Takeda taps BridGene to pursue hard-to-drug neurodegenerative disease targets

Takeda has teamed up with BridGene Biosciences to discover small molecules against targets once thought to be undruggable. The five-program agreement, which is potentially worth more than $500 million, wraps up a busy month for deal-making at Takeda.

BridGene’s pursuit of undruggable targets is enabled by two core technologies. The California-based biotech uses covalent drugs to bind to targets and chemoproteomics to analyze interactions between small molecules and proteins in living cells. While most drugs form reversible bonds with targets, the history of covalent small molecules dates back to aspirin. In recent years, researchers have begun to more systematically search for covalent drugs to tackle hard targets, perhaps most notably KRAS.

Takeda is stepping up its activities in the space by making a one-time upfront payment of undisclosed size to access BridGene’s IMTAC platform. Across five drug discovery programs, the partners will work to identify targets and small-molecule drug candidates for Takeda to take into clinical development.  

The programs will give BridGene a chance to validate its technology. By combining chemoproteomics and covalent small molecules, BridGene will try to identify the targets responsible for the onset and progression of disease and show which targets a drug candidate interacts with in live cells. In doing so, BridGene predicts it can quickly advance from hit to lead.  

BridGene has worked quietly on the approach in recent years, with public information on the progress of the biotech limited to a pair of press releases from 2018 and disclosures of government grants to support development of the chemoproteomics platform and an irreversible covalent inhibitor of FLT3 for treating acute myeloid leukemia.

The early focus on tyrosine kinase FLT3 is in keeping with covalent R&D successes stories and the background of BridGene’s scientific founder Chao Zhang, who did his postdoc under Kevan Shokat. Zhang now chairs BridGene’s scientific advisory board. Ping Cao, Glenn Begley and Michael Bishop, formerly of companies including Amgen and GlaxoSmithKline, are CEO, head of biology and head of chemistry, respectively. 

BridGene landed the Takeda deal, which features preclinical, clinical and commercial milestone payments that could increase its value to north of $500 million, after completing a pilot project. The initial research program is focused on “targets that contribute to a disease phenotype that is believed to underlie neurodegenerative disease and is modifiable by small molecules in a phenotypic screen,” BridGene said. Takeda can add up to four more programs to the collaboration.

The neurological focus of the initial research program is in keeping with Takeda’s recent deals. In March alone, Takeda has agreed to pay up to $120 million in upfront fees and preclinical research milestones to work with Anima Biotech on molecules against hard-to-drug proteins, starting with a Huntington’s disease program, and put up $196 million to regain the rights to an epilepsy drug from Ovid. Along the way, Takeda struck a $525 million buyout of oncology biotech Maverick Therapeutics.