Company News from January to March 2022

Landmark ADMIRAL Study Clinically Validates AlloSure^® Kidney for Routine Organ Transplant Surveillance

Results from this large, multicenter prospective study published in Kidney International demonstrate that AlloSure Kidney is an early and accurate measure of allograft injury in routine organ transplant surveillance and is able to predict long-term graft survival outcomes.¹

The ADMIRAL study, Assessing AlloSure Dd-cfDNA Monitoring Insights of Renal Allografts With Longitudinal Surveillance, monitored 1,092 kidney transplant patients, in a real-world setting, from seven transplant centers for up to three years using the AlloSure Kidney donor-derived cell-free DNA (dd-cfDNA) as part of the standard of care. The study results that AlloSure Kidney can be:

• Used in both subclinical and clinical rejection: Elevated AlloSure dd-cfDNA (>5%) strongly correlated with clinical and subclinical allograft rejection (p<0.001).
• Predictor of de novo donor-specific antibody (dnDSA) formation: Elevated AlloSure dd-cfDNA > 5% associated with a 271% increased risk of dnDSA development (p=0.001).
• Leading indicator of donor-specific antibodies:AlloSure dd-cfDNA was elevated 91 days (median) ahead of DSA identification.
• Superior to serum creatinine: AlloSure showed a 62% relative improvement over serum creatinine in identifying subclinical and clinical rejection (area under the curve [AUC] of 80% vs. 49% respectively).
• Used to identify estimated glomerular filtration rate(eGFR) decline: Persistently elevated AlloSure (>1 result above 0.5%) predicted a > 25% decline in eGFR over 3 years (HR 1.97, p = 0.041), while persistently low levels identify allograft quiescence.

AlloSure is the first dd-cfDNA test to demonstrate clinical utility in prediction of de novo donor-specific antibody, and both subclinical and clinical rejection in a long-term study.

AlloMap^® Kidney CLIA Validated – One Step Closer to Launching Multimodality KidneyCare

CareDx successfully completed Clinical Laboratory Improvement Amendments (CLIA) validation for AlloMap^® Kidney, a blood-based gene expression classifier that identifies immune quiescence, and is an important biomarker needed to comprehensively assess immunological risk of rejection and allograft health. Completing AlloMap Kidney CLIA validation represents the next step for CareDx in offering a more comprehensive, multimodality assessment of kidney transplant health.

In clinical validation, published in Kidney360,² AlloMap Kidney demonstrated the ability to differentiate between rejection (both T-cell mediated rejection [TCMR] and antibody-mediated rejection [AMR]) and immune quiescence, and provide an assessment of immunological activity additive to the allograft injury information derived from AlloSure Kidney donor-derived cell-free DNA (dd-cfDNA), with a combined area under the curve (AUC) of 0.894. Together, these two biomarkers offer a more comprehensive assessment of kidney health compared to the current standard of care.

CareDx’s AlloMap Kidney along with AlloSure Kidney forms KidneyCare, a multimodality solution that has been studied in the Outcomes of KidneyCare in Renal Allografts (OKRA) registry across 50 transplant centers.

Study Initiated Using iBox Artificial Intelligence to Monitor Kidney Transplant Patients

CareDx strategic partner, Cibiltech, a French MedTech company that develops artificial intelligence-based products for predictive medicine, has initiated the CIBIL clinical trial to evaluate the performance of iBox artificial intelligence (AI) as a prognostic measure of organ survival in kidney transplant patients.

The CIBIL “Clinical Impact of the iBox as an Early Intervention tooL” trial is a prospective randomized controlled trial being conducted internationally with 450 patients to evaluate the clinical and health economic benefits of using iBox to predict allograft survival in the follow-up of kidney transplanted patients (NCT05112315). iBox has been previously validated by the Paris Transplant Group in a seminal AI paper for transplantation in the British Medical Journal.³

CareDx is a minority owner of Cibiltech and holds exclusive rights to commercialize iBox in the United States. iBox is an algorithm developed by the Paris Transplant Group, which determines the probability of graft survival three, five, and seven years after evaluation.

The results from Cibiltech’s CIBIL study and CareDx’s OKRA study will demonstrate clinical utility of iBox for transplant patient management. The initiation of the CIBIL study represents a key milestone for CareDx as it evolves its multimodality pipeline with iBox and its prognostic capabilities to assess organ graft survival.

CareDx Introduces XenoSure & XenoMap for Xenotransplantation Research

XenoSure^™ donor-derived cell-free DNA (dd-cfDNA) and XenoMap^™ gene-expression profiling are now available for investigational use in xenotransplantation research and post-xenotransplant clinical monitoring.  These products represent the world’s first surveillance solutions for investigational use in xenotransplantation.

Surgeons from the University of Maryland School of Medicine (UMSOM) recently used XenoSure and XenoMap, two complementary, non-invasive CareDx surveillance solutions, experimentally, for multimodal assessment of organ graft health in the world’s first pig-to-human heart xenotransplant. XenoSure is used to detect graft injury and XenoMap to assess immune quiescence.

In May 2021 CareDx announced a minority investment in Miromatrix, a biotechnology company working to eliminate the need for an organ transplant waiting list through the development of implantable engineered biological organs, to help advance their important work. CareDx and Miromatrix are also collaborating on certain research and development activities using CareDx technology.

Xenotransplantation Innovation Day Held

CareDx brought together leading transplant experts to share latest advancements in the field of xenotransplantation after genetically modified pig kidneys and, separately a pig heart, were recently successfully transplanted, two medical firsts.

The event included an update from Muhammad M. Mohiuddin, MD, Professor of Surgery and Scientific Director of the Program in Cardiac Xenotransplantation at the University of Maryland School of Medicine who co-led the world’s first successful living pig-to-human heart xenotransplant and an update from Robert A. Montgomery, MD, DPhil, Professor and Chair of the Department of Surgery and Director of the Transplant Institute, NYU Langone Health, and surgeon who performed the world’s first successful kidney xenotransplant. Recent developments of clinical-grade, human-compatible organs, and cells were provided by eGenesis and Miromatrix.

Opening remarks were delivered by professional and patient society leaders including:  American Society of Transplant Surgeons (ASTS), A. Osama Gaber, MD, President-Elect; National Kidney Foundation, Paul M. Palevsky, MD, President; The International Society for Heart and Lung Transplantation (ISHLT), Andreas Zuckermann, MD, President-Elect; and Transplant International Organization (TRIO), James Gleason, President and heart transplant recipient.

CareDx’s AlloCare App Helps Pre-Transplant Patients Navigate the Waitlist Process

CareDx’s popular, user-friendly AlloCare^® mobile phone health app, now integrated with TxAccess and features a “virtual roadmap” to help patients track and complete the requirements needed to be considered for placement on a transplant waiting list and aims to help more patients with kidney failure receive an organ transplant.

Since its introduction in September 2020, the AlloCare mobile app has been downloaded more than 25,000 times. AlloCare already helps patients navigate their post-transplant journey by providing tools to track their personal health metrics and test results, manage their complex medication regimens, and connect with other users who have had a transplant. Today, these new enhancements powerfully link participating transplant centers, referring providers, and pre-transplant patients in better navigating the complex pre-transplant process so that more patients eventually receive a transplant.

Partnership with MOTTEP to Support High-Risk Underserved Communities

CareDx joined forces with MOTTEP (Minority Organ and Tissue Transplant and Education Program) to help advance its mission of increasing the number of minority-donated organs and greater adoption of disease prevention behaviors which reduce the incidence of end-stage disease and the need for organ transplantation in high-risk, underserved communities.

MOTTEP’s mission is to reduce the rate and number of ethnic minority Americans needing organ and tissue transplants through disease prevention education and to increase minority organ donations to improve transplant success by finding better matches from similar minority ethnic groups.

CareDx Submits Letter to CMS in Response to Request for Transplant Patient Needs

The Centers for Medicare and Medicaid Services (CMS) requested Public Comments on the “Health and Safety Requirements for Transplant Programs, Organ Procurement Organizations, and End-Stage Renal Disease Facilities.” CareDx responded by conducting a survey with Its patient network, delivering insights from over 250 kidney, heart, lung, and liver transplant patients.

The survey identified four main areas for improvement to better support transplant patients across the continuum of care: 1) there is a need to create greater public awareness about the need for more registered organ donors to ensure a robust transplant ecosystem in the future; 2) more patient education is needed to prevent end-stage disease and improve post-transplant outcomes; 3) transplant patients are looking for ways to get on organ waitlists sooner; 4) patients are seeking greater financial assistance to help them manage chronic illnesses.

CareDx Advocates for Kidney Transplant Patients in Partnership with NKF During National Kidney Month

CareDx teamed up with the National Kidney Foundation (NKF) to support National Kidney Month initiatives aimed at improving outcomes for kidney transplant recipients and those suffering from kidney failure. This marked the seventh consecutive year that CareDx supported NKF’s Kidney Patient Summit on Capitol Hill, which took place virtually on March 2, 2022. Patient representatives were on hand advocating for more research funding to accelerate the early detection of chronic kidney disease, which could help physicians reverse or delay the need for transplantation.

Patient Education Webinars Conducted – Recording Can Be Found Here

• Optimizing For The Long-Term Success Of Transplant Patients
• Ask the Experts: Post-Transplant Nutrition
• Heart Health Across the Kidney Transplant Journey
• COVID-19: Boosters, Antibodies & Continued Risk
• Innovations in Kidney Care
• Transplant Confessions: I Wish I Would Have Known

CEoT Symposium Featured Latest Multimodality Innovations in Kidney & Lung Transplant Surveillance & COVID-19 Abstract

CareDx hosted the symposium, “Improved Precision with a Multimodality Approach,” during the annual American Society of Transplantation Cutting Edge of Transplantation (CEoT) on Thursday, April 7. The latest advancements in multimodality surveillance using CareDx’s AlloSure donor-derived cell-free DNA (dd-cfDNA), AlloMap gene-expression profiling, and other new emerging modalities for assessing allograft injury, rejection, and infection in kidney and lung transplantation were presented.

Additionally, in an accepted abstract, “Kinetics of dd-cfDNA in Kidney Transplant Recipients Following SARS-CoV-2 Vaccination Booster Administration,” NYU Langone Health highlights the use of AlloSure Kidney for monitoring vaccine-related immunological graft injury. The study showed that the stability of dd-cfDNA after SARS-CoV-2 vaccine booster administration reinforces the vaccine’s safety profile in kidney transplant patients.

Professional Education Webinars Conducted – Recording Can Be Found Here

• Optimizing For The Long-Term Success of Transplant Patients
• Managing Your Outcomes in a World of Imperfect Organs and Higher Risk Recipients – Two Parts
• Score 6 Advanced Options and Troubleshooting Tips – Fast Results with Automated Analysis
• AlloSeq HCT – The Latest Innovation in NGS-based Chimerism Testing

CareDx Acquires The Transplant Pharmacy, Expanding Medication Adherence Services

CareDx acquired The Transplant Pharmacy, a transplant focused pharmacy, to expand its medication management and adherence services. The Transplant Pharmacy provides individualized transplant pharmacy services for patients at multiple transplant centers located throughout the United States. Dedicated to patient service and medication adherence, the pharmacy also offers an online patient portal and mobile app for medication ordering and reminders.

The acquisition of The Transplant Pharmacy expands CareDx’s medication adherence-focused healthcare solutions for patients, which currently includes products such as: AlloCare^®, a comprehensive mobile health app for managing the day-to-day health of patients pre- and post-transplant; Transplant Hero^™, a pill reminder app; and MedActionPlan^®, a robust medication management and adherence platform used by more than 100 healthcare systems.

CareDx Wins $44.9M in Damages in False Advertising Trial Against Natera

The jury found that Natera intentionally and recklessly misled the transplant community by deliberately engaging in false advertising in the promotion and marketing of its Prospera kidney transplant rejection assessment test. CareDx was awarded monetary damages totaling $44.9M: $21.2M in compensatory damages and $23.7M in punitive damages.

Overwhelming evidence emerged at trial that demonstrated that Natera made false statements that its senior executives knew were based on unscientific, unreliable, and inappropriate conclusions to market Prospera. The trial underscored the value of AlloSure^®’s clinical excellence as the only donor-derived cell-free DNA (dd-cfDNA) test that has prospective, multicenter validation published. The jury did not find CareDx liable for false advertising under the Delaware Deceptive Trade Practices Act, or intentional and willful false advertising or unfair competition. Notably, the jury rejected all of Natera’s challenges to AlloSure performance claims.

The jury found Natera liable for false advertising based on Natera’s false comparisons of its kidney transplant assessment test, Prospera, to CareDx’s market leading AlloSure technology. Specifically, the jury found Natera liable for: 1) false advertising under the Lanham Act; 2) false advertising under the Delaware Deceptive Trade Practices Act; 3) Intentional and willful engagement in false advertising; and 4) Intentional or reckless engagement in unfair competition.

CareDx Partners with the ESOT to Support the Use of AlloSeq cfDNA in Europe

CareDx is partnering with the European Society for Organ Transplantation (ESOT) to provide education for its membership on the clinical evidence supporting the use of donor-derived cell-free DNA (dd-cfDNA) to monitor transplanted organ health.

CareDx’s partnership with the European Society for Organ Transplantation represents a key step forward in educating the European transplant community about the clinical utility of AlloSeq cfDNA, its kit version to allow donor-derived cell-free DNA assessment. Over time this may help expand access to this leading technology, and make it the standard of care for organ transplant patients globally.

References:

1. Bu L, Gupta G, Pai A, et al, Validation and clinical outcome in assessing donor-derived cell freeDNA monitoring insights of kidney allografts with longitudinal surveillance (ADMIRAL) study, Kidney International (2022), doi: https://doi.org/10.1016/j.kint.2021.11.034.
2. Akalin E, Weir MR, Bunnapradist S, et al. Clinical Validation of an Immune Quiescence Gene Expression Signature in Kidney Transplantation. Kidney360. December 2021, 2 (12) 1998-2009; DOI: https://doi.org/10.34067/KID.0005062021
3. Loupy A, Aubert O, Orandi BJ, Naesens M, Bouatou Y, Raynaud M, et al. Prediction system for risk of allograft loss in patients receiving kidney transplants: international derivation and validation study. BMJ 2019; 366: l4923. doi: https://doi.org/10.1136/bmj.l4923