AstraZeneca joins KRAS push in cancer with Chinese deal

AstraZeneca has added to its oncology pipeline by licensing a small-molecule KRAS inhibitor from Chinese biotech Usynova for $24 million upfront.

The compound – called UA022 – targets the KRASG12D mutation and is currently still in preclinical development. AZ has taken an exclusive worldwide license to the drug in a deal that also includes up to $395 million in development and commercial milestone payments as well as royalties on future sales.

If it makes it through to market, UA022 would follow in the footsteps of pioneering KRAS inhibitors Amgen’s Lumakras (sotorasib) and Mirati’s Krazati (adagrasib), which have been approved as second-line therapies for KRAS-mutated non-small cell lung cancer (NSCLC) but target KRAS G12C, a different mutation.

KRAS G12C is the most common form of KRAS mutation in lung cancer, while G12D is found more commonly in other diseases like pancreatic and colorectal cancers.

Dr Hu Tao, co-founder and chief executive of Usynova, which is also known as Yousen Jianheng Biopharmaceutical, said in a statement that KRAS G12D is the most common KRAS mutation in cancer, accounting for around 26% of all KRAS mutations overall, but there are currently no approved drugs specifically targeting it.

According to Usynova, UA022 has shown potent anticancer activity in lab testing, with good oral bioavailability and a “favourable” safety profile.

With the licensing deal, AZ joins a select group of companies going after the target that includes Mirati – soon to become part of Bristol-Myers Squibb if a $5.8 billion takeover deal goes through – as well as Revolution Medicines, Quanta Therapeutics and Roche/Chugai.

Mirati’s MRTX1133 is in phase 1/1b testing, with results as a monotherapy due in the first half of next year and studies also underway of the drug in combination with cancer immunotherapies. Revolution’s RMC-9805 recently started a phase 1/1b study with results expected in 2025.

Roche/Chugai’s pan-RAS inhibitor LUNA18 has already completed a dose-ranging study while Quanta’s multi-KRAS inhibitor QTX3034 is in preclinical development.

Stephen Fawell, AZ’s head of oncology development, described the licensing deal as an “exciting opportunity” that builds on AZ’s “heritage of targeting tumour drivers and mutations.” He added that the deal “could accelerate the development of potential new treatments for patients whose tumours carry the KRAS G12D mutation, an area of unmet medical need.”