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

Introduction

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

Overview of CP-506

CP-506 is a third generation HAP with optimal pharmacokinetics (PK). We confirmed in more than 20 tumor models that the presence of tumor hypoxia is a requisite for prodrug activation.

AI and Imaging Solutions

We already had an AI/radiomics-based proprietary intellectual property (IP) on a solution to identify hypoxia from standard imaging.

Importance of Homologous Recombination Deficiency

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

CHORD Classifier

A genome-wide mutational scar-based pan-cancer Classifier of Homologous Recombination Deficiency (CHORD, available open source) is able to detect HRD better compared to assessing mutations of key genes.

Integration of Biomarkers

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 an outcome prediction per patient and per lesion.