CareDx News May 2018 by Olerup SSP AB

ISSUE 4, May 2018

Olerup QTYPE receives CE mark ®

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CareDx at 2018 year´s EFI meeting At the annual EFI meeting in Venice, Italy CareDx will be exhibiting at the ground floor in Palazzo del Casino. If you are attending please visit our Booth to learn more about what´s new from our company. We are hosting Olerup QTYPE workshops, demonstrating SCORE 6 and inviting you to share a cup of coffee with us. Please also join our Lunch Symposium on Thursday, May 11 where exciting news will be shared with the audience

Cell-free DNA as a Biomarker in Transplantation Cell-free DNA (cf-DNA) is fragmented DNA in the bloodstream that originates from cells undergoing cell injury and death.Read more on how CareDx is providing a solution for kidney transplant recipients on

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CareDx signs reseller agreement with Thermo Fisher CareDx has recently signed an agreement with Thermo Fisher allowing CareDx and its distributors to resell the QuantStudio™ instruments in combination with Olerup QTYPE. Read more on

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Providing the most fit-for-purpose products In parallel to updating our well known Olerup SSP product line our R&D department continues to work with its long-term approach assuring sufficient capacity to meet your resolution needs. Read more on

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CareDx news MAY 2018

News from Vienna More than 24 months have passed since CareDx, Inc., based in Brisbane, California, acquired Olerup’s parent company Allenex AB. Both companies have well established core products in transplantation and the combination of both sets of expertise creates a focused diagnostics company fully covering the pre- to post-transplantation continuum. Please read more about the offering from us to the transplant community in this issue of CareDx news.

Olerup QTYPE Really exciting news for us is the CE marking of the Olerup QTYPE, our rapid real time based HLA typing assay. The CE mark is a certification mark provided by our Notified Body indicates conformity to the In Vitro Diagnostics Directive and applicable standards. It is essential for a Europe-wide launch product and almost a prerequisite for Olerup QTYPE 11 availability in Europe. Throughout the last year we have been successful with running many workshops around Europe of Olerup QTYPE on the Roche LightCycler® 480 II platform. This

was done through our own sales organization in Europe and in USA but also through our well-established distributor network in Europe. Inspired by the positive feedback we have received from these Olerup QTYPE 11 workshops we are not only continuing with them, but expanding the number we have planned. Recent work has been focusing on making Olerup QTYPE available also on the Applied Biosystems QuantStudio™ 6, QuantStudio 7 and ViiA™7. We also continue to add resolution to the product and improve our software solution (SCORE 6).

success through Improvements in Diagnostics” to hear more about these exciting developments and more exciting news from CareDx.

CareDx reseller of QuantStudio instruments An important agreement was reached with Thermo Fisher. CareDx now has a reseller agreement with Thermo Fisher for the QuantStudio suite. This will allow us to approach laboratories in Europe and US not only with reagents but also with instruments for real time PCR typing in HLA. Do you want to find out more? If you are attending EFI, please join us for our lunch symposium “Olerup – Ensuring Transplant

Roswitha Keller General Manager, Olerup GmbH

CareDx venues 2018 CareDx products and representatives can be seen throughout 2018 at the following meetings, conferences and exhibitions. We look forward meeting you.

MEET US AT EVENT

DATE

LOCATION

EFI National Meeting

May 9 – 12

Lido, Venice

IDRC Meeting

June 28 – 30

Munich, Germany

ASHI Regional Workshop

June 28 – 30

Cleveland, OH

BISHI Meeting

September 5 – 6

Cardiff, UK

ASHI National Meeting

October 1 – 5

Baltimore, MD

Eurotransplant Meeting

October 4 – 6

Leiden, Netherlands

CareDx news MAY 2018

Now

CE / I V D

Speed and Precision in Real Time With Olerup QTYPE time is on your side •

An HLA typing within 60 minutes

•

TaqMan probes

•

Multiplexed - up to 1,536 individual reactions

•

Continuous resolution improvements

•

All alleles covered at least twice in different reactions

Manufactured by Olerup SSP AB www.olerup.com

NOW ALSO available on QuantStudio™ 6, 7 and ViiA™ 7

Distributed by Olerup www.olerup.com

QTY-180417-10

Roche LightCycler 480II

CareDx news MAY 2018

Available now and fully covered by Medicare 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 MAY 2018

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 MAY 2018

Olerup QTYPE: CE marked and an expanded instrument base

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.

The Olerup QTYPE system enables speed and precision in HLA typing. The assay has a total turnaround time from start to finish of 60 minutes and provides a low to intermediate resolution for samples requiring a fast turnaround time. With Olerup QTYPE, time is on your side! We are proud to inform our European market that the Olerup QTYPE product has now been CE marked. In addition, we are pleased to announce that the Olerup QTYPE instrument base has been expanded. When the product was launched at ASHI in 2016, it was available on the Roche LightCycler 480 II real time PCR instrument. Olerup QTYPE can now also be run on the Applied Biosystems QuantStudio 6, QuantStudio 7 and ViiA 7. If you have one of these instruments and are interested in evaluating the performance of the Olerup QTYPE product, come visit us at the booth or talk to your local Olerup distributor!

Simple workflow The kit includes all necessary components for PCR, including a hot-start master mix. Water, DNA and master mix need to be combined prior to dispensing this mixture across the plate. The dispensing can be performed manually or with automation. The assay is sensitive and requires only 5 μg of DNA, including overfill, for a full 11 locus

After the run finishes, the raw data can be imported into SCORE 6, our purpose-built software for real time data analysis. The 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. In addition, we realize that freezer space is valuable in the laboratories. To support our users, we recently reduced the box size of the Olerup QTYPE kit so that it takes up 50% less space.

In the year and a half since the Olerup QTYPE launch, we have performed over 60 product demonstrations in 13 different countries. A continuously increasing number of laboratories are now regular users with additional labs proceeding through their validation phase. Several thousand tests of the Olerup QTYPE test have now been performed. Not a bad start for our TaqMan-based approach for rapid and precise HLA typing!

Now available on: Applied Biosystems QuantStudio™ 6/7 and ViiA™ 7 Roche LightCycler® 480 II

CareDx news MAY 2018

Platform development In the last year, work has been focused on two fronts: CE marking of the product and enabling use of Olerup QTYPE on the Applied Biosystems instruments QS6, QS7 and ViiA 7. In the early parts of this year, together with 3 centers, Olerup QTYPE was validated in a performance evaluation study, including 111 clinical samples. Based on this and a range of other studies demonstrating among other aspects, the stability, reproducibility, repeatability and accuracy of the product, the product was CE marked. If visiting EFI, please join our lunch symposium on Thursday at 12 o’clock for more information! In collaboration with 17 clinical laboratories more than 300 clinical samples were analysed on 27 instruments including the Roche LightCycler 480 II, Applied Biosystems QS6, QS7 and ViiA 7. The SCORE 6 software has been upgraded to allow import of ABI data and to enable analysis. In addition to this, we have added additional features in the product to improve and increase robustness and accuracy.

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 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 sequence-specific 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.

Continuous product improvements A full plate consists of 384 wells which can be detected in four different fluorescent channels giving us a total possibility of 1,532 potential reactions. 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. The plate is not even half full meaning that we will continue to improve resolution by adding reactions based on requirements.

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.

These parameters are then used to automatically detect a positive or negative amplification. Overall, each reaction is composed of at least two SSP primers and a sequence-specific TaqMan probe. Hence, each reaction uses three layers to determine specificity. Clearly, this increases the resolution power of each individual mix. Ben Passey, Development Manager, Olerup SSP AB

Speed: HLA typing in one hour

10 min

45 min

5 min

START

RUN

FINISH

Prepare plate

Run on instrument

Analyse results

CareDx news MAY 2018

Olerup SBT update our other HLA typing product lines; Olerup SSP, and Olerup QTYPE. Furthermore, users may have noticed the significantly reduced sizes of our kit boxes, saving space both on our and the customer end. During the last year we have spent much effort in improving the Assign software, and in 2018 we are proud to have launched a new release of Assign v471, Olerup re-branded, but more importantly, updated the software to work also on a 64-bit operating environment. The 64-bit version of Olerup Assign SBT™ v471 provides faster data import and a faster HLA analysis experience.

CareDx HLA sequence-based typing products are developed and manufactured by CareDx Pty Ltd, our wholly owned subsidiary based in Fremantle, Australia. Our Fremantle team (see picture) can look back at a year of successful integration activities where the SBT business, acquired from Illumina in 2017, now is fully integrated in our organization. From a user view the most noticeable change has probably been the re-branding of the SBT product line, to Olerup SBT™, now similar to the branding of

cing products continue to be managed by the Olerup organization, ensuring on time delivery and expert help from our technical support when needed.

For the future we are committed to upgrade our sequencing product portfolio to meet new user needs and requirements. Work is on-going to provide assays enabling whole HLA gene sequencing, delivering HLA genotyping at the highest resolution. Distribution and support of HLA sequen-

CareDx team, Fremantle Australia

Håkan Hall, General Manager SBT, Olerup SSP AB

Products for

HLA Sequencing Based Typing LOCUS

EXON 1

EXON 2

EXON 3

EXON 4



• C omprehensive set of HLA Class I and II HARPS • C ompatible with OLERUP Assign SBT v471 • D RB3, DRB4, DRB5 and B57 typing kits

EXON 5

EXON 6

EXON 7



CareDx news MAY 2018

BigDye and ExoSAP-IT ®

- Distributed by Olerup Through collaboration with Thermo Fisher Scientific, Olerup is distributing BigDye Terminator v1.1/v3.1 Cycle Sequencing Kits, ExoSAP-IT and ExoSAP-IT Express for PCR Product Cleanup to the HLA community. Being committed to providing our HLA customers the best level of service we are pleased to be a provider of these accessory SBT products. Including BigDye and ExoSAP-IT reagents to our product portfolio provides Olerup SBT users a more complete SBT solution.

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

ExoSAP-IT Express for PCR Product Cleanup

100 reactions [200ul]

75001

* 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 MAY 2018

CareDx is committed to providing the most fit-for-purpose products for HLA typing by real time- and conventional PCR with Olerup QTYPE and the Olerup SSP product line CareDx has, through the Olerup product lines, a long-term approach assuring sufficient capacity to meet your resolution needs. Considering our commitment to have the most up-to-date Olerup SSP kits in the market, it should be no surprise that CareDx chose a TaqMan approach for its rapid real time PCR HLA typing assay, Ole-

rup QTYPE. The future of real time PCR 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 QTYPE 11 is as of April 2018 CE marked. Furthermore, we are diligently

improving our Olerup QTYPE kits to meet your expectations for both CWD and single antigen resolution. The table below shows data on the Olerup QTYPE performance characteristics leading up to CE certification.

Summary of Olerup QTYPE Performance Characteristics: Olerup QTYPE 11

Study Specifics

Results

Accuracy

Agreement for 150 well-characterised IHWG cell line samples

100% overall agreement across 11 loci achieved

Reproducibility and Repeatability

Concordance across 11 loci between different sites, operators and time periods.

100% concordance across 11 loci achieved in all R&R studies

Concordance across replicates on a single instrument Lot-to-lot concordance between 3 different lots of QTYPE11

Method Comparison

Performance validation of Olerup QTYPE 11 in 3 centers, using 111 blinded clinical samples.

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 in Stockholm, Sweden. The tables

below reflects our recent work in this area for the Olerup SSP product line. To serve this well-positioned product line, during the last 15 months we produced 3893 unique

Overall percent agreement with the reference methods greater than 99.1% (with lower 95% confidence interval of 0.958-0.977) achieved

primer mixes of which 25,7 % stemmed from our continuous work with kit resolution, with a focus on alleles that have a confirmed status in the IMGT/HLA database.

Olerup SSP allele update work in numbers across the product line for the year of 2017 through March 2018 Total number of produced and unique primer mixes (wells)

3893

Out of which: Multiplexing instances for resolution of new alleles

883

22,7%

Added wells

118

3,0%

1001

25,7%

Sum of changes on primer mix level for allele updating

CareDx news MAY 2018

CareDx, now reseller of ABI QuantStudio instruments CareDx recently signed a non-exclusive agreement enabling us and our distributors to resell the QuantStudio suite of instruments in conjunction with Olerup QTYPE. This allows us to offer our customers a convenient way of switching to Real Time. To be able to provide both reagents and instruments needed by the laboratory to run Olerup QTYPE is of high value. With the Applied Biosystems real-time PCR platforms, you get excellent performan-

ce, reliability, and support. Designed for compatibility with TaqMan Assays and the flexibility of unlimited real-time chemistry choices, makes it easy for you to get started with your reagents.

CareDx pre-transplant products sold in more than 70 countries Our team consists of the Olerup sales teams and our well-established distributor network. We provide our products globally

QuantStudio 6 Flex System

and currently sell our products in more than 70 countries. Many of our distributors have worked with us for more than ten years and are well known in tissue typing laboratories in their respective region. To learn more about how the CareDx team can assist you in evaluating the QuantStudio instruments please contact your local CareDx contact.

QuantStudio 7 Flex System

Colors

5 colors

6 colors (21 filter combinations)

Available Formats

96-well

96-well Fast

384-well

384-well card (384-well microfluidic card)

Dimensions

90.7 ⨯ 74.7 ⨯ 12.5 cm

Block change Touch screen

90.7 ⨯ 74.7 ⨯ 12.5 cm

Block change from front in less than 1 minute; no tools required Yes • • • • • •

Yes Gene expression miRNA profiling SNP genotyping Copy number variation Protein thermal shift Pathogen detection

• • • • • • • •

Gene expression miRNA profiling SNP genotyping Copy number variation Protein thermal shift High resolution melt Pathogen detection Pharmacogenomics

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

OLE-180504-11

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