POLE

PRESS RELEASE 02/04/2025, 07:00 CEST Biocartis Announces Launch of the Brand-New Idylla™ POLE-POLD1 Mutation Assay Mechelen, Belgium, 02 April 2025 – Biocartis NV (“Biocartis”), an innovative molecular diagnostics company, is pleased to announce the launch of the brand-new Idylla™ POLE-POLD1 Mutation Assay (RUO1), a fully automated, real-time polymerase chain reaction (PCR) Assay designed for the detection of the hypermutated phenotype associated with mutations in POLE and POLD1. POLE and POLD1 are proteins that ensure proper DNA amplification. When these proteins malfunction due to pathogenic mutations, uncontrolled DNA replication occurs, leading to cancer. Mutations in POLE and POLD1 have been identified in endometrial cancers and beyond2,3. POLE-mutated endometrial cancers are considered a distinct subtype in the molecular classification of endometrial cancer samples, next to dMMR/MSI-H, p53abn and NSMP subtypes4. The Idylla™ POLE-POLD1 Mutation Assay, run on the Idylla™ Platform, qualitatively detects 17 point mutations in the POLE gene and one mutation in the POLD1 gene, enabling it to detect 99% of the known POLE and POLD1 pathogenic mutations in a single cartridge. Optimized for use with formalin-fixed, paraffin-embedded (FFPE) tissue specimens, the Idylla™ POLE-POLD1 Mutation Assay offers fast and accurate results, with a hands-on time of under 3 minutes and a turnaround time of approximately 95 minutes, enabling laboratories to go from sample to result in less than 2 hours. Sigurd F. Lax, Professor and Head of Department of General Hospital Graz II5, commented on the new Assay, stating: "The Idylla™ POLE-POLD1 Mutation Assay has the potential to provide an on-demand, fast, and accurate solution, making molecular testing in endometrial cancer samples easier and more accessible than ever.“ At the Association for Molecular Pathology (AMP) 2024 Annual Meeting, Biocartis (Barault et al., 20246) presented the results of a multi-center study to retrospectively detect POLE mutations in endometrial cancer tissue samples (cfr. Press Release 23 October 2024). More than 450 clinical samples were tested using a prototype version of the Idylla™ POLE-POLD1 Mutation Assay, comparing its accuracy against NGS, Sanger sequencing, and qPCR. This prototype study demonstrated 98.2% overall accuracy, highlighting the Assay’s potential. The Assay has since been further enhanced by incorporating additional POLE and POLD1 mutations, achieving a 99% mutation coverage with an impressive 97.2% positive percent agreement and 99.2% negative percent agreement. For more information about the newly available Idylla™ POLE-POLD1 Mutation Assay, please visit the Biocartis website or contact the Biocartis team. Roger Moody, Chief Executive Officer of Biocartis, commented: “We are pleased to introduce the Idylla™ POLE-POLD1 Mutation Assay, which empowers laboratories to streamline molecular profiling for endometrial cancer.” ----- END ----- More information: www.biocartis.com info@biocartis.com Biocartis NV. Generaal De Wittelaan 11B, 2800 Mechelen, Belgium About Biocartis With its revolutionary and proprietary Idylla™ Platform, Biocartis aspires to enable personalized medicine for patients around the world through universal access to molecular testing, by making molecular testing actionable, easy, fast and suitable for any lab. The Idylla™ Platform is a fully automated sample-to-result, real-time PCR (Polymerase Chain Reaction) based system designed to offer in-house molecular biomarker testing in only 3 hours, allowing fast and optimal treatment selection. ​Idylla™'s continuously expanding menu of molecular diagnostic tests and research assays addresses key unmet clinical needs. Today, Biocartis offers tests supporting lung, skin, thyroid, colorectal, endometrial, blood, brain and breast cancer. More information: www.biocartis.com. Follow us on LinkedIn, Facebook and X (Twitter). Disclaimers Idylla™ Platform is CE-marked in Europe in compliance with EU IVD Regulation 2017/746, listed as a class II device in the US under establishment registration 3009972873, and registered in many other countries. Idylla™ POLE-POLD1 Mutation Assay is for Research Use Only (RUO), not for use in diagnostic procedures. Biocartis and Idylla™ are registered trademarks in Europe, the US and many other countries. The Biocartis and Idylla™ trademarks and logos are used trademarks owned by Biocartis NV. © April 2025, Biocartis NV. All rights reserved. 1 For Research Use Only (RUO), not for use in diagnostic procedures.2 Barbari, S. R., & Shcherbakova, P. V. (2017). Replicative DNA polymerase defects in human cancers: Consequences, mechanisms, and implications for therapy. DNA repair, 56, 16–25. https://doi-org.libproxy1.nus.edu.sg/10.1016/j.dnarep.2017.06.0033 Ambrosini, M. et al. (2024). Immune checkpoint inhibitors for POLE or POLD1 proofreading-deficient metastatic colorectal cancer. Annals of Oncology, 35 (7), 643– 655. https://doi-org.libproxy1.nus.edu.sg/10.1016/j.annonc.2024.03.0094 Kommoss, S. et al. (2018). Final validation of the ProMisE molecular classifier for endometrial carcinoma in a large population-based case series. Annals of Oncology, 29(5). https://doi-org.libproxy1.nus.edu.sg/10.1093/annonc/mdy0585 Department of Pathology, Hospital Graz II, Graz, Austria & School of Medicine, Johannes Kepler University, Linz, Austria.6 Barault, L. et al (2024). The Idylla POLE Mutation Assay: A New Tool for Direct Mutation Detection from FFPE Tissue. The Journal of Molecular Diagnostics, 26(11), S139.

AUSTIN, Texas--( BUSINESS WIRE )-- Natera, Inc. (NASDAQ: NTRA), a global leader in cell-free DNA and genetic testing, today announced the enrollment of the first patients in the SAGITTARIUS clinical trial. Sponsored by The AIRC Institute of Molecular Oncology (IFOM-ETS) and funded by the European Union Horizon Europe Programme, SAGITTARIUS is a global, randomized, phase III clinical trial designed to evaluate the use of Signatera to guide personalized adjuvant treatment strategies for patients with colon cancer. The study aims to enroll approximately 700-900 stage III and high-risk stage II colon cancer patients following surgical resection. Signatera-positive patients will be randomized to receive either genotype-guided therapy tailored to their individual tumor mutational profile or six months of standard chemotherapy. The trial’s investigational arm will explore the potential of administering immunotherapy or targeted agents approved for metastatic colon cancer earlier in the disease course to increase the proportion of patients cured with adjuvant therapy. This genomically-driven approach will focus on mismatch repair status, POLE, RAS/RAF mutation status, and HER2 amplification status. For Signatera-negative patients, the trial will compare physician choice treatments with options for de-escalation to observation or single-agent capecitabine for six months. SAGITTARIUS includes collaborations with 9 partners in 5 countries in Europe, and a network of 26 clinical centers in Italy, Spain, and Germany. “ The enrollment of the first patients in SAGITTARIUS represents a significant milestone in a trial that has the potential to transform treatment approaches for colorectal cancer,” said Silvia Marsoni, MD, PhD, head of the precision oncology unit at IFOM ETS and scientific coordinator of the SAGITTARIUS Project. “ The trial aims to move beyond the traditional one-size-fits-all, post-surgical standard of care with chemotherapy by introducing a truly personalized treatment approach tailored to each patient,” said Adham Jurdi, MD, senior medical director of oncology at Natera. “ Signatera-positive patients will receive adjuvant therapies matched to their specific mutational profiles. Additionally, we are optimistic that the study will generate evidence to support the de-escalation of chemotherapy for Signatera-negative patients.” Clara Montagut, MD, PhD, head of the gastrointestinal cancer unit at Hospital del Mar in Barcelona, Spain, and principal investigator of the SAGITTARIUS clinical trial, further emphasized the study’s innovative goals, noting, “ We aim to anticipate the use of therapies tailored to the molecular landscape of the patient’s tumor, including immunotherapy and targeted therapies with proven efficacy in the metastatic setting within the adjuvant treatment context. To our knowledge, SAGITTARIUS is currently the only trial pursuing this approach in the field of liquid biopsy research.” About the SAGITTARIUS Horizon Europe project The SAGITTARIUS clinical trial is part of a wider effort, the SAGITTARIUS project, funded by the European Union Horizon Europe Programme. The SAGITTARIUS project, which also includes health cost and quality of life research to comprehensively assess the full cost-effectiveness of interventional liquid biopsy, aims to pave the way for more effective, tailored treatments that enhance both outcomes and quality of life for colon cancer patients, while potentially lowering the cost impact on private and public health systems and reducing treatment disparities. The SAGITTARIUS project is a collaboration of 9 partners in Italy, Spain, Germany, Belgium and Estonia. For more information, visit www.sagittarius-horizon.eu . About IFOM ETS IFOM ETS - the AIRC Institute of Molecular Oncology is a leading cancer research institute based in Milan, Italy, with international outreach in Japan. The institute, supported by the AIRC Foundation for Cancer Research, is focused on the study of cancer formation and development at molecular level, with a strong emphasis on rapidly translating research findings into clinical benefit for cancer patients. With the expertise in trial design and management of its Precision Oncology Unit, IFOM is the sponsor of the SAGITTARIUS clinical trial and the coordinator of the homonymous Horizon Europe project. For more information, visit www.ifom.eu/en/ . 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 .

PRESS RELEASE - 23/10/2024, 07:00 CEST Biocartis announces six Idylla™ abstracts to be presented at AMP 2024 Annual Meeting Mechelen, Belgium, 23 October 2024 – Biocartis NV (“Biocartis”), an innovative molecular diagnostics company, is pleased to announce that six abstracts highlighting the benefits of Idylla™ will be presented at the Association for Molecular Pathology (AMP) Annual Meeting, taking place November 19th to November 23rd, 2024 in Vancouver, Canada. In addition, Biocartis will host a free corporate workshop. Six Idylla™ abstracts from renowned institutions will be presented at this year's AMP conference, showcasing the strong collaborations Biocartis has built with leading research and academic partners. 1. Performance Assessment and Clinical Validation of the Idylla™ IDH1-2 Mutation Assay Kit in Rapid Detection of IDH Mutations in Acute Myeloid Leukemia Ashutosh Vashisht, Ashis K Mondal, Lora Walczak, Vishakha Vashisht, Shubha Sharma, Pankaj Ahluwalia, Jana Woodall, Harmanpreet Singh, Ravindra Kolhe - Department of Pathology, Medical College of Georgia, Augusta University, GA, USA. By using 36 samples from 18 unique AML cases, the authors were able to demonstrate perfect concordance (100%) of the Idylla™ IDH1-2 Mutation Assay Kit with NGS. Directly using bone marrow aspirate in the Cartridge significantly reduced turnaround time, making this technique an ideal solution for developing assays for AML diagnosis, prognosis, and treatment evaluation. 2. The Idylla™ Platform Enables Rapid and Accurate EGFR Mutation Assessment in NSCLC with Minimal Sample InputKatherine Drews-Elger, Rodrigo Santoscoy-Valencia, Catherine Garcia-Serje, Silvia Gonzalez-Leiva, Mayra Rodriguez, Orlando Bracho-Rincon, and Roberto Ruiz-Cordero - Department of Pathology and Laboratory Medicine, University of Miami, Miami, FL - Jackson Memorial Hospital, Miami, FL - Clinical OncoMolecular Lab, Department of Pathology and Laboratory Medicine, University of Miami, Miami, FL. This new prospective study demonstrated how the Idylla™ EGFR Mutation Assay offered rapid and accurate detection of EGFR mutations in non-small cell lung cancer (NSCLC), with 95% concordance with NGS. The Assay successfully identified mutations in cases where NGS could not be performed (10% of the cohort) and reduced turnaround time from 12.1 to 1.7 days. With minimal sample requirements and hands-on time, Idylla™ provided a faster option for obtaining EGFR mutation status in NSCLC. 3. Re-verification and Report Ruling Revision of NTRK Fusion Results of Idylla™ GeneFusion Assay after Manufacturer Algorithm UpdatePatricia Caffes, Gang Zheng M.D. Ph.D., Ying-Chun Lo M.D. Ph.D. - Division of Laboratory Genetics and Genomics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN - Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN. This recent re-verification study of the Idylla™ GeneFusion Assay demonstrated improved sensitivity for detecting NTRK2 fusions, due to a software update. Although sensitivity for NTRK3 decreased slightly, updates to the laboratory’s standard operating procedure have enhanced accuracy by requiring confirmation testing for certain equivocal results. The study showed no changes to the detection of ALK, ROS1, RET, and MET fusions, maintaining 100% sensitivity and specificity. 4. Rapid Determination of IDH1 and IDH2 Mutation Status in AML and Glioma Using Microfluidic Detection SystemCatalina Esguerra, Anthony Magliocco - Protean BioDiagnostics This study showed 97% accuracy, 100% sensitivity and 95% specificity for detecting IDH1 and IDH2 mutations in glioma and AML samples with the Idylla™ IDH1-2 Mutation Assay Kit. The Assay delivered rapid results within 95 minutes, with only one discordant case under investigation, potentially due to a higher sensitivity than the reference test. The Idylla™ System was praised for its ease of use and reliability, making it a valuable tool for determining IDH mutation status in various malignancies. 5. The Idylla™ POLE Mutation Assay, a New Tool for Direct Mutation Detection from FFPE TissueSofie Metsu - Biocartis Based on a literature review, the diagnostic sensitivity of the (under development) Idylla™ POLE Mutation Assay for detecting POLE mutations with evidence to support clinical utility, was 98% in endometrial cancer and 90% colorectal cancer. The new assay is currently undergoing evaluation at multiple selected sites across Europe and the US, using clinical endometrial carcinoma FFPE specimens. The conclusive results will be shared at the AMP conference. 6. Same-Day Molecular Testing Results from Cytology Specimens: The Next Frontier of the Rapid On-site Evaluation?Dr. Gloria Sura - Cytology, MDACC This MDACC study demonstrated the feasibility of Idylla™ for rapid and accurate molecular testing of NSCLC and thyroid cancer biomarkers from cytology samples. Results were available in 2-3 hours, with high accuracy across KRAS, EGFR, BRAF and GeneFusion Assays, showing concordance rates of 94-100%. The Biocartis corporate workshop will take place on November 20th, 2024 at 3 PM PST and is focused on optimizing Fine Needle Aspiration (FNA) workflows using the Idylla™ Platform. Gloria Sura, MD (MD Anderson Cancer Center) will present a comprehensive feasibility and performance study showcasing the rapid assessment of EGFR, KRAS, BRAF and GeneFusion in cytopathology. Dr. Sura will highlight the integration of cytology and small biopsy specimens, particularly in lung and thyroid cancers, within a large cancer center. W. Michael Korn, M.D., Chief Medical and Scientific Officer of Biocartis, commented: “The research results that will be presented at the AMP Annual Meeting, highlight our commitment to expanding rapid and high-quality testing options for patients with hematological and solid malignancies. Our Idylla™ System allows for the analysis of small biological samples, including cytological specimens, providing healthcare providers with critical information for timely treatment decisions within hours.” ----- END ----- More information: www.biocartis.com info@biocartis.com About Biocartis With its revolutionary and proprietary Idylla™ Platform, Biocartis aspires to enable personalized medicine for patients around the world through universal access to molecular testing, by making molecular testing actionable, convenient, fast and suitable for any lab. The Idylla™ Platform is a fully automated sample-to-result, real-time PCR (Polymerase Chain Reaction) based system designed to offer in-house access to accurate molecular information in a minimum amount of time for faster, informed treatment decisions. Idylla™'s continuously expanding menu of molecular diagnostic tests addresses key unmet clinical needs, with a focus in oncology. This is the fastest growing segment of the molecular diagnostics market worldwide. Today, Biocartis offers tests supporting melanoma, colorectal, lung, breast, thyroid, brain, blood and liver cancer. More information: www.biocartis.com. Follow us on X (Twitter): @Biocartis. Idylla™ IDH1-2 Mutation Assay Kit, Idylla™ EGFR & POLE-POLD1 Mutation Assay, and Idylla™ GeneFusion Assay are for Research Use Only (RUO), not for use in diagnostic procedures. Idylla™ POLE-POLD1 Mutation Assay is currently under development. Idylla™ Platform is CE-marked in Europe in compliance with EU IVD Regulation 2017/746, listed as a class II device in the US under establishment registration 3009972873, and registered in many other countries. Biocartis and Idylla™ are registered trademarks in Europe, the United States and other countries. The Biocartis and Idylla™ trademark and logo are used trademarks owned by Biocartis. Please refer to the product labeling for applicable intended uses for each individual Biocartis product. © October 2024, Biocartis NV. All rights reserved.