Trifecta Study Establishes New Validation Standard for dd-cfDNA in Kidney Transplant Rejection With Largest Prospective, Multisite, Fully Biopsy-Matched Study

Statistically significant performance improvement from using both dd-cfDNA fraction and dd-cfDNA quantity vs. dd-cfDNA alone

AUSTIN, Texas, June 29, 2022/PRNewswire/ -- Natera, Inc. (NASDAQ: NTRA), a global leader in cell-free DNA (cfDNA) testing, today announced the publication of a manuscript in a leading journal in the organ transplant space, Transplantation, validating the performance of a novel two-threshold algorithm for its Prospera™ test for the assessment of transplant rejection. Prospera incorporates the donor fraction and the estimated amount of donor-derived cfDNA (dd-cfDNA) when assessing active rejection. In the study, Natera's new method demonstrated significantly improved performance compared to rejection assessment using donor fraction-alone.

The "Trifecta" study, led by principal investigator Phil Halloran, M.D., Ph.D., director of the Alberta Transplant Applied Genomics Centre, is currently enrolling at 25 sites globally. The first 367 samples from adult kidney transplant recipients meeting enrollment criteria were analyzed and included in the manuscript. These samples represent the largest prospective, fully biopsy-matched cohort with dd-cfDNA analysis for kidney transplant recipients conducted to date. Assessment of active rejection by the Prospera test was evaluated against RNA-based molecular pathology (Molecular Microscope® Diagnostic System, "MMDX") and histological (Banff Classification of Allograft Pathology, 2019) assessment of the biopsy. The cohort in the Trifecta study features a total of 125 samples with biopsy-proven active rejections by MMDX and 142 samples with biopsy-proven rejection by BANFF criteria used to benchmark dd-cfDNA calls, exceeding both the 27¹ samples and the 113² samples from biopsy-proven active rejections in previous dd-cfDNA testing studies.

The Prospera assay exceled at discriminating between active rejection and non-rejection, with AUCs of 0.88 assessed with MMDX, 0.82 assessed using the BANFF criteria, and an AUC of 0.91 compared to quiescence. The excellent performance further highlighted the value of the Prospera two-threshold algorithm, as the combination of dd-cfDNA fraction and estimated amount of dd-cfDNA outperformed either variable alone. The two-threshold algorithm detected six additional cases of rejection compared to using donor fraction-alone.

"This study shows that dd-cfDNA test performance, using the two-threshold approach, is substantially improved, and is highly correlated to other molecular methods such as MMDx," said Dr. Halloran. "This is a key piece of evidence supporting the routine utilization of molecular methods to complement traditional biopsies for diagnosing rejection."

"Our legacy of expertise in cfDNA analysis has enabled us to maximize the knowledge we derive from our tests, providing transplant recipients and their physicians with clinically actionable information from a single test," said Sangeeta Bhorade, M.D., chief medical officer for organ health at Natera. "The excellent AUC of the Prospera test in this study establishes the importance of leveraging the combination of dd-cfDNA fraction and quantification vs donor-fraction alone."

About the Prospera test

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. It has been developed and its performance characteristics determined by Natera, the CLIA-certified laboratory performing the test. The test has not been cleared or approved by the US Food and Drug Administration (FDA). CAP accredited, ISO 13485 certified, and CLIA certified.

About Natera

Natera™ is a global leader in cell-free DNA 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 validated by more than 100 peer-reviewed publications that demonstrate high accuracy. 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, visitwww.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 our efforts to develop and commercialize new product offerings, 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.

Contacts
Investor Relations: Mike Brophy, CFO, Natera, Inc., 510-826-2350
Media: Kate Stabrawa, Communications, Natera, Inc., [email protected]

References

1. Bloom RD, Bromberg JS, Poggio ED, et al. Cell-Free DNA and Active Rejection in Kidney Allografts. J Am Soc Nephrol. 2017;28(7):2221-2232.
2. Bu L, Gupta G, Pai A, et al. Clinical outcomes from the Assessing Donor-derived cell-free DNA Monitoring Insights of kidney Allografts with Longitudinal surveillance (ADMIRAL) study. Kidney Int. 2022;101(4):793-803.

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