AZ, Scorpion strike deal on elusive transcription factor targets in cancer

AstraZeneca has expanded its efforts to develop new therapies targeting transcription factors – proteins that regulate processes in the cell that have become a hot topic for drug discovery in cancer and other diseases.

The UK-headquartered pharma is buying into a drug discovery platform developed by Boston, US biotech Scorpion Therapeutics, paying $75 million upfront to get the ball rolling on the partnership, with undisclosed option fees and milestone payments also on offer.

Scorpion has assembled a drug-hunting engine to develop small-molecule drugs that can target proteins and other biological targets, seeking out binding areas in molecules that have previously been considered “undruggable”.

Transcription factors – which control gene expression and can regulate important cellular processes, including cell growth and survival – have traditionally been held to fall into the undruggable category, with fewer than 1% of them successfully targeted for therapeutics.

New R&D techniques that have unlocked the 3D structure of complex molecules have, however, started to render the term obsolete. Recall that KRAS was considered an undruggable target for decades before Amgen found a suitable binding region on the protein and bought an inhibitor to market for lung cancer.

AZ’s deal with Scorpion is also focused on oncology, with the biotech leading discovery and certain preclinical activities, while AZ has an exclusive option to licence worldwide rights for up to three drug candidates.

It’s not the big pharma’s first foray into the transcription factor area. In 2020, it joined forces with UK start-up MiNA Therapeutics to develop small activating RNAs (saRNAs) that can indirectly affect transcription factors and dial the production of disease-associated proteins up or down.

That project is focusing not on cancer but metabolic diseases, although MiNA’s in-house efforts have already yielded one clinical candidate that activates the CEBPA gene, which codes for a transcription factor that drives drug resistance in cancer cells.

There’s a growing list of biotechs working on transcription factor-based therapeutics, including Sangamo, Flare Therapeutics, Kronos Bio, Arpeggio Bio, Foghorn Therapeutics, Cellestia Biotech and others.

“Unlocking potentially transformative biology is pivotal for delivering the next wave of cancer treatments,” said AZ’ head of oncology R&D Susan Galbraith.

“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,” she added.

Image by Patrizia08 from Pixabay 

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