Platform
Precision PGx Platform
Optimized over more than four years, our Precision PGx Platform can rapidly screen small molecules against all significant driver mutations in vitro.
Three aspects of the platform are critical to its ability to identify existing compounds that can be developed as genetically targeted therapeutics:
Founded on synthetic lethality
Our Precision PGx Platform is designed to identify synthetic lethality relationships with a focus on driver genes with loss of function mutations. This approach allows Leapfrog to evaluate targeted therapeutic opportunities for the approximately two-thirds of cancers that cannot be addressed with conventional targeted approaches.
Replicates tumor causing biology
Our platform incorporates a deeply optimized set of CRISPR guides and carefully selected cell lines in order to create genetic perturbations that precisely match, and are functionally equivalent, to actual tumor causing mutations. By accurately replicating the biology of cancer, we greatly enhance the translatability of our discoveries.
Identifies effective drugs, not just drug targets
Leapfrog¹, and others², have shown that the biologic effect of a drug is seldom the same as the effect of genetically perturbing the target of the drug. By screening actual drugs, we identify compounds that potently induce a synthetically lethal effect, and do not need to spend years attempting to create a molecule that replicates the effects of genetic perturbation.
Synthetic Lethality Predictions Clinically Validated
The accuracy of the Precision PGx platform has been demonstrated through a retrospective study of the effects of commonly used chemotherapeutics. We screened 20 approved therapies to identify putative synthetic lethality relationships that had not been previously described. We then retrospectively analyzed real world clinical data of patients who had been treated with those therapies and their outcomes. In the vast majority of cases, this analysis confirmed that patients with a driver mutation identified by our platform as synthetically lethal with their particular treatment option had better survival rates than patients without the sensitizing mutation receiving the same treatment.