Caredx sep 2017 170831 by Olerup SSP AB

ISSUE 4, Sep 2017

AlloSure qualified for Medicare coverage and reimbursement ®

HLA typing within an hour ”An Olerup QTYPE® 11 run on a validated real time PCR instrument takes approximately 45 minutes and, when adding time to prepare the plate and the results analysis, we have a full 11 loci typing in around an hour”, says Ben Passey, Development Manager at Olerup.

■ Page 6 –7 Introducing AlloSure, a clinical grade, NGS-based test that measures circulating donor-derived cell-free DNA (dd-cfDNA) resulting from kidney allograft injury. CareDx announced on August 24, 2017 that AlloSure qualified for Medicare coverage and reimbursement for dd-cfDNA in Blood kidney transplant patients effective October 9th, 2017.

■ Page 4 – 5 Active Rejection Kidney transplant

In January 2017 Olerup/CareDx announced the acquisition of Conexio´s HLA SequenceBased Typing (SBT; Sanger method) business from Illumina.

■ Page 8

No Active Rejection

Advancing the pre- to post-transplant continuum The pre- to post-transplant continuum represents the patient care pathway for organ transplantation that spans the time between consideration of a transplant, the life of the patient with or without a functioning allograft, and encompasses the steps and decision points in navigating disease and health management based on medical guidelines, recent evidence, expert consensus and more recently informed by precision diagnostics.

■ Page 2

SBT Resolver™ becomes Olerup SBT™

Continuously improving our products The seemingly endless description of new HLA alleles presents a significant challenge to both our users in the lab and to our R&D colleagues at Olerup SSP AB in Stockholm, Sweden. That said, we are not content to sit idle and let the performance of our widely-used products decline.

■ Page 10

CareDx news SEP 2017

Advancing the pre- to post-transplant continuum With great pleasure, we bring you the latest installment of CareDx news. More than 15 months have passed since CareDx, Inc. acquired Olerup’s parent company Allenex AB. This synergistic combination has resulted in a dedicated transplant company committed to innovation along the preto-post transplant continuum. Said another way, the pre-to post transplant continuum represents the patient care pathway for organ transplantation that spans the time between consideration of a transplant, the life of the patient with or without a functioning allograft, and encompasses the steps and decision points in navigating disease and health management based on medical guidelines, recent evidence, expert consensus and more recently informed by precision diagnostics. We continue to be customer and patient focused with short and long term clinical outcomes held as the highest priorities. Our core products, Olerup SSP® for HLA matching and AlloMap for heart rejection monitoring continue to serve foundational roles in addressing the needs of the transplant community.

The year has been an exciting one. Early in the year, we acquired the Conexio Genomics SBT product line from Illumina, ensuring an uninterrupted supply of HLA sequencing kits and continued support of class leading analysis software for our customers. We have witnessed the successful launch of Olerup QTYPE, our rapid qPCRbased HLA typing assay on the Roche LightCycler 480 II platform, moving swiftly from demos to validation and commercial sales at a number of prestigious laboratories. We are looking forward to a continued wave of demos as our R&D team diligently works to provide timely requested resolution updating, improved software solutions and add new instrument platforms. Finally, we are launching AlloSure, a clinical grade, NGS-based test that measures circulating donor-derived cell-free DNA (dd-cfDNA) resulting from kidney allograft injury. CareDx announced on August 24, 2017 that AlloSure qualified for Medicare coverage and reimbursement for kidney transplant patients effective October 9th, 2017. We believe that better monitoring leads to better outcomes and our commitment to

Gordon Hill Vice President and General Manager, Olerup Inc.

non-invasive transplant surveillance is unwavering. Please join us for our lunch symposium “Advancing the Pre-to-Post Transplant Continuum” to hear more about our ongoing work.

Advancing the Pre-to-Post Transplant Continuum: Date: Tuesday, September 12 Time: 12:00 pm – 2:00 pm Location: Plaza Room Hilton San Francisco Union Square Olerup QTYPE: Advancements in Rapid HLA Typing

Non-Invasive Rejection Monitoring for Thoracic Transplantation

Bruno Vanherberghen, Ph.D. Technical Brand Manager CareDx, Inc. (Olerup SSP, AB)

Kiran K. Khush, MD, MAS Associate Professor of Medicine Stanford University

Clinical Utility of AlloSure, a DonorDerived Cell-Free DNA Test Validated in Kidney Transplantation Robert N. Woodward, Ph.D. Senior Director, R&D CareDx, Inc.

CareDx venues 2017

Please stop by booth 100 to learn more.

CareDx products and representatives can be seen throughout 2017 at the following meetings, conferences and exhibitions. We look forward meeting you.

MEET US AT EVENT

DATE

LOCATION

ASHI National Meeting

September 11 – 15

San Francisco, CA

Eurotransplant Jubilee Meeting

October 4 – 6

Leiden, Netherlands

ASN Kidney Week

October 31 – November 5

New Orleans, LA

Journée éducative

November 22 – 23

Paris, France

MEDICA

November 13 – 16

Düsseldorf, Germany

CareDx news SEP 2017

Speed and Precision in Real Time • Low to intermediate resolution HLA typing of 11 loci in real time • From setup to final results within an hour • TaqMan® technology provides flexibility and multiplexing power to easily add reaction mixes to enhance resolution • Seamless analysis in new SCORE™ 6 software with all test data stored in a central database for easy access and retrieval For Research Use Only

Manufactured by:

CareDx news SEP 2017

AlloSure: A clear path forward NON-INVASIVE

The latest innovation in kidney transplant surveillance can drive better outcomes for your patients CareDx continues to expand its testing services for post-transplant patients with AlloSure. AlloSure is the first and only non-invasive test that assesses organ health by directly measuring allograft injury. AlloSure can accurately determine active rejection, enabling better management of your kidney transplant patients.

LESS

Serum Creatinine DSA

ACCURATE

In diagnosis of Active Rejection

Biopsy

INVASIVE

AlloSure: Better Monitoring. Better Outcomes. Cell-free DNA as a biomarker

Cell-free DNA (cf-DNA) is fragmented DNA in the bloodstream that originates from cells undergoing cell injury and death. When graft injury occurs, donor -derived cell-free DNA (dd-cfDNA) increases in the bloodstream. AlloSure measures dd-cfDNA and is a powerful, non-invasive tool for kidney transplant surveillance. At product launch, AlloSure will be covered by Medicare.

dd-cfDNA in Blood

Active Rejection Kidney transplant

No Active Rejection

For more information, visit www.allosure.com

CareDx news SEP 2017

What is AlloSure? • A sensitive, accurate, and precise measure of organ health • A non-invasive blood test that does not require prior genotyping of the donor or recipient • A rejection rule-out test that has high specificity

Process

When to use AlloSure

• Samples collected in Streck Cell-Free DNA BCT® tubes with no additional processing or preparation required before shipping

• AlloSure Routine Testing Schedule: – Year 1 schedule for AlloSure: Months 1, 2, 3, 4, 6, 9, and 12 – Year 2+ schedule for AlloSure: Quarterly

• Samples are run in-house at CareDx’s CLIA-certified and CAP-accredited clinical laboratory

– The AlloSure Routine Testing Schedule is based on the DART study protocol

• Results reported within 72 hours of blood draw

• Clinically Indicated For Cause: – Use AlloSure as a step before the decision to perform a clinically indicated biopsy – Examples of Clinical Indications: High Creatinine, Proteinuria, DSA, BKV, DGF • Rejection Therapy Monitoring: – A monthly AlloSure for the first 3 months post-rejection treatment

CareDx news SEP 2017

Olerup QTYPE: Advancements in Rapid HLA Typing The Olerup QTYPE system enables speed and precision in HLA typing at a low to intermediate resolution for samples requiring a fast turnaround time. The research use only product was launched last year at ASHI and consists of the Olerup QTYPE HLA typing kit and the SCORE 6 interpretation software on the Roche LightCycler 480 II qPCR instrument.

of instruments and we have had to take into consideration things like PCR cycling blocks, cycling parameters, instrument optics, and instrument sensitivity to name just a few. For the kit aspect itself, we have considered the actual plastics, as the ABI platform is usually run with transparent plates, as well as the values used to define a positive and negative reaction.

In the year since the Olerup QTYPE launch, we have performed product demonstrations in 13 different countries. Several labs are now regular users and additional labs are proceeding through their validation phase. Several thousand tests of the Olerup QTYPE test have now been performed in clinical routine, not a bad start for our TaqMan-based approach for rapid and precise HLA typing!

We have made continual steady progress and generated extensive internal data on all the various components of the kit. In collaboration with external centers, over 300 clinical samples have been analyzed on the QS6, QS7 and ViiA-7 combined. The SCORE 6 software has been upgraded to allow import of ABI data and to enable analysis. We are currently fine-tuning the kit and the software to finalize the transition of the Olerup QTYPE product onto the ABI instruments.

Platform development In the current Olerup QTYPE lot, over 800 potential reactions (including the internal control) are present across 3 different colors over 40 cycles, highlighting the level of complexity. Over the last year, work has been ongoing to allow the Olerup QTYPE test to be run on the ABI QS6, QS7 and ViiA-7. This is a completely different set

Simple workflow The kit includes all necessary components for PCR, including a hot-start master mix. Only water and DNA need to be added to the master mix prior to dispensing across the plate. The assay is sensitive and requires only 5 μg of DNA, including overfill, for a full low to intermediate resolution 11 locus

typing. Once the plate has been prepared, seal it with the included optically-clear sealing sheet, briefly centrifuge and place it in the real time cycler. Data is collected in real time. After the run finishes, the raw data can be imported into SCORE 6, our purpose-built software for real time data analysis. Our well-known software has been simplified for increased user-friendliness and the underlying database technology upgraded for improved reliability. In the software, an Olerup QTYPE run is associated with sample-specific information to obtain the final typing result.

HLA typing within an hour ”An Olerup QTYPE 11 run on a validated real time PCR instrument takes approximately 45 minutes and, when adding time to prepare the plate and the results analysis, we have a full 11 loci typing in around an hour”, says Ben Passey, Development Manager at Olerup.

Precision in real time, multiplexing for best possible resolution The Olerup QTYPE HLA typing kits use TaqMan probe technology, a powerful

A complete workflow offering speed and precision in real time Olerup QTYPE HLA typing kit

10 min

45 min

• Prepare DNA/Master Mix

• Set up instrument

– Mastermix including Taq polymerase

• Dispense plate

• Insert plate

– Optically clear adhesive sealing sheet

• Seal plate

• Run

– Lot-specific kit information

• Centrifuge

KIT CONTENTS – 384 well plate containing pre-aliquoted, dried primers and hydrolysis probes

CareDx news SEP 2017

and flexible multiplexing tool. This will allow us to have a kit with minimal ambiguities, enhanced resolution and gives us the flexibility to grow with the HLA database. TaqMan probes also eliminate primer dimers and PCR artefacts with no waiting for endpoint melt curves. Briefly, TaqMan probes are sequencespecific primers with a fluorescent reporter molecule on one end and a fluorescence quencher molecule on the other end. Due to their close proximity on the probe, all the fluorescence emitted by the reporter is absorbed by the quencher molecule, resulting in no net signal. They are designed to bind between the two PCR primer and during the extension step, the PCR polymerase cleaves the TaqMan probe, freeing the fluorescent probe into the supernatant. With each cycle, the real time instrument automatically monitors the accumulation of fluorescence over time. These parameters are then used to automatically detect a positive or negative amplification. Overall, each reaction is composed of at least two Olerup SSP primers and a sequencespecific TaqMan probe. Hence, each reaction uses three layers to determine

specificity. Clearly, this increases the resolution power of each individual mix.

Continuous product improvements A full plate consists of 384 wells, with a single well to detect potential DNA contamination. With 383 wells dedicated towards HLA-specific reactions, and four colors, we have a total of 1,532 potential reactions. A single channel is dedicated to the internal amplification control, three channels can be used for HLA-specific reactions. This gives a potential of 1,149 HLA-specific reactions in a 384 well plate. In its current format, Olerup QTYPE 11 has 429 HLA-specific reactions, using approximately 37% of its total potential. Ben Passey, Development Manager, Olerup SSP AB

Similar to our trusted and proven approach to the Olerup SSP product line, we will continuously develop and improve the Olerup QTYPE product based on market needs.

Trusted and reliable support With more than 25 years’ experience in HLA, Olerup is your trusted partner in transplantation. We pioneered the way with our innovative Olerup SSP product line in the 90’s. We have continuously

maintained a high-standard for this product line and are known for having the kits with the best resolution on the market. This is a promise we will continue to deliver on with our real-time product Olerup QTYPE, delivering speed and precision.

MULTIPLEXING POTENTIAL – 384 wells and 4 colours allowing 1,536 individually detected reactions – One color reserved for internal amplification control leaving 1,149 reactions available for HLA-specific reactions

5 min • Transfer data • Automatic data analysis • Review results

– Capacity to continue to develop and upgrade the kits with new database releases

CareDx news SEP 2017

SBT Resolver becomes Olerup SBT In January 2017 Olerup/CareDx announced the acquisition of Conexio´s HLA SequenceBased Typing (SBT; Sanger method) business from Illumina. The acquisition comprised the complete SBT product line, including HLA locus-specific assays, HARPS to resolve heterozygous SBT ambiguities, and the Olerup Assign TM SBT software for HLA sequence analysis.

typing solutions; HLA Olerup SSP typing with Olerup SSP kits and HLA typing in real-time with Olerup QTYPE. A new subsidiary, CareDx Pty Ltd, has been established in Fremantle, Australia, where we will continue to manufacture Olerup SBT products. We are pleased to have included both former Conexio colleagues as well as new employees at CareDx Pty Ltd, Fremantle. Building on an already extensive and proven product line, continuous work with software and assay development will soon make available both new and improved Olerup SBT products.

With the acquisition we are moving from being a distributor to also take complete ownership of manufacturing and future development of SBT products. Visually, the SBT Resolver product line will change name from SBT Resolver to Olerup SBT. Customers will start to receive the new branded Olerup SBT products in late 2017/ beginning 2018. We are excited to continue providing customers with high-resolution HLA sequencing and believe Olerup SBT is greatly complementing our other HLA

Distribution and support of the HLA sequence-based typing products will continue to be managed by the Olerup organization, ensuring on time delivery and expert help from our technical support team when needed.

Håkan Hall, General Manager SBT, Olerup SSP AB

Products for

HLA Sequencing Based Typing LOCUS

EXON 1

EXON 2

EXON 3

EXON 4



• Comprehensive set of HLA Class I and II HARPS • Compatible with OLERUP Assign SBT v4.7 and v471 • DRB3, DRB4, DRB5 and B57 typing kits

EXON 5

EXON 6

EXON 7



CareDx news SEP 2017

BigDye and ExoSAP-IT ®

- Now distributed by Olerup Starting November, 2016, through collaboration with Thermo Fisher Scientific, Olerup will be distributing BigDye Terminator v1.1/v3.1 Cycle Sequencing Kits and ExoSAP-IT for PCR Product Cleanup to the HLA community. Being committed to providing our HLA customers the best level of service we are pleased to announce the addition of these two new accessory products to product portfolio. Including BigDye and ExoSAP-IT reagents to our product portfolio will provide Olerup SBT users a more complete SBT solution.

• BigDye Terminator Cycle Sequencing Kit v3.1 and v1.1* • ExoSAP-IT for PCR Product Cleanup

PRODUCT NAME

SIZE/QTY.

PRODUCT NUMBER

BigDye Terminator v1.1 Cycle Sequencing Kit

100 reactions [800ul]

4337450C

BigDye Terminator v3.1 Cycle Sequencing Kit

100 reactions [800ul]

4337455C

ExoSAP-IT for PCR Product Cleanup

100 reactions [200ul]

78200

* License grant: BigDye is available for purchase in combination with Olerup SBT products

Distributed by:

For more information please contact your local Olerup distributor, www.olerup.com/contact-us/

www.olerup.com

CareDx news SEP 2017

Olerup takes great pride in providing the most up-to-date Olerup SSP kits in the market The seemingly endless description of new HLA alleles presents a significant challenge to both our users in the lab and to our R&D colleagues at Olerup SSP in Stockholm, Sweden. That said, we are not content to sit idle and let the performance of our widely-used products decline. We strive to

meet lab expectations by working in close collaboration and push ourselves to update Olerup SSP kits with every new lot. The table below reflects our recent work in this area. New Olerup SSP lots that have been produced in the first 6 months of 2017 now include 1650+ unique primer mixes. Of

these, 28% were new formulations, either through multiplexing (24%) or through adding new wells to the kits (4%). Weâ&#x20AC;&#x2122;ll be bold here: if you currently use SSP in your lab you may want to consider going with Olerup, the only company fully committed to SSP for more than 25 years.

Olerup SSP allele updating work in numbers across the product line Total number of produced and unique primer mixes (wells)

1652

Out of which: Multiplexing instances for resolution of new alleles Added wells Sum of changes on primer mix level for allele updating

Olerup QTYPE development and delivery is no exception to the rule above Considering our commitment to having the most up-to-date Olerup SSP kits in the market, it should be no surprise that Olerup chose a TaqMan approach for its rapid qPCR HLA typing assay. Utilizing just a mere one third of the capacity of this proven approach, we achieve allele

resolution results equal to or better than our competitors on a single 384-well plate. The future of qPCR for HLA typing is not only rapid typing, but its flexibility to expand to address new alleles while still maintaining a single plate footprint for convenience. Olerup has a long-term approach assuring sufficient capacity to meet your resolution needs. As a newly launched product, we are

407

24,6%

3,8%

470

28,5%

diligently improving our kits to meet your expectations for both CWD and single antigen resolution while maintaining robustness. As a simple highlight, the table below shows our commitment to rapid development and enhancement of our Olerup QTYPE kits in just the first few lots.

Summary of QTYPE Improvements: Olerup QTYPE11 lot update

Added mixes

Increase since first lot

Additional Resolution

7.27%

Resolve Ambiguity

4.16%

Improved Robustness

5.45%

Total

16.88%

CareDx news SEP 2017

COMING SOON

A clear path forward THE LATEST INNOVATION IN KIDNEY TRANSPLANT SURVEILLANCE CAN DRIVE BETTER OUTCOMES FOR YOUR PATIENTS AlloSure is the first and only clinically and analytically validated, non-invasive test which assesses kidney health by directly measuring allograft injury

Put your patients on a clear path forward with AlloSure FEATURES + Measures donor-derived cfDNA, a direct indicator of kidney injury + Clinically and analytically validated + More accurate than serum creatinine in diagnosis of active rejection + Does not require donor or recipient genotyping + Appropriate for a wide array of patients who are 2 weeks or more post transplant and 18+ years of age + Covered by Medicare

No Active Rejection, n=80 samples from 75 patients Active Rejection = Acute/active ABMR; Chronic, active ABMR; and TCMR IA and greater, n=27 samples from 27 patients.

§ †

For more information: 1-888-255-6627 | www.allosure.com | customercare@caredx.com

Revision 1 Effective 2017-08 LK-10409

GERMANY/AUSTRIA/BENELUX

Olerup Inc

Olerup GmbH

Orders: orders-us@caredx.com General inquiries: olerup-us@caredx.com

Orders: orders-at@caredx.com General inquiries: olerup-at@caredx.com

Technical support: techsupport-us@caredx.com

Technical support

Tel: +1-877-OLERUP1 Fax: +1-610-344-7989

Tel: +43-1-710 15 00 00 Fax: +43-1-710 15 00 10

901 S. Bolmar St., Suite R West Chester, PA 19382

Loewengasse 47/6 1030 Vienna, Austria

NORDIC AND THE BALTICS

AUSTRALIA

Olerup SSP AB

CareDx Pty Ltd

To place your order please use the Nordic Webshop, alternatively contact us via below addresses:

Orders: orders-aus@caredx.com General inquiries: olerup-aus@caredx.com

Orders: orders-se@caredx.com General inquiries: olerup-se@caredx.com

Technical support

Technical support Tel: +46-8-50893900 Fax: +46-8-7178818

Tel: +61 8 9336 4212 20 Collie Street, Fremantle, WA 6160, AUSTRALIA

Franzéngatan 5 112 51 Stockholm, Sweden

OTHER REGIONS

Carnew 20170831-3

Olerup product lines are in other regions made available through our network of specialized distributors.