MRD-EDGE: Ultra-Sensitive Detection of Circulating Tumor DNA for Cancer Screening and Diagnosis

Background & Unmet Need

• Liquid biopsy is an emerging noninvasive method for cancer diagnosis and monitoring which involves sequencing blood plasma cell-free DNA (cfDNA) to identify circulating tumor DNA (ctDNA)
• ctDNA detection is of particular interest for evaluating minimal residual disease (MRD), which indicates the lingering presence of cancerous cells after an initial cancer treatment
• Current ctDNA detection methods have inadequate sensitivity in low volume cancer due to the sparsity of ctDNA in blood and usually require a matched tumor sample, which may not be feasible in many clinical settings
• Unmet Need: A sensitive noninvasive liquid biopsy platform to accurately detect residual tumor in blood samples at low tumor burden in the tumor-informed or tumor-naïve context

Technology Overview

• The Technology: MRD-EDGE is an ultra-sensitive machine learning-guided ctDNA analysis platform for MRD detection in low tumor fraction cancers
• MRD-EDGE incorporates simultaneous profiling of single nucleotide variants (SNV) and copy number variants (CNV) to enhance ctDNA detection
• The deep learning SNV classifier integrates properties of somatic mutations to distinguish ctDNA from sequencing error, enabling ctDNA detection even in the parts per million range and below
• The CNV module couples read-depth denoising with fragmentomics and an allelic imbalance classifier to detect ctDNA even at low aneuploidy levels
• PoC Data: MRD-EDGE enabled tracking tumor burden changes in response to immunotherapy in non-small cell lung cancer (NSCLC), ctDNA shedding in precancerous colorectal adenomas, and de novo mutation calling in melanoma, yielding clinically informative tumor fraction monitoring

Technology Applications

• Ultrasensitive MRD detection following surgical resection of cancer
• Noninvasive liquid biopsy for cancer screening
• Real-time serial monitoring of therapy response to inform therapeutic optimization
• Patient monitoring during remission for early detection of relapse
• Applicability in a wide range of solid tumors

Technology Advantages

• Ultra-sensitive SNV and CNV detection due to advanced error suppression and radical amplification of ctDNA signal
• ctDNA detection in tumor-informed or tumor-naïve context (without matched tumor tissue)
• Simple Whole Genome Sequencing (WGS) workflow does not require custom panel creation or molecular barcodes and can work with limited input material