Clinical Applicability of Circulating Nucleic Acids

Clinical Applicability of Circulating Nucleic Acids

Abstract
This talk will provide an overview of the technical approach and resulting products that have been developed by Natera over the past 12 years. By continuously building and expanding on its molecular biology and algorithmic technology toolkit, Natera has launched several products utilizing molecular techniques to measure and derive clinically meaningful results from cell-free DNA (cfDNA).
Panorama, Natera’s NIPT test for trisomies 13.18 and 21 as well as several key microdeletions was the initial product extensively studied. The primary objective of the SMART study (“SNP-based Microdeletions and Aneuploidy RegisTry) was to measure the performance of SNP-based NIPT in a prospective study for the common trisomies, monosomy X, and microdeletions. Highlights of the study analysis demonstrated high levels of sensitivity and specificity for both the initial algorithm and the exploratory AI analysis.The SMART study remains by far the largest study (20887 participants from 21 centers) utilizing genetic ‘truth’ for nearly 90% of the participants.
Observations within collaborative studies and routine clinical testing on challenging samples led to the analysis of additional findings in expectant mothers that show further applications for cfDNA, such as detection of cfDNA from transplanted graft organs. This led ultimately to the validation of Prospera for monitoring organ health in the post transplant period. To date clinical cut-offs for kidney, heart and lung transplant surveillance have been clinically validated, with additional studies underway in lung and multi-organ transplant.
Additionally it is possible to measure copy number variations in the expectant mother and detect maternal malignancies during cfDNA based testing methodologies. Such cases are studied and provided clinical care in detail in the example of the IDENTIFY cohort, led by the NIH, and Natera offering a referral program to this study.
Another application of cfDNA led to the development and launch of the Signatera™ test, a personalized, tumor-specific, diagnostic test for the detection of molecular residual disease (MRD). Signatera™ tracks patient-specific single nucleotide variants over time. Signatera™ has been shown to identify MRD with high sensitivity and specificity in patients who have previously been diagnosed with cancer, predicting relapse months ahead of radiological imaging.
In summary, Natera has applied cfDNA technologies in a variety of disease settings and applications to high medical value challenges for better management of disease and improving patient outcomes.