cells (think transcription factor).
Takeda was no different. The pharma giant has a large phenotypic screening facility in Japan where scientists identify phenotypic changes caused by molecules in their library, but there’s a major hurdle in figuring out what exactly caused the change. Once Cao presented their technology, it took little time to kickstart a pilot project in which Takeda handed over some of their clinical candidates for BridGene to profile.
“We use covalent small molecules as a bait,” he said. “So we fish inside live cells. So live cells are like an ocean; each protein is just like a fish there. Different small molecules, they will fish out different targets or different proteins.”
The core technical expertise came from scientific founder Chao Zhang’s lab at the University of Southern California. Having trained with Kevan Shokat, the inventor of one of the earliest KRAS G12C inhibitors, Zhang came up with his own method of mining covalent kinase inhibitors, collaborating with Principia co-founder Jack Taunton along the way. That company, which boasts of BTK inhibitors, sold to Sanofi for $3.7 billion. Shokat, meanwhile, is on the scientific advisory board.
From March to September, BridGene’s team of 10 put several Takeda cancer drugs through its platform and came up with a report detailing how many proteins bound to those small molecules — some previously unknown to the pharma partner.
“Takeda was really happy with the results because this report helped them to — they can decide if they want to pursue other indications that cover other targets they didn’t know before,” he said. “It also gave them (a) broad full view of the potential toxicity concerns down the road.”
It paved the way for the current collaboration, Cao said, which takes the same technology in a slightly different direction. The biotech will be tasked with identifying new targets that are responsible for a specific disease phenotype that Takeda pinpoints as underlying a neurodegenerative condition, or other ailments in the future phases of the pact.
The undisclosed upfront cash, added to a pre-A round they’ve raised, would help fund BridGene’s internal pipeline of oncology programs, Cao added.
For Takeda, the alliance marks the latest in a discovery deal spree covering everything from RNA-binding small molecules and ribosome drug testing machines to CRISPR-screened cell therapies and LNP gene delivery.