GSK sets out to crack 'undruggable' targets, with a little help from Warp Drive Bio

Each company will independently develop and commercialize products against their respective targets.

Despite huge advances in molecular medicine, vast swathes of disease-associated proteins remain undruggable—in other words, they lack an obvious active site to which a small-molecule drug can bind or are found within cells out of reach of biologics.

Not for much longer, if GlaxoSmithKline and Warp Drive Bio have their way. The two companies have just agreed on a high-tech alliance that will try to unlock the 80% or so of human proteins considered undruggable to conventional drug discovery techniques and open up new opportunities to develop medicines for intractable diseases such as cancer.

GSK is bringing to the program its DNA-encoded library technology, which is based on the synthesis and screening of a diverse collection of around a trillion small molecules—tagged with specific DNA sequences that serve as unique molecular barcodes—which can be screened against drug targets.

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Warp Drive Bio meanwhile will contribute its SMART platform, which creates small-molecule drugs that bind to an intracellular receptor—or presenter protein—to create a complex that is effectively a biologic drug operating within the cell.

The result of putting the two platforms together is "an unprecedented library of up to 200 million diverse SMART compounds for the discovery of lead chemical matter against a set of currently inaccessible targets," according to Alan Rigby, Ph.D., Warp Drive Bio's chief scientific officer.

The library will be screened against "a set of undruggable targets related to diseases of high unmet medical need," according to the two partners, which do not go into further details. To date Warp Drive Bio has concentrated on pathways involving RAS, SHP2 and Cbl-b, which are considered interesting targets for solid tumor and blood cancer therapies.

Each company "will independently develop and commercialize products against its respective targets," said the partners. Financial terms have not been disclosed, but the deal adds to Warp Drive Bio's list of Big Pharma partnerships, which also include a $750 million, five-year alliance with Sanofi focused on the RAS oncogenic protein and a Gram-negative antibiotic program.

"Our SMART platform builds on mechanisms adopted and evolved by nature to modulate intractable targets," said Laurence Reid, Ph.D., Warp Drive Bio's president and CEO. "The partnership with GSK allows us to tap into unique chemical diversity inspired by nature in search of new transformative medicines to treat human disease."

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