Roche licenses drug to target cancer DNA damage response

According to the terms of the deal, whose value is undisclosed, Roche will pay KSQ an upfront payment in addition to potential milestone and royalty payments. Roche in turn will gain a global license for the development of KSQ-4279 in 2024.

KSQ-4279 is a first-in-class small molecule drug that blocks a protein target called ubiquitin specific peptidase 1 (USP1). The protein plays a key role in the repair of DNA molecules in cells and is an emerging target for drugs blocking DNA damage response (DDR). Healthy cells are typically resistant to DDR blockers because they have multiple DDR mechanisms to fall back on. In contrast, cancer cells from multiple tumor types that already have mutations in their DDR machinery can be killed by DDR inhibitors.

KSQ-4279 is currently in phase 1 testing in patients with solid tumors. The candidate is being tested both as a monotherapy and in combination with either chemotherapy or with a common type of DDR blocker called a PARP inhibitor.

KSQ uses a platform called CRISPRomics to screen all genes in the human genome in different cancer models to detect which can be used as suitable treatment targets and patient-selective biomarkers. With the help of this platform, based on the famous gene editing tool CRISPR-Cas9, genes can be turned on and off in tumor cell screens efficiently in the lab​ without needing to find small molecule blockers of each gene.

KSQ is also deploying its platform to develop cell therapies for cancer based on immune cells including tumor infiltrating lymphocyte (TIL) cells and natural killer (NK) cells. The company uses gene editing to discover which genes can be inactivated to power up T cell therapies and potentially require a lower dose than current cell therapies.

“We believe KSQ-4279, which was discovered through our proprietary CRISPRomics platform, has incredible potential to help patients with a variety of solid tumors based on the strong preclinical data we have seen to date,” said Qasim Rizvi, CEO of KSQ in a public statement. “We are confident Roche is the right partner to further the development of KSQ-4279 and maximize its benefits for patients.”

“For KSQ, this agreement enables us to fully focus our attention on advancing our own immunotherapy programs and to continue leveraging our successful platform to discover novel targets.”

One of the first DDR blockers to be approved by the U.S. Food and Drug Administration (FDA) was olaparib (Lynparza) in 2014. Since then, the drugs have attracted major interest from Roche and other big pharma companies.

In June 2022, for example, Roche sealed a licensing agreement with the company Repare Therapeutics to access its DDR blocker camonsertib, this time blocking the protein ATR. Earlier this year, the Swiss company Debiopharma got the global development rights​ to a USP1 blocker from Novo Nordisk.