Complex science is the name of the game in the burgeoning field of omics. But when it comes to chemoproteomics, or chemical proteomics, there is one simple analogy to understand what it means for drug discovery. Each covalent small molecule is a kind of “bait” that’s “designed to attract a specific type of fish,” explained Ping Cao, CEO and co-founder of BridGene Biosciences.
The company’s platform, IMTAC, uses chemoproteomics to analyze the interactions between potential drug compounds and cellular proteins to discover targets previously considered “undruggable.” It accomplishes this by screening covalent small molecules against proteins to find ones they can bind with.
“These fish represent the protein,” he said. “When covalent small molecules are introduced into the live cells, the selectivity will capture different proteins, much like different types of bait attract different types of fish species.”
So far, the bait is catching fish.
BridGene’s pipeline consists of four candidates in oncology, including a novel TEAD inhibitor to treat advanced solid tumors with hippo pathway dysregulation. The company announced in June that the first patient has been dosed in its phase 1 clinical trial.
Now, Takeda is tapping BridGene’s platform in a new deal to discover novel small molecule candidates for traditionally hard-to-drug targets in immunology and neurology. Under the agreement, worth a potential $770 million, Takeda will pay BridGene $46 million in combined upfront and potential preclinical milestone payments, and more if the company hits certain milestones.
The partnership marks the third time the two companies have worked together, including a pilot program in 2020 and a $500 million drug discovery matchup in 2021.
“We achieved several different preclinical milestones for that deal,” said Irene Yuan, BridGene’s co-founder and executive vice president.
Among the previous deal’s successes were identifying a drug candidate for the “root causes of debilitating neurological disorders” and achieving a second clinical milestone a few months later, according to two 2023 BridGene press releases.
The lowdown on chemoproteomics
Proteomics is one of many different “omics” sciences that study entire sets of biological molecules. Genomics, which involves the genome, is the most well-known, but the field has broadened to include transcriptomics, metabolomics, lipidomics and epigenomics, among others.
Given its potential for drug discovery, pharma companies are increasingly investing in the omics-based approach. Late last year, GSK forked over $35 million in upfront cash to leverage Muna Therapeutics’s spatial multi-omics platform to discover Alzheimer’s targets, and could pay up to $147.6 million per target.
Proteomics studies proteins, and chemical proteomics identifies protein binding targets of small molecules in live cells. That’s where BridGene’s IMTAC platform comes in. IMTAC is differentiated from other platforms by its ability to screen the proteome, which is the entire set of proteins, rather than focusing on individual targets.
“The whole proteome contains probably more than 20,000 different proteins. And so far in drug discovery, the whole industry has developed or discovered drug candidates for maybe less than 10% of those proteins,” Yuan said.
In addition, many of these proteins are considered tough to treat.
“How to make those proteins druggable is one of the biggest challenges for the industry,” Yuan said. “Now we have this chemical proteomics tool which enables us to screen the whole proteome of live cells, enabling us to discover small molecule drugs for a lot of different, hard-to-drug targets in a short period of time and with very high throughput."
So far, she said they’ve identified small molecule ligands for more than 4,000 different proteins “and this number is still growing.”
When BridGene identifies a protein with therapeutic potential, it can move fast.
“We have already identified small molecule ligands for it, which enables us to kick off the drug discovery and the drug development process very quickly,” Yuan said.
Yuan said BridGene plans to continue its own internal drug development, as well as pursue collaborations with large pharmaceutical companies like Takeda. It will also choose which proteins to focus on for its own internal drug development or for out-licensing. She added that the company is currently closing its new round of fundraising and plans to seek a crossover round and start the IPO process by the end of next year.
According to Yuan, BridGene could play an important role in the industry’s future focus on hard-to-drug targets.
“A lot of the most easy-to-drug targets have been drugged. Nowadays, people are facing a strategy of how to address those hard-to-drug targets,” she said. “I’d like to emphasize the importance of covalent drugs in this hard-to-drug target area.”
