• Study published in American Journal of Transplantation highlights strong sensitivity and specificity, along with a >37% reduction in false positives when using Prospera Heart with DQS
• Adds to the growing body of evidence supporting DQS for dd-cfDNA analysis in solid organ transplant

AUSTIN, Texas / May 07, 2025 / Business Wire / Natera, Inc. (NASDAQ: NTRA), a global leader in cell-free DNA and precision medicine, today announced that the American Journal of Transplantation (AJT) published a new study¹ evaluating the performance of Prospera Heart with DQS to detect allograft rejection.

Prospera with DQS leverages a two-threshold algorithm, combining the traditional donor fraction (dd-cfDNA %, measuring dd-cfDNA as a fraction of total cfDNA) and donor quantity score (DQS, estimating the total quantity of dd-cfDNA in the blood). This method delivers a single result for risk assessment of both antibody mediated rejection (AMR) and acute cellular rejection (ACR).

In the study, 808 Prospera Heart test samples were obtained from 187 heart transplant patients alongside paired endomyocardial biopsies. Prospera with DQS was compared to dd-cfDNA %-alone to assess the detection of biopsy-proven allograft rejection. The study highlights the following performance improvements demonstrated by Prospera with DQS, including:

• Sensitivity increased from 78.2% to ​​86.5%.
• Specificity increased from 76.9% to 83.6%.
• Area under the curve (AUC) increased from 0.865 to 0.881
• A reduction in false positive cases of 37.3%

“This publication provides evidence that combining dd-cfDNA % with DQS improves the accuracy of dd-cfDNA testing for acute rejection over dd-cfDNA %-alone,” said Josef Stehlik, M.D., M.P.H., one of the study investigators and medical director of the Heart Transplant Program and co-chief of the Advanced Heart Failure Program at the University of Utah. “It is encouraging to see that this novel approach significantly reduced false positive results and will help to obviate unnecessary biopsies in clinical care. This is another step in providing enhanced care for heart transplant patients using noninvasive tools to determine risk of rejection.”

This data confirms the growing body of evidence for the utilization of DQS when analyzing dd-cfDNA in solid organ transplant, including a study evaluating DQS in kidney transplant (Halloran et al). Natera has also demonstrated the value of DQS in the supplemental data from its 2022 DEDUCE study² in Prospera Heart, as well as recently announced data from the DEFINE-HT study.

“Ongoing datasets continue to demonstrate the robust performance of Prospera Heart with DQS, indicating its potential to reduce reliance on endomyocardial biopsies – procedures that carry inherent risk and cause patient discomfort,” said Michael Olympios, M.D., Medical Director of Heart Transplant at Natera. “In addition to the DEFINE study we presented at ISHLT and the randomized ACES trial now in progress, our research remains dedicated to refining diagnostic approaches and improving clinical outcomes for heart transplant recipients.”

About Prospera

The Prospera™ test leverages Natera’s core single-nucleotide (SNP)-based massively multiplexed PCR (mmPCR) technology to identify allograft rejection non-invasively and with high precision and accuracy, without the need for prior donor or recipient genotyping. The test works by measuring the fraction of donor-derived cell-free DNA (dd-cfDNA) in the recipient’s blood. It may be used by physicians considering the diagnosis of active rejection, helping to rule in or out this condition when evaluating the need for diagnostic testing or the results of an invasive biopsy. The Prospera test has been clinically and analytically validated for performance regardless of donor relatedness, rejection type, and clinical presentation.

About Natera

Natera™ is a global leader in cell-free DNA and genetic testing, dedicated to oncology, women’s health, and organ health. We aim to make personalized genetic testing and diagnostics part of the standard-of-care to protect health and inform earlier, more targeted interventions that help lead to longer, healthier lives. Natera’s tests are supported by more than 250 peer-reviewed publications that demonstrate excellent performance. Natera operates ISO 13485-certified and CAP-accredited laboratories certified under the Clinical Laboratory Improvement Amendments (CLIA) in Austin, Texas, and San Carlos, California. For more information, visit www.natera.com.

Forward-Looking Statements

All statements other than statements of historical facts contained in this press release are forward-looking statements and are not a representation that Natera’s plans, estimates, or expectations will be achieved. These forward-looking statements represent Natera’s expectations as of the date of this press release, and Natera disclaims any obligation to update the forward-looking statements. These forward-looking statements are subject to known and unknown risks and uncertainties that may cause actual results to differ materially, including with respect to whether the results of clinical or other studies will support the use of our product offerings, the impact of results of such studies, our expectations of the reliability, accuracy and performance of our tests, or of the benefits of our tests and product offerings to patients, providers and payers. Additional risks and uncertainties are discussed in greater detail in “Risk Factors” in Natera’s recent filings on Forms 10-K and 10-Q and in other filings Natera makes with the SEC from time to time. These documents are available at www.natera.com/investors and www.sec.gov.

References

1. Kim PJ, Olympios M, Sideris K, et al. A Two-Threshold Algorithm using Donor-derived Cell-free DNA Fraction and Quantity to Detect Acute Rejection After Heart Transplantation. American Journal of Transplantation. Published online May 2025. doi: 10.1016/j.ajt.2025.04.021
2. Kim, PJ, Olymbios M, Siu A, et al. A novel donor-derived cell-free DNA assay for the detection of acute rejection in heart transplantation. The Journal of Heart and Lung Transplantation. 2022. 41(7):919 - 927.