Natera, Inc.

AUSTIN, Texas--(BUSINESS WIRE)--Natera, Inc. (NASDAQ: NTRA), a global leader in cell-free DNA and genetic testing, announced the results of its DEFINE-HT clinical trial in heart transplantation, which were shared today, April 29, 2025, in an oral presentation at the International Society for Heart and Lung Transplantation 45th Annual Meeting in Boston, MA. DEFINE-HT is the first prospective, multicenter study in heart transplant recipients designed to assess whether elevated levels of donor-derived cell-free DNA (dd-cfDNA), as measured by Prospera Heart with DQS, are associated with adverse clinical outcomes. Following heart transplant, Prospera testing was performed concurrently with rejection surveillance monitoring, including endomyocardial biopsies (EMB), for up to one year. Findings from the study, which included more than 1,100 dd-cfDNA samples, demonstrated that dd-cfDNA significantly correlated with adverse outcomes, a composite endpoint defined as the total number of treated rejections, graft dysfunctions, re-transplantations, and deaths at one year after heart transplant. Key findings include: Patients with at least one elevated dd-cfDNA measurement were significantly more at risk for experiencing an adverse event (HR: 2.56, p=0.0299). Elevated dd-cfDNA predicted graft dysfunction 3x more than biopsy. Prospera with DQS demonstrated a stronger correlation with clinical outcomes compared to donor fraction alone. “The results of DEFINE-HT show that dd-cfDNA can predict clinical outcomes after heart transplantation, which can allow for improved and personalized patient management based on individual risk,” said Palak Shah, M.D., M.S., national principal investigator for DEFINE-HT, director of the Inova Cardiovascular Genomics Center, and medical director of mechanical circulatory support at Inova Fairfax Medical Campus. “Through vigorous research, we continue to drive innovative advancements in heart transplantation, finding less invasive approaches that lead to better patient outcomes.” “In combination with a better understanding of the association of dd-cfDNA and clinical outcomes, DEFINE-HT underscores the utility of Prospera as a tool to help identify patients who may be at risk for adverse outcomes,” said Michael Olympios, M.D., medical director, heart transplant at Natera. “Importantly, the insights gained from this study suggest that Prospera has the potential to obviate invasive surveillance EMB, which will be investigated in an ongoing multi-center, randomized, comparative effectiveness study comparing dd-cfDNA and EMB surveillance (ACES-EMB).” 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.

AUSTIN, Texas--( BUSINESS WIRE )-- Natera, Inc. (NASDAQ: NTRA), a global leader in cell-free DNA and genetic testing, today commented on recent updates by the NCCN on circulating tumor DNA (ctDNA) molecular residual disease (MRD) testing in the Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for colon cancer, rectal cancer, and merkel cell carcinoma (MCC). In its updated guidelines for colon cancer 1 and for rectal cancer 2 , NCCN now includes ctDNA as a high risk factor for recurrence in the adjuvant setting, recognizing its prognostic value. This represents a significant step forward as it’s the first time the committee has formally recognized ctDNA as being prognostic. The guidelines remain cautious about ctDNA for surveillance, as expected. The NCCN finalized these updates before data from the phase III CALGB (Alliance) / SWOG 80702 study were presented at ASCO GI in January, supporting the predictive nature of Signatera in the adjuvant setting. For MCC, the updated NCCN guidelines state that “ ctDNA can assess disease burden in both virus-positive and virus-negative MCC and typically becomes positive prior to or at the time of a clinically evident recurrence. For surveillance, this test is often obtained every 3 months.” 3 In addition, the guideline specifically references a Signatera publication with data from a prospective multicenter study published in 2024 in the Journal of Clinical Oncology (JCO). The study demonstrated excellent performance of Signatera, with 95% detection at time of enrollment and 20x higher risk of recurrence among patients who were persistently Signatera positive. Natera believes this positive update on MCC can set a precedent for the important role of ctDNA testing across other indications. “ Signatera tumor-informed ctDNA testing is a highly accurate and prognostic biomarker for surveillance of high- and low-risk patients with MCC to help determine imaging frequency,” said Lisa Zaba, M.D., Ph.D., associate professor of dermatology, director of the MCC multi-disciplinary clinic and member of the supportive oncodermatology group at the Stanford Cancer Center. MCC is a rare skin cancer (~3,000 patients diagnosed annually) which disproportionately affects the elderly with most patients diagnosed above age 70. 4 MCC has high mortality and a recurrence rate of 40% within 5 years. 5 “ These guideline changes came faster than expected given the typical timelines to be included,” said Alexey Aleshin, M.D., corporate chief medical officer and general manager of oncology for Natera. “ The inclusion of ctDNA testing in NCCN guidelines for these histologies is another step toward more personalized care for patients with cancer.” About Signatera Signatera is a personalized, tumor-informed, molecular residual disease test for patients previously diagnosed with cancer. Custom-built for each individual, Signatera uses circulating tumor DNA to detect and quantify cancer left in the body, identify recurrence earlier than standard-of-care tools, and help optimize treatment decisions. The test is available for clinical and research use and is covered by Medicare for patients with colorectal cancer, breast cancer, ovarian cancer, and muscle-invasive bladder cancer, as well as for immunotherapy monitoring of any solid tumor. Signatera has been clinically validated across multiple cancer types and indications, with published evidence in over 100 peer-reviewed papers. 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 validated by more than 250 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, 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, coverage and reimbursement determinations from third-party payers, or our expectations 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 NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Colon Cancer Version 1.2025. © National Comprehensive Cancer Network, Inc. 2025. All rights reserved. Accessed February 7, 2025. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Rectal Cancer Version 1.2025. © National Comprehensive Cancer Network, Inc. 2025. All rights reserved. Accessed February 7, 2025. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Merkel Cell Carcinoma Version 1.2025. © National Comprehensive Cancer Network, Inc. 2025. All rights reserved. Accessed January 17, 2025. American Cancer Society. Key statistics for Merkel Cell Carcinoma. https://www.cancer.org/cancer/types/merkel-cell-skin-cancer/about/key-statistics.html McEvoy AM, Lachance K, Hippe DS, et al. Recurrence and Mortality Risk of Merkel Cell Carcinoma by Cancer Stage and Time From Diagnosis. JAMA Dermatol. 2022;158(4):382-389.

AUSTIN, Texas,--( BUSINESS WIRE )-- Natera, Inc. (NASDAQ: NTRA), a global leader in cell-free DNA and genetic testing, announced new data from the randomized, Phase III CALGB (Alliance) / SWOG 80702 study. The study will be presented today, Jan. 25, 2025 as a late-breaking oral presentation at the 2025 American Society of Clinical Oncology’s Gastrointestinal Cancers Symposium (ASCO GI) in San Francisco, CA. This first-of-its-kind study evaluated whether Signatera-positive patients benefit from an escalation in adjuvant treatment. In the trial, Signatera was used to evaluate the benefit of adding celecoxib, a non-steroidal anti-inflammatory drug (NSAID), to standard of care (SOC) adjuvant chemotherapy with FOLFOX in the management of stage III colorectal cancer (CRC). The pre-specified analysis included approximately 1,000 patients with available post-surgical plasma samples, who were randomized to receive FOLFOX (+/-) celecoxib. Key findings included: Signatera-positivity after surgery was predictive of a disease-free survival (DFS) and overall survival (OS) benefit with the addition of celecoxib to adjuvant FOLFOX. The addition of celecoxib to SOC chemotherapy significantly improved DFS compared to placebo (HR 0.55, 95% CI 0.39-0.80; p=0.001) among Signatera-positive patients with a three-year DFS of 44.1% versus 26.6%. Similar results were seen for OS (HR 0.58, 95% CI 0.38-0.90; p=0.013). No survival benefit was seen by adding celecoxib to chemotherapy in Signatera-negative patients. Signatera status after surgery and prior to starting adjuvant therapy was highly predictive of recurrence. Signatera-positivity was significantly associated with worse DFS (HR 7.14, 95% CI: 5.54-9.21; p<0.0001) and OS (HR 6.72, 95% CI: 4.91-9.18; p<0.0001). “ The results from the CALGB (Alliance) / SWOG 80702 study mark an unprecedented moment in personalized medicine for patients with colorectal cancer,” said Alexey Aleshin, M.D., corporate chief medical officer and general manager of oncology for Natera. “ We demonstrated Signatera’s ability to predict a benefit in both disease-free survival and overall survival for Signatera-positive patients from the addition of celecoxib, an extremely accessible, affordable, and well-tolerated therapy. These data also offer compelling evidence to address an unmet need in adjuvant colorectal cancer treatment, where there has not been a new drug approval in over 20 years.” The results of the randomized, double-blind ALTAIR clinical trial will also be presented in a poster today. ALTAIR examined treatment escalation with Trifluridine/Tipiracil (FTD/TPI) in patients with stage I-IV colorectal cancer. In the trial, 243 Signatera-positive patients were randomized to FTD/TPI or placebo over a six-month treatment period. The results showed a trend toward benefit in the FTD/TPI group (median DFS of 9.3 months vs. 5.6 months in the placebo group), although it did not reach statistical significance (HR, 0.79; P = 0.107). There was a significant benefit for resected oligometastatic stage IV patients treated with FTD/TPI, showing a median DFS of 9.76 months as compared to 3.96 months in the placebo group (HR, 0.53; P = 0.012). This presents an opportunity for clinical benefit in stage IV patients who test positive for MRD. About Signatera Signatera is a personalized, tumor-informed, molecular residual disease test for patients previously diagnosed with cancer. Custom-built for each individual, Signatera uses circulating tumor DNA to detect and quantify cancer left in the body, identify recurrence earlier than standard-of-care tools, and help optimize treatment decisions. The test is available for clinical and research use and is covered by Medicare for patients with colorectal cancer, breast cancer, ovarian cancer, and muscle-invasive bladder cancer, as well as for immunotherapy monitoring of any solid tumor. Signatera has been clinically validated across multiple cancer types and indications, with published evidence in over 100 peer-reviewed papers. 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 validated by more than 250 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, 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 .