Scorpion Therapeutics, AstraZeneca Ink Deal Focused on “Undruggable” Cancer Targets.

Precision oncology newcomer, Scorpion Therapeutics has announced it will collaborate with big pharma company AstraZeneca, in a deal that will see the two companies work together to develop cancer therapies against previously “undruggable” targets. The collaboration will focus on hard-to-target proteins called transcription factors (TFs) that control gene expression and can regulate cell growth and survival.

Despite being promising drug targets for cancer treatments as known drivers of cancer, TFs, outside of nuclear receptors, have proven hard to address with traditional small-molecule therapeutic development approaches. The fundamental difficulty is that TFs are predominantly intrinsically disordered and lack classical well-formed small-molecule binding pockets. In fact, while more than 300 TFs have been associated with disease phenotypes, only a very small number have been successfully targeted with small molecules.

Under the terms of the agreement, Scorpion will lead discovery and certain preclinical activities, while AstraZeneca has the exclusive option to license worldwide rights for up to three drug candidates. AstraZeneca would be responsible for development and commercialization activities worldwide following opt-in, while Scorpion would retain the option to co-develop and co-promote up to two of these programs in the U.S. under certain conditions, including if AstraZeneca exercises three license options.

The deal provides $75 million upfront for Scorpion and has the potential to generate for the company as much as $1.5 billion in option fees and milestone payments, as well as tiered royalties on net sales ranging from mid-single digit to low-double digits.

“Unlocking potentially transformative biology is pivotal for delivering the next wave of cancer treatments,” said Susan Galbraith, EVP, oncology R&D at AstraZeneca in a press release. “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.”

Scorpion is pursuing what it terms “Precision Oncology 2.0” which combines advanced technologies in cancer biology, medicinal chemistry, and data science into a single platform to create selective small molecule compounds against a broad spectrum of targets. The company leverages technologies such as genome-wide CRISPR, RNA or resistance mutation screening; integration of broad data sets including TCGA, the Cancer Cell Line Encyclopedia, and DepMap; leverages cloud-based super-computing with its proprietary algorithms to create more focused “drug-like” library designs.

“We are pleased to enter into this collaboration with AstraZeneca, whose expertise in drug development and commercialization complements our discovery platform, which leverages cutting-edge advances in cancer biology and medicinal chemistry, including chemical proteomics, structure-based drug design and machine learning,” noted Axel Hoos, CEO of Scorpion in a prepared statement. “We expect this collaboration will accelerate Scorpion’s efforts to deliver the promise of Precision Oncology 2.0: optimized, transformational therapies for more patients living with cancer.”

Scorpion was founded in October 2020 and launched with a $180 million Series A financing led by led by Atlas Venture, Omega Funds, and Vida Ventures, with participation from Abingworth and Partners HealthCare Innovation. The company’s founders bring deep and relevant experience to the company having served in senior positions with companies such as IFM Therapeutics, Novartis, and Amgen, as well as from prominent academic medical centers and research institutions including Massachusetts General Hospital, Harvard Medical School, and the Broad Institute.

“Their investments in data sciences and next-generation chemistry power a discovery engine that is purpose-built to find the best drugs for proven targets, as well as exploit novel ones. We look forward to supporting the Scorpion team in their mission to change the landscape of cancer treatment,” said Arjun Goyal, co-founder and managing director at Vida Ventures at the time of its Series A financing.