Prospera™ precision— from the experts of cell-free DNA testing

New! From Natera Covered by Medicare Introducing Prospera

Prospera is powered by highly optimized, proprietary cell-free DNA (cfDNA) technology. As part of your tool kit, Prospera assesses all types of kidney transplant rejection2 with great precision.1,3

Covered by Medicare for all kidney transplant recipients

Simpler and less invasive than biopsy

More sensitive and specific than current assessment tools across all types of rejection2,4,5

Up to 5x less variability than first-generation donor-derived cell-free DNA technology1,3 The need for something better. Experts in cell-free DNA. For transplant clinicians treating, monitoring and managing patients across the entire transplant continuum— Optimized for transplantation. To improve the management of organ transplantation, , and reproductive health, Natera is the goal is earlier, accurate detection of rejection that harnessing the power of cfDNA from a single blood sample and a methodology that uses single-nucleotide enables treatment to promote longer graft life. polymorphisms (SNPs) for non-invasive testing.

Current tools to monitor rejection are limited as they risk detecting rejection late or not at all, Optimized Organ Transplantation platform which often leads to chronic active antibody-mediated rejection (ABMR) and eventual graft Highest performing dd-cfDNA test failure. The lack of an effective tool to identify clinical and subclinical antibody-mediated and T cell-mediated rejection (TCMR) presents a critical challenge to the clinician. Applied Oncology experience First custom-built circulating-tumor DNA test

Built Women’s Health foundation Pioneered SNP-based technology to a broad prenatal-testing product suite

TRANSPLANT PATIENT CARE TOOLKIT An established methodology using a validated biomarker Cell-free DNA (cfDNA) technology is an established methodology in prenatal, oncology and transplantation applications.3,5,7-12 Further, cfDNA is a proven biomarker in kidney and heart transplantation 1-5,7,13-17 for identifying active rejection.

Serum Donor-specific Prospera creatinine antibodies Biopsy transplant tests (DSA) assessment Applying proven cell-free DNA experience to assess kidney injury From a single blood draw, Prospera measures the amount of donor DNA from the transplanted kidney in the patient’s blood. This will help you and your care team assess all types of rejection more precisely than available standard assessment tools.

HOW PROSPERA WORKS

Recipient Blood Sample Precise Identification Interpretation Current baseline Often late indicator Infrequently used Non-invasive, Donor screening standard, of active rejection, due to cost, potential optimized cfDNA NO active rejection: Minimal donor-derived cell-free yet are not specific may indicate patients complications, technology that is C T A DNA (dd-cfDNA) is released in a G A T or sensitive enough that are at higher risk interpretation highly accurate in stable patient’s blood. for allograft rejection2 for rejection6 challenges and assessing all types patient discomfort of active rejection SNP difference OR

Active rejection: T T A Upon cell injury, more dd-cfDNA A A T is released from the donor kidney.

Recipient

Mix of donor and recipient 13,000 single-nucleotide polymorphisms Prospera reports the percentage of dd-cfDNA cell-free DNA (cfDNA) (SNPs) and advanced are used in a transplant recipient’s blood to differentiate recipient and donor cfDNA

PERSONALIZED ASSESSMENT

Patient Test Summary

Establish a personalized dd-cfDNA baseline to 0.6% determine a normal-state dd-cfDNA of the patient’s new kidney 4 Track dd-cfDNA 0.5% levels over time

0.4%

Date of blood draw

T1 T2 T3 T4 T5 T6 T7 Oct 2, 2019 Nov 4, 2019 Dec 5, 2019 Jan 7, 2020 Mar 5, 2020 Jun 4, 2020 Sep 7, 2020 Now—catch ALL rejection types in a single blood draw Prospera’s unique ability to identify both ABMR and TCMR gives Lower risk of missing active rejection a comprehensive view of your patient’s rejection status. With 95% negative predictive value (NPV), Prospera misses nearly HIGHLY SENSITIVE TO IDENTIFY ALL TYPES OF REJECTIONS 1 3 three times fewer rejections than serum creatinine.2 COMPARISON OF NPV FROM PUBLISHED VALIDATION STUDIES Based upon 25% prevalence of active rejection 2 10.0 14% missed

NPV: 86%

2 1.0 Serum creatinine 5% missed dd-cfDNA Level (%) ~3x NPV: 95% fewer rejections 0.1 Unparalleled missed Prospera2 ABMR ABMR ABMR bABMR TCMR (3) bTCMR TCMR TCMR (8) (13) (12) (2) precision. Prospera can assist in the decision to rule out active rejection before considering ABMR/TCMR the necessity of a biopsy.2

Assessing for ABMR and cell-mediated rejection enables clinicians to have a Optimized by more comprehensive understanding for earlier, timely coordination of clinical management and a chance to save a patient’s kidney.

0.66% More sensitive and specific than standard Range of first-generation dd-cfDNA Prospera.

Range of Prospera screening tools

Actual 0.61% In a published clinical validation, Prospera demonstrated better .6 Highly accurate in both surveillance0.6% 0.59% performance in correctly classifying patients with active rejection— 2 including TCMR.2 Serum creatinine may incorrectly classify and for-cause settings up to 1 out of 2 patients experiencing active rejection as normal.2 0.54% 2 4 Prospera is the first cfDNA assay to publish performance in surveillance situations. OF 100 ACTIVE REJECTION CASES, THE NUMBER OF PATIENTS WHO WOULD BE MISSED

SIMILAR% of dd-cfDNA PERFORMANCE IN STABLE AND THOSE WITH CLINICAL SIGNS OF REJECTION Using a 1% dd-cfDNA threshold

Active rejection Sensitivity Negative predictive value* Serum creatinine2

Actual Clinical AR 0.4% 86% 93.8% 48/100 .4 Sensitivity: 52% Subclinical AR 92% 98.3%** Prospera2

*Assuming 25% AR Prevalence (higher risk population) **Assuming 10% AR Prevalence (low risk population) 11/100 Date of T1 T2 Sensitivity: 89% blood draw Oct 2, 2019 Nov 4, 2019

Using Prospera in a surveillance setting can enable clinicians to effectively manage transplant Prospera provides confident results to reassure you in your clinical care decisions when managing patients with unsuspected, subclinical rejection as a way to increase the longevity of their kidney.2 your transplant patients. Patients first. Partners always. Pledging ongoing support and resources for seamless integration into your clinical workflow.

Natera partners with you to enable your team for: • Easy ordering • Convenient blood draw options • Transparent tracking • Results at your fingertips • Dedicated support at every step

PATIENT: Sherry Finley DOB: 7/8/1987 OCCUPATION: Teacher How we enable you: ProsperaLink Program cfDNA Results: 0.28% Your concierge team of Natera clinical experts to help you and your transplant 0.8% care team at every step of the way. 0.7% 0.6% MEDICAL SCIENCE NURSE PATIENT 0.5% LIAISON COORDINATOR COORDINATOR 0.4% 0.3%

Time post-transplant

• Monthly case reviews • Kit fulfillment • Scheduling of patient blood draws • ProActive registry study • Portal set up and troubleshooting • Billing and logistical • Educational programs support for patients • Call Out Program (if result >1%) • Shipping logistics

Natera welcomes all insurances. Prospera is covered by Medicare for assessing potential kidney transplant rejection. The goal of Natera’s billing department is to make the process transparent and easy for our patients. In the rare event your patient has financial responsibility for Prospera, Natera offers flexible financial assistance programs and will work closely with your patient to ensure there is no hardship on them or their family.

In all cases, the Natera team is here to help you, your staff, and your patients with any billing or reimbursement questions and needs at +1 650.273.4468. Simplified for you, along every step. Protect every patient’s life with best-in-class care to live long and prosper

Optimized surveillance for ction Access rering eslts Next teps even more confident results Learn from our clinical Offer to all kidney Easily order via paper, Monitor orders, access Track dd-cfDNA team through transplant patients, online portal or EMR actionable report levels over time after Precise cell-free DNA testing from the experts informational sessions, including those and exible blood draw supplements and establishing a on-demand videos, covered by Medicare options including share with the broader personalized baseline to webinars and online mobile phlebotomy transplant care team determine “normal state” learning materials of a patient’s new kidney

References 1 Altug Y, Liang N, Ram R, et al. Analytical validation of a single-nucleotide polymorphism-based donor-derived cell-free DNA assay for detecting rejection in kidney transplant patients. Transplantation, 2019 2 Sigdel TK, Archila FA, Constantin T, et al. Optimizing detection of kidney transplant injury by assessment of donor-derived cell-free DNA via massively multiplex PCR. J Clin Med. 2019;8(1):19. 3 Grskovic M, Hiller DJ, Eubank LA, et al. Validation of a clinical-grade assay to measure donor-derived cell-free DNA in solid organ transplant recipients. J Mol Diagn. 2016;18(6):890-902. 4 Bromberg JS, Brennan DC, Poggio E, et al. Biological variation of donor-derived cell-free DNA in renal transplant recipients: clinical implications. J Appl Lab Med. 2017;2(3):309-321. 5 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. doi: 10.1681/ASN.2016091034. 6 Cooper J, Gralla J, Cagle L. Inferior Kidney Allograft outcomes in Patients With De Novo Donor-Specific Antibodies Are Due to Acute Rejection Episodes. Transplantation 2001;91: 1103-1109 7 Snyder, et al. Universal noninvasive detection of solid organ transplant rejection. Proc. Natl. Acad. Sci. USA 2011, 108, 6229 - 6234 8 Palomaki, et al. DNA sequencing of maternal plasma to detect : an international clinical validation study. Genet Med. 2011 Nov;13(11):913-20 9 Sparks, et al. Noninvasive prenatal detection and selective analysis of cell-free DNA obtained from maternal blood: evaluation for trisomy 21 and trisomy 18. Am J Obstet Gynecol. 2012, 206, P319.E1 - 319.E9 10 Newman, et al. An ultrasensitive method for quantitating circulating tumor DNA with …. Nat Med 2014, 2014 May;20(5):548-54 11 Pergament, et al. Single-nucleotide polymorphism-based noninvasive prenatal screening in a high-risk and low-risk cohort. Obstet. Gynecol. 2014, 124 Pt 1, 210 - 218 12 Abbosh, et al. Phylogenetic ctDNA analysis depict early-stage lung cancer evolution. Nature 2017, 545, 446 - 451 13 Lo, et al. Biomarkers for kidney transplant rejection. Nat. Rev. Nephrol. 2014, 10, 215 - 225 14 Beck, et al. Digital droplet PCR for rapid quantification of donor DNA in the circulation of transplant recipients as a potential universal biomarker of graft injury. Clin. Chem. 2013, 59, 1732-1741 15 De Vlaminck, et al. Circulating cell-free DNA enables noninvasive diagnosis of heart transplant rejection. Sci. Transl. Med. 2014, 6, 241ra77 16 Hidestrand, et al. Highly sensitive noninvasive cardiac transplant rejection monitoring using targeted quantification of donor-specific cell-free deoxyribonucleic acid. J Am Coll Cardiol. 2014;63(12):1224–1226. doi:10.1016/j.jacc.2013.09.029 17 Huang, et al. Early clinical experience using donor‐derived cell‐free DNA to detect rejection in kidney transplant recipients. Transplantation. 2019, doi: 10.1111/ajt.15289. Only from Natera

Our mission is to improve disease management for patients worldwide. We have been exploring and evolving our expertise in cell-free DNA (cfDNA) across women’s health, oncology and organ transplant care. We founded our company to use the most innovative technology for earlier detection of genetic conditions in pregnancies. In the years since, we have helped nearly two million families on their path to parenthood with solutions that tell them about the genetic health of their babies.

Built on Natera’s pioneering technology, our first circulating tumor DNA (ctDNA) test is custom-built and personalized for each cancer patient. Now, we have refined our technology to assess tiny amounts of donor DNA in the blood of kidney transplant patients. And that’s just the start.

With all the rapid advances taking place in cfDNA at Natera, there is one constant: our unwavering commitment to patients.

2M+ 100+ 90 CAP CLIA cfDNA tests clinicians, PhD’s, countries accredited certified performed and scientists worldwide

201 Industrial Road, Suite 410, San Carlos, CA 94070 | Main +1 650.249.9090 | Fax +1 650.730.2272 | natera.com

The test described has been developed and its performance characteristics determined by the CLIA-certified laboratory performing the test. The test has not been cleared or approved by the US Food and Drug Administration (FDA). Although FDA has generally not enforced the premarket review and other FDA legal requirements for laboratory-developed tests in the US, certification of the laboratory is required under CLIA to ensure the quality and validity of the tests. CAP accredited, ISO 13485, and CLIA certified. © 2020 Natera, Inc. All Rights Reserved. PRO_BR_CommNeph_20200416_NAT-8020141

Learn more about Prospera: Call us +1 650.273.4468 Visit us natera.com/prospera