Posted on Oct 27, 2020, 7 p.m.
KSQ Therapeutics is hoping to provide hope for ovarian and breast cancer patients that have developed a resistance to drugs and those who don’t respond at all by developing a drug that may be able to boost the effectiveness of PARP inhibitors such as Lynparza when used in combination with it, and the company has released promising animal data showing promise.
The company’s drug, KSQ-4279, inhibits ubiquitin-specific peptidase I enzymes that have been shown to promote the survival of cancer cells by facilitating DNA repair. The drug is reported to have inhibited tumor growth on its own and when combined with Lynparza in mouse models of ovarian and triple-negative breast cancers according to a presentation at the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics.
The drug was discovered using a CRISPRomics technology platform that allows the identification of therapeutic targets by applying CRISPR-Cas9 gene editing to the entire genome, and the company suggests to have used this platform to study 20,000 human genes in 600 cancer models.
PARP inhibitors are reported to work by interrupting DNA repair, but the company suggests that their drug “inhibits different yet complementary DNA repair pathways,” said the company’s chief scientific officer, Frank Stegmeier, Ph.D. In multiple models of both cancers, the combination was more effective than either drug on their own, and the combination prompted a complete response in some of the breast cancer models.
In 2019 researchers from Yale University discovered that AstraZeneca’s experimental drug candidate VEGF inhibitor cediranib also prevents DNA repair, and that team suggested that cediranib might make tumors more responsive to PARP inhibitors. Recently the FDA approved the combination of Lynparza with Roche’s EGF inhibitor Avastin to treat ovarian cancer with/without BRCA mutations.
KSQ has grown quickly over the past few years with KSQ-4279 now being its lead program, and the new data in ovarian and breast cancers is providing the company with the opportunity to advance their drug candidate into clinical trials “as a novel agent in a new class of targeted oncology treatment.”
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