Renal transplant rejection

Designation is based on data from the clinical development program which demonstrated clinical proof of conceptFelzartamab, an investigational anti-CD38 monoclonal antibody, is a potential first-in-class therapeutic candidate for a range of rare immune-mediated indications with planning underway for Phase 3 developmentFDA Breakthrough Therapy Designation is intended to expedite the development and review of drugs for serious or life-threatening conditions and which have potential to show substantial improvement over existing therapies CAMBRIDGE, Mass., Oct. 09, 2024 (GLOBE NEWSWIRE) -- Biogen Inc. (Nasdaq: BIIB) – Biogen announced today that felzartamab, an investigational anti-CD38 monoclonal antibody, has received Breakthrough Therapy Designation (BTD) from the U.S. Food and Drug Administration (FDA) for the treatment of late antibody-mediated rejection (AMR) without T-cell mediated rejection in kidney transplant patients. The FDA grants BTD to drug candidates for serious or life-threatening conditions and that have preliminary clinical evidence demonstrating potential to provide substantial improvement over existing therapies. The designation provides additional opportunities to engage the FDA and to support the drug development program through Fast Track designation features. Data from the clinical development program that supported the designation were published in the New England Journal of Medicine and presented as a late-breaking presentation at the 61st European Renal Association (ERA) Congress in Stockholm, May 2024. "Antibody-mediated rejection is a major reason why kidney transplants fail, and currently patients suffering from AMR have tremendous unmet medical need,” said Travis Murdoch, Head of HI-Bio at Biogen. “We are focused on tackling this important challenge, and the breakthrough therapy designation will enable us to work efficiently with the FDA to accelerate development of felzartamab in AMR.” Felzartamab previously received BTD and Orphan Drug Designation (ODD) from the FDA for development in the treatment of primary membranous nephropathy (PMN) and ODD in the treatment of AMR in kidney transplant recipients. Phase 2 studies have been completed in AMR, PMN and IgA nephropathy (IgAN). Biogen plans to initiate Phase 3 trials for felzartamab across AMR, IgAN, and PMN in 2025. Biogen acquired Human Immunology Biosciences (HI-Bio) in July 2024. About FelzartamabFelzartamab is an investigational therapeutic human monoclonal antibody directed against CD38, a protein expressed on mature plasma cells. Felzartamab has been shown in clinical studies to selectively deplete CD38+ plasma cells, which may allow applications that ultimately improve clinical outcomes in a broad range of diseases driven by pathogenic antibodies. Felzartamab was originally developed by MorphoSys AG for multiple myeloma. HI-Bio exclusively licensed the rights to develop and commercialize felzartamab across all indications in all countries and territories excluding China (including Macau and Hong Kong and Taiwan). Felzartamab is an investigational therapeutic candidate that has not yet been approved by any regulatory authority and its safety and effectiveness have not been established. About Antibody-Mediated Rejection (AMR) in Kidney Transplant RecipientsAntibody-mediated rejection (AMR) is a major cause of kidney transplant failure, with chronic AMR affecting ~12% of patients that receive kidney transplants annually in the U.S.1 AMR has emerged as the leading cause of late graft loss in kidney transplant recipients. Effective treatment options for chronic AMR are currently limited.2 About BiogenFounded in 1978, Biogen is a leading biotechnology company that pioneers innovative science to deliver new medicines to transform patients’ lives and to create value for shareholders and our communities. We apply deep understanding of human biology and leverage different modalities to advance first-in-class treatments or therapies that deliver superior outcomes. Our approach is to take bold risks, balanced with return on investment to deliver long-term growth. We routinely post information that may be important to investors on our website at www.biogen.com. Follow us on social media - Facebook, LinkedIn, X, YouTube. Biogen Safe Harbor This news release contains forward-looking statements, including related to the potential clinical effects of felzartamab; the potential benefits, safety and efficacy of felzartamab; the clinical development program for felzartamab; the identification and treatment of AMR; our research and development program for the treatment of AMR; the potential of our commercial business and pipeline programs, including SPINRAZA; and risks and uncertainties associated with drug development and commercialization. These forward-looking statements may be accompanied by words such as “aim,” “anticipate,” “believe,” “could,” “estimate,” “expect,” “forecast,” “intend,” “may,” “plan,” “potential,” “possible,” “will,” “would” and other words and terms of similar meaning. Drug development and commercialization involve a high degree of risk, and only a small number of research and development programs result in commercialization of a product. Results in early-stage clinical trials may not be indicative of full results or results from later stage or larger scale clinical trials and do not ensure regulatory approval. You should not place undue reliance on our forward-looking statements. These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements, including without limitation, uncertainty of success in the development and potential commercialization of SPINRAZA; the risk that we may not fully enroll our clinical trials or enrollment will take longer than expected; unexpected concerns may arise from additional data, analysis or results obtained during our clinical trials; regulatory authorities may require additional information or further studies, or may fail or refuse to approve or may delay approval of our drug candidates, including SPINRAZA; the occurrence of adverse safety events; the risks of unexpected hurdles, costs or delays; failure to protect and enforce our data, intellectual property and other proprietary rights and uncertainties relating to intellectual property claims and challenges; product liability claims; results of operations and financial condition. The foregoing sets forth many, but not all, of the factors that could cause actual results to differ from our expectations in any forward-looking statement. Investors should consider this cautionary statement, as well as the risk factors identified in our most recent annual or quarterly report and in other reports we have filed with the U.S. Securities and Exchange Commission. These statements speak only as of the date of this news release. We do not undertake any obligation to publicly update any forward-looking statements. References: Schinstock et al. (2018) Kidney Transplant with Low Levels of DSA or Low Positive B-Flow Crossmatch: An Underappreciated Option for Highly-Sensitized Transplant Candidates (Page 8). Available at: https://www-ncbi-nlm-nih-gov.libproxy1.nus.edu.sg/pmc/articles/PMC5481511/pdf/nihms837168.pdf#page=8 ; Ciancio et al. 2018 Antibody-Mediated Rejection Implies a Poor Prognosis in Kidney Transplantation: Results From a Single Center. Available at: https://onlinelibrary-wiley-com.libproxy1.nus.edu.sg/doi/10.1111/ctr.13392Rodriguez-Ramirez et al. 2022 Antibody-mediated rejection: prevention, monitoring and treatment dilemmas (Page 1). Available at: https://www-ncbi-nlm-nih-gov.libproxy1.nus.edu.sg/pmc/articles/PMC9475491/ MEDIA CONTACT:Jack Cox+ 1 781 464 3260public.affairs@biogen.comINVESTOR CONTACT:Stephen Amato+1 781 464 2442IR@biogen.com

Donor Quantity Score (DQS) technique is unique to Natera, improving detection of both acute cellular rejection and antibody-mediated rejection AUSTIN, Texas--(BUSINESS WIRE)-- Natera, Inc. (NASDAQ: NTRA), a global leader in cell-free DNA (cfDNA) and genetic testing, today announced the launch of Prospera Heart™ with Donor Quantity Score (DQS), further enhancing Prospera’s ability to detect rejection in heart transplant patients. Traditionally, donor-derived cell-free DNA (dd-cfDNA) tests have reported rejection risk based only on the fraction of dd-cfDNA in the blood vs. the total cfDNA (dd-cfDNA %). This fraction can be confounded by fluctuations in the amount of background total cfDNA (the denominator), which are sometimes caused by factors unrelated to the health of the transplant, including infection, surgery, or chemotherapy. Prospera Heart now incorporates a second metric – the DQS – that normalizes for the background total cfDNA. Prospera Heart with DQS combines the traditional donor fraction and the new DQS into a two-threshold algorithm, delivering a single result with more accurate risk assessment for both antibody mediated rejection (AMR) and acute cellular rejection (ACR). “Over the last two decades, Natera has pioneered cfDNA testing across women’s health, oncology, and transplant medicine,” said Michael Olymbios, M.D., Medical Director, Heart Transplant. “Our extensive experience with cfDNA and Natera’s culture of continuous innovation drove us to further refine Prospera Heart by introducing this two-threshold algorithm to better serve the transplant community.” A study performed at the University of Utah and the University of California San Diego showed that incorporating DQS enhanced the performance of Prospera Heart in screening for biopsy-proven active rejection. In an initial analysis of 703 plasma samples, the two-threshold algorithm, as compared to the traditional dd-cfDNA % alone, improved several key performance metrics as follows: Sensitivity increased from 80.0% to 88.2% Specificity increased from 76.1% to 84.2%, reducing false positive results by 37.5% Increased negative predictive value (NPV) from 97.4% to 98.6% The study was presented at The International Society for Heart and Lung Transplantation’s annual meeting in April 2024, and it will be submitted for peer-reviewed publication later this year. “The initial findings from our study indicate that DQS complements donor fraction and provides a clearer picture of rejection risk for the patient, compared to donor fraction alone,” said Josef Stehlik, M.D., M.P.H., Medical Director of the Heart Transplant Program and Co-chief of the Advanced Heart Failure Program at the University of Utah Hospital. “We believe this innovative technique can lead to fewer unnecessary biopsies and follow-up procedures for heart transplant recipients given the increase in sensitivity.” A similar two-threshold dd-cfDNA test for assessing the risk of kidney transplant rejection, Prospera Kidney with Quantification, was published in the Journal of the American Society of Nephrology1 and has been offered by Natera for kidney transplant patients since 2021. 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 validated by more than 200 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 . 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, or our expectations 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 and . References Bunnapradist S, Homkrailas, P, Ahmed, E, et al. Using both the fraction and quantity of donor-derived cell-free DNA to detect kidney allograft rejection, J Amer Soc Nephrology 2021; 32(10): 2439-2441.

Surveillance Monitoring with Both AlloSure Kidney and the AlloView AI-Enabled Risk Prediction Model Improves the Detection of All Types of Allograft Rejection AlloSure Kidney Detected Subclinical Rejection in Clinically Stable Patients and AlloSure Kidney dd-cfDNA Levels were Elevated Prior to Biopsy Proven Rejection in an Analysis of Patients Receiving Consecutive Biopsies AlloSure dd-cfDNA Levels Declined in Response to Immunosuppression Treatment Suggesting There May be Utility in Therapy Monitoring for Recovery or Progression BRISBANE, Calif.--(BUSINESS WIRE)-- CareDx, Inc. (Nasdaq: CDNA) – The Transplant Company™ focused on the discovery, development, and commercialization of clinically differentiated, high-value healthcare solutions for transplant patients and caregivers – today announced in conjunction with the 2024 American Transplant Congress, the publication in Nature Medicine1 of findings from the largest, real-world study of its kind, assessing the role of AlloSure® donor-derived cell-free DNA (dd-cfDNA) and of an AI-enabled rejection risk prediction model, AlloView™ that incorporates AlloSure to improve detection, characterization, and treatment of kidney allograft rejection. “This landmark study in Nature Medicine further establishes the clinical utility of AlloSure Kidney and the added value of AlloView, our AI-enabled risk prediction model, in detecting the presence, activity and severity of allograft rejection. These findings contribute to a growing body of evidence establishing new standards globally in the routine monitoring of rejection and treatment response in kidney transplant patients," said John W. Hanna, President & CEO of CareDx. The international multicenter study of 2,882 patients with AlloSure Kidney dd-cfDNA levels and matched biopsy results was conducted by the Paris Institute for Transplantation and Organ Regeneration along with researchers in the U.S. and Belgium. The study evaluated AlloSure Kidney and used AlloView, an AI-enabled risk prediction model, to predict rejection by combining AlloSure with standard of care measures, including estimated glomerular filtration rate (eGFR), proteinuria, change in serum creatinine, donor-specific antibodies (DSA), and previous history of rejection. The study results published in Nature Medicine demonstrated the following1: Surveillance monitoring with AlloSure Kidney and AlloView improves the detection of antibody-mediated rejection (ABMR), T-cell mediated rejection (TCMR), and subclinical rejection when compared to standard of care measures. AlloSure Kidney detected subclinical rejection in clinically stable patients. AlloSure Kidney dd-cfDNA levels were elevated prior to biopsy proven rejection in an analysis of patients receiving consecutive biopsies. AlloSure Kidney dd-cfDNA levels were associated with stability in patients with immune quiescence, a significant increase for patients with de novo allograft rejection, a significant decrease for patients with successfully treated rejection, and remained at elevated levels for patients with persistent allograft rejection. In patients with acute rejection, AlloSure Kidney dd-cfDNA levels were associated with the severity of acute rejection. “This study underscores AlloSure dd-cfDNA’s role as a real-time indicator of kidney transplant rejection, enabling clinicians to intervene earlier before rejection occurs and to monitor post-treatment progress without resorting to unnecessary biopsy procedures,” said Alexandre Loupy, MD, PhD, Professor of Nephrology and Statistics at Necker Hospital, and Director of the Paris Institute of Transplantation and Organ Regeneration at the French National Institute of Health (Inserm). CareDx’s AlloSure dd-cfDNA was made commercially available in 2017, the industry’s first dd-cfDNA for use to non-invasively identify the risk of allograft injury and rejection in kidney transplantation. Since then, AlloSure has also become available for clinical use in heart and lung transplant recipients. AlloView, an AI-enabled risk prediction model is now commercially available. AlloView optimizes patient risk prediction by integrating artificial intelligence, AlloSure and standard of care measures.2 About CareDx – The Transplant Company CareDx, Inc., headquartered in Brisbane, California, is a leading precision medicine solutions company focused on the discovery, development, and commercialization of clinically differentiated, high-value healthcare solutions for transplant patients and caregivers. CareDx offers testing services, products, and digital healthcare solutions along the pre- and post-transplant patient journey; and is the leading provider of genomics-based information for transplant patients. For more information, please visit: . Forward-Looking Statements This press release includes forward-looking statements related to CareDx, Inc., including statements regarding the potential benefits and results that may be achieved with AlloSure and AlloView. These forward-looking statements are based upon information that is currently available to CareDx and its current expectations, speak only as of the date hereof, and are subject to risks and uncertainties that could cause actual results to differ materially from those projected, including risks that CareDx does not realize the expected benefits of AlloSure and AlloView; risks that the findings in the Nature Medicine study supporting the data may be inaccurate; general economic and market factors; and other risks discussed in CareDx’s filings with the SEC, including the Annual Report on Form 10-K for the fiscal year ended December 31, 2023 filed by CareDx with the SEC on February 28, 2024, the quarterly report on Form 10-Q for the quarter ended March 31, 2024 filed by CareDx with the SEC on May 9, 2024, and other reports that CareDx has filed with the SEC. Any of these may cause CareDx’s actual results, performance, or achievements to differ materially and adversely from those anticipated or implied by CareDx’s forward-looking statements. CareDx expressly disclaims any obligation, except as required by law, or undertaking to update or revise any such forward-looking statements. References Aubert, O., Ursule-Dufait, C., Brousse, R., et al. Cell-Free DNA for the detection of kidney allograft rejection. Nat Med (2024). AlloView is intended to support the healthcare provider’s independent assessment of the patient’s post-transplant status. AlloView is not intended to diagnose a condition or determine a patient’s course of treatment. An AlloSure dd-cfDNA test result is a required input of AlloView. View source version on businesswire.com: Contacts CareDx, Inc. Media Relations Anna Czene 818-731-2203 aczene@caredx.com Investor Relations Greg Chodaczek investor@CareDx.com Source: CareDx, Inc. View this news release online at: