Scientific Approach

Innovators in Synthetic Lethality

At Cyteir, we employ an integrated target discovery approach that incorporates a critical evaluation of the target biology with internal and external information from a variety of genetic and chemical synthetic lethality screens to fuel our drug discovery and development pipeline.

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 targets based on a critical evaluation of the target 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 as a monotherapy, and assuring tumor selectivity that limits side effects and allows our drugs to be used in combination with other standard anti-cancer therapies
3. Developing potent, highly selective, well-tolerated 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