Reversing the advantage of cancers with Hypoxia and Homologous Recombination Defect (HRD) by using a pan-cancer, composite, lesions-specific biomarker

Hypoxia-activated prodrugs (HAPs) are a great concept in particular in association therapies more efficient on well-oxygenated cells, such as immunotherapies.

CP-506 is a third generation HAP with optimal PK for which we confirmed in more than 20 tumor models that presence of tumor hypoxia is a requisite for prodrug activation. We already had an AI/radiomics-based proprietary IP on a solution to identify hypoxia from standard imaging.

Another important determinant for efficacy was the presence of a defective homologous recombination (HRD), a pathway needed to repair the DNA damage of the alkylating warhead of CP-506.

A genome-wide mutational scar-based pan-cancer Classifier of HOmologous Recombination Deficiency (CHORD, available open source) is able to detect HRD better as compared to assessing mutation of key genes. It is therefore essential to have a validated software solution integrating both biomarkers.

This solution, further developed in this project, will be able to capture intrapatient heterogeneity and make a outcome prediction per patient and per lesion.