Roche finds USP in cancer, inking deal with KSQ to expand stable of synthetic lethal candidates

Roche is pushing deeper into synthetic lethality. One year after paying $125 million to join the ATR race, the Swiss drug developer has secured an exclusive global license to KSQ Therapeutics’ early-phase USP1 inhibitor.

USP1 is one of a clutch of emerging targets for synthetic lethality, an approach to killing cancer cells that PARP inhibitors such as AstraZeneca and Merck & Co.’s Lynparza have helped put on the map over the past decade. While PARP inhibitors have validated the concept, they are unable to trigger responses in all patients and are vulnerable to resistance even when they are initially effective.

KSQ identified USP1, a deubiquitinating enzyme that regulates DNA damage response (DDR), as a target for a next-generation candidate, leading to the development of the small molecule KSQ-4279. Roche has identified the candidate as a good fit for its pipeline. 

“DDR is a promising and emerging area of research in oncology,” James Sabry, M.D., Ph.D., global head of pharma partnering at Roche, said in a statement. “We are excited to collaborate with KSQ on their novel inhibitor of USP1 as a potential new treatment option for patients with significant unmet medical needs across a range of cancers.”

Roche has put together a financial package featuring an upfront payment, milestones and royalties for global rights but is yet to disclose how much it is paying. KSQ is currently studying KSQ-4279 in a phase 1 trial. Roche will take full responsibility for further development starting next year.

KSQ is testing the molecule as a monotherapy and in combination with a PARP inhibitor. Roche’s pipeline and portfolio lack an inhibitor of PARP, a space that is fought over by AstraZeneca-Merck, GSK and Pfizer. The Swiss drugmaker has a candidate against another synthetic lethal target, ATR, from the deal it inked with Repare Therapeutics last year.

Licensing a USP1 inhibitor snags Roche a leading position in another cancer race, albeit one that is yet to attract as many Big Pharma companies as ATR. KSQ-4279 is making the early running in a space targeted by companies including Insilico Medicine, Tango Therapeutics and Simcere Pharmaceutical.