At Cyteir, we employ an integrated DNA Damage Response (DDR) target discovery approach that incorporates a deep scientific understanding of DDR biology with proprietary and public information from a variety of genetic and chemical synthetic lethality screens to fuel our drug discovery and development pipeline.
DDR pathway targets are prioritized based on both their role in cancer as well as an identifiable patient population that we predict would benefit from the targeted therapy. To identify patient populations more likely to respond, we leverage insights gained from both classic loss-of-function (LOF) as well as novel gain-of function (GOF) synthetic lethality screens to develop predictive biomarker hypotheses and then test them preclinically.
Our approach includes:
(1) Systematically prioritizing DDR targets based on our deep understanding of DDR biology, coupled with the mining of mutational information collected on diseased tissues and the analysis of results from both internal and external CRISPR-based genetic and chemical synthetic lethality screens
(2) Elucidating synthetic lethality dependencies of our drug targets and using that information to molecularly define patient populations most likely to benefit from our therapies
(3) Developing potent, highly selective small molecule therapies against these targets and evaluating them in biomarker-positive in vitro and in vivo model systems
(4) Expeditiously progressing top candidates through preclinical studies and into focused clinical trials in defined patient populations using a biomarker-guided approach