AstraZeneca to Discover Precision Medicines for Undruggable Targets

AstraZeneca recently collaborated with Scorpion Therapeutics to discover, develop, and commercialize precision medicines against previously undruggable targets.

The companies will focus on a class of proteins called transcription factors. Transcription factors control gene expression and regulate important cellular processes, including cell growth and survival.

Many transcription factors have been used as targets for new cancer treatments and as drivers of disease but have previously been considered undruggable using drug discovery approaches.

“Unlocking potentially transformative biology is pivotal for delivering the next wave of cancer treatments,” Susan Galbraith, executive vice president of oncology research and development.

“Scorpion’s innovative platform is a strong strategic fit as we explore a range of new modalities across our broad drug discovery toolbox with promise to disrupt the activity of these highly-validated cancer targets,” Galbraith continued.

The collaboration will combine Scorpion’s fully integrated discovery platform with AstraZeneca’s leadership in developing and commercializing precision medicines for cancer treatment.

Under the terms of the collaboration, Scorpion will receive an upfront cash payment of $75 million and will lead discovery and certain preclinical activities.

Additionally, the company will retain the option to co-develop and co-promote up to two of these programs in the US under certain conditions.

On the other hand, AstraZeneca will be responsible for the development and commercialization activities worldwide and has the exclusive option to license global rights for up to three drug candidates.

About 85 percent of proteins, including those associated with Alzheimer’s disease and Parkinson’s disease, are beyond the reach of current drugs. 

But in 2021, researchers at Harvard University designed a highly selectiveO-GlcNAc pencil and eraser that add or remove the sugar from a protein with no off-target effects. Researchers can engineer the sugars into new treatments for undruggable diseases using the tool.

Christina Woo, associate professor of chemistry and chemical biology at Harvard University, stated that the selectiveO-GlcNAc is “catalytically dead.”

Therefore, the enzymes won’t make unwanted changes along the way to their target protein and can both add and remove sugars, unlike previous tools, which cause permanent changes.

Once the enzymes are connected to a specific protein function, researchers can use those tools to zoom in and locate where those sugars are latching onto and modifying the protein.