Olerup news tabloid sf 141021

NEWS October 2014

Gamma-Type

™

Matching becomes more than HLA Class I and II At the recently held EFI Meeting, data was presented on Gamma-Type™ suggesting that the test can be of great value for matching donor/recipient pairs in HSCT. Read more in the article on page 3.

Olerup Network provides Global Coverage With direct sales in 14 countries and a distributor network covering Europe, Canada, Latin- and South America, Asia, Oceania and parts of Africa, Olerup is truly a Global Provider of transplant diagnostics. During 2013 Olerup added 15 new partners and the growth is expected to continue.

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Introducing Olerup News Anders Karlsson, CEO of Allenex, shares his view with the readers.

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Complement activation and AECA Several studies have shown that both HLA and non-HLA antibodies play an important role in graft rejection.

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Olerup SSP – Teaching an old dog new tricks What’s Now, What’s New, What’s Next?

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Conexio Genomics NGS solution; A unique approach By incorporating traditional HLA loci, as well as non-HLA markers, Conexio will launch a proprietary suite of NGS products.

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Introducing Olerup News The objective of Olerup News is to share with you what we as an organization can offer our customers within the transplantation community. We have a long and successful history with our SSP products for HLA-typing, with which we have been on the front line of HLA for more than 20 years. But, Olerup is more than that today. Olerup is a company with a global reach that offers innovative products to our customers. From our headquarters in Stockholm, Sweden we channel our products via our sales organizations in West Chester, PA, USA and in Vienna, Austria to countries all over the world. We have our own sales organization in the United States, Germany, Austria, Belgium, The Netherlands and within the Nordic countries, but are also partnering with a very well-established network of local distributors in other countries across the globe.

The reach of the Olerup sales channels are continuously increasing, and every year we add several new sales partners into our network. The common requirement for Olerup’s sales partners is a strong focus on HLA typing and transplantation diagnostics.

They are all selected to work with our products because they have a strong presence in this market.

Introducing Several New Products Today, we are not only providing SSP kits for HLA typing, but a broader range of products to be used within the labs servicing the transplantation community. Olerup is very happy to also provide products for HLASBT typing from Conexio Genomics since mid-2011. SBT Resolver™ is sold together with the class-leading and broadly-used Assign™ SBT software. We are excited to now introduce several new products from Conexio Genomics, with not only Next Generation Sequencing (NGS) products and Assign™ MPS software, but also the new product Gamma-Type™. Gamma-Type™ is a novel method for typing within the central MHC, specifically the Gamma block, by determining differences of SNPs at 25 locations within this genomic region. You can read more about these products within this issue of Olerup News. We are excited to introduce these new products along with the already established SBT technologies from Conexio.

New Product Line In parallel, Olerup is revitalizing its own product portfolio by developing a product line for real-time PCR-HLA typing. The

development has been driven by the increased demand for faster technology for on-call typing, but will also bring other benefits, with an Olerup spin, to the labs. The plan is to have these products available for RUO testing in Q2 2015 and a CE/IVD-marked product later that year.

The AbSorber product XM-ONE®, an endothelial cell cross match test, is also sold via Olerup and our global sales network. The product was introduced in 2007/2008 and is both CE-marked and FDA 510(k) cleared.

We are pleased that over 20 labs have seen the benefit of this assay to further characterize the risk/role of non-HLA antibodies.

Olerup became part of the Allenex Group in 2008 and is, together with AbSorber (since 2011), located in same facilities in Stockholm. Allenex is a public company listed on the NASDAQ/OMX Stock Exchange market in Stockholm. Allenex is a company committed to the development, manufacture, promotion, and distribution of products for safer transplantation of stem cells and solid organs.

Anders Karlsson CEO of Olerup and Allenex Group

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A new paradigm for matching in HSCT Conventional HLA typing includes loci at only 3 of the 4 major MHC genomic blocks, resulting in potential for haplotype mismatching. MHC haplotype mismatching increases the risk of acute GvHD and likelihood of disease relapse (Petersdorf et al, PLoS Medicine Jan 2007 | Vol 4 | Issue 1. 59-68).

It is well documented that acute GvHD may occur in even the best HLA-matched allogeneic transplants. Realizing that the Gamma

block may be a key locus when predicting haplotype matching, our partner Conexio Genomics, has developed a powerful new addition to the HSCT matching arsenal.

Available Now Available now, Gamma-Type™ is a simple PCR-SSP for 25 SNPs within the Gamma block of the MHC. This block includes the C4, C2 and Bf genes. Collectively, the SNPs

Olerup – the (real) time has come Olerup SSP AB is developing real-time PCR kits for the qualitative detection of HLA alleles. The initial product will target solid organ transplantation and is set to launch in quarter two 2015 for research use only, followed by the launch of CE-marked and FDA 510(k) cleared products later in the year. The Olerup SSP® real-time PCR kits are being developed for use with a range of popular real-time PCR instruments. ”“We at Olerup SSP AB have 20+ years of experience in the design and manufacture of reagents for HLA typing and we will leverage this expertise to introduce new important products for Transplant Laboratories”, says Anna Hedlund, Head of R&D at Olerup SSP AB. “To develop a user-friendly yet advanced product line for more automated HLA typing has been a subject for our development team for some time and it is with great enthusiasm we now move closer to launch”, she continues.

The Technology The highly sensitive real-time PCR technology has unique capacities that fit well with the complexity of HLA, allowing for robust typing from low input DNA concentrations while also reducing the risk of misinterpretation of primer dimers and other PCR artefacts. The software based sample-, interpretation- and result handling will mirror the laboratory workflow and intuitively guide the user to the final result.

Olerup will provide a robust HLA-typing solution with minimal ambiguities whilst retaining plenty of capacity to cope with future allele updates.

“Our objective is to be the overall leader in SSP typing by focusing on usability and flexibility for laboratory staff working daily with our products. This will also be reflected in our new real-time PCR product line”, Anna Hedlund ends. ■

provide a highly polymorphic locus that provides additional MHC information for predicting haplotype matching/mismatching.

Recent studies have shown that GammaType™ mismatches are associated with severe acute GvHD. Given the potential importance of this new matching approach, Conexio will also include the Gamma-Type™ SNP targets in their NGS assay and software strategy (see page 6). ■

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Communication and information – Olerup and the web The first thing you do when you look for information on a product or a company nowadays is probably to Google It. Having easy accessible information on the web is a must.

At Olerup we have constantly developed and improved our web services and today it is

possible to access product details, download software updates, search for LOT documentation, find the nearest distributor and also to purchase products in certain regions. You will also be able to find news about our companies as well as find different meetings where we will be present. This is of course since we believe that easy accessible informa-

tion is required and useful for users of our products. So, if you have not visited our web pages before, please do so and see if it could be of value for you.

Olerup is easiest accessed through www. olerup.com, the portal to our distribution network. As always your feedback is important for us so if you have suggestions on how we could make our presence on the web even better, please let us know. If you think that it is already as good as it can get, please let us know that as well. ■

Complement activation and AECA Several studies have shown that both HLA and non-HLA antibodies play an important role in graft rejection. Recent data also suggests that HLA antibodies that fix and activate complement are clinically more relevant than non-activating antibodies. Less is known about non-HLA antibodies and complement fixation on graft outcome.

In an ongoing EU project ‘EUROSTAM’, within the framework of the European Commission’s 7th framework program,

AbSorber has developed a prototype enabling measurement of complement-fixation by anti-endothelial cell antibodies (AECA).

The extended XM-ONE® prototype provides the original XM-ONE® information whether a patient serum sample contains donor-specific AECA, and in addition also gives information about complement activation by the AECA. The prototype is currently being evaluated by the EUROSTAM partner laboratories

Picture adapted from Fig 1A in “Complement evasion by human pathogens” by John D. Lambris et. al., Nature Reviews Microbiology 6, 132-142 (2008).

The classical complement pathway is triggered by antigen-bound antibody molecules on the cell surface.

Two units of IgG or one IgM antibodies can activate the classical complement pathway. While IgG4 antibodies cannot initiate complement activation, the subclasses IgG3, IgG1, and IgG2 (in this internal order of efficiency) can activate the classical complement pathway. C3b is a complement-split product that is generated and bound to the cell-surface during complement activation. By measuring the binding of C3b on the cell surface, the level of complement activation can be determined.

and the aim is to use the prototype to study the impact of complement activation by AECA on kidney graft outcome in highly sensitized patients. ■ AD

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Setting the benchmark for SSP typing What’s Now Olerup SSP AB takes pride in being a leader in HLA typing with SSP technology. With more than 20 years of experience in primer design and SSP kit development we continue to provide the most up-to-date SSP HLA typing kits on the market. The primers in Olerup SSP® kits are continuously updated in response to allele expansion and each new lot is planned and produced based on the latest released IMGT HLA allele database.

Apart from producing SSP kits with superior quality and resolution we are also dedicated to meet new requirements and requests on product performance and design. Some of our most recent improvements include: • Inclusion of Negative Control (NC) wells in all high resolution kits (beginning with lot “V”) • Extended trays with fewer antigen level ambiguities and resolution of common null alleles are available for HLA-A, HLA-B, HLA-C, and HLA-DR • Simplified SCORE™ short-cut-version

What’s New DQA-DQB-DR Enhanced In direct response to customer feedback, Olerup SSP AB is launching a new Class II SSP tray to provide enhanced typing information catered towards common patient antibody/donor interactions.

The new extended Class II tray will feature: • DRB1, DRB345, and DQB1 low resolution typing with the following enhancements: - Resolution of null alleles; DRB4*01:03N and DRB5*01:08N - Resolution of common DR52 groups, DRB3*01 vs. 02 vs. 03 - Resolution of common DR51 groups, DRB5*01 vs. 02 - Enhanced DRB1 resolution for DRB1*04: DRB1*04:01 vs. 04:02 vs. 04:03 vs. 04:05 vs. 04:07 - Enhanced DRB1 resolution for DRB1*14: DRB1*14:01 vs. 14:54 - Enhanced DQB1 resolution for DQB1*06: DQB1*06:01 vs. 06:02 vs. 06:03 vs. 06:04 vs. 06:09 • High resolution DQA1

What’s Next Real-time PCR Leveraging on more than 20 years of experience with SSP primers, we are pleased to announce that a 384-well RT-PCR HLA Typing product is in our development pipeline.

• HLA-A, B, C, DRB1, DRB345, DQA1, DQB1, DPA1, DPB1 typing • Sophisticated design allowing increased resolution to manage new alleles as they are reported • Platform independent.

For more about Olerup and Real-Time PCR, look at page 3. ■

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NGS – Conexio Genomics Conexio Genomics will begin releasing its next generation HLA sequencing based typing solutions the coming months. The released products will cover all HLA typing applications and also include innovative products for expanded MHC matching.

Long range approach Conexio’s long amplicon approaches will include full length HLA-A, -B-C,-DQB1, DPB1 and exons 2 and 3 for DRB1/3/4 and 5. Unique to these products will be the inclusion of amplicons that span the Gamma-Type™ SNPs, thus providing the first suite of assays that will include typing of loci from all 4 of the MHC major genomic blocks. The Gamma-Type™ amplicons will be multiplexed with the HLA Class I amplicons so that no additional work will be required.

Users will have the option to analyze the The Gamma-Type™ data.

Direct amplicon Conexio will also release direct amplicon assays for exon 2 and 3 of HLA-A, -B, -C and DQB1 and exon 2 of DRB1.

Capture probe Conexio’s unique capture probe based assay

for HLA and transplant related genes will be released after these PCR-based assays. As opposed to enrichment by PCR amplification, DNA fragments that contain HLA are enriched using HLA specific capture probes.

Capture-HLA™ includes a proprietary probe design for HLA and will also include The Gamma-Type™ .

David Sayer, CEO of Conexio adds, “The big advantage of the capture probe assay is that the testing for all genes happens simultaneously in one tube, and additional genes of interest can easily be included with no additional work.”

Data analysis Data from all assays will be analyzed in Assign™ MPS. MPS is simple to use and has the look and feel of all of Conexio’s Assign softwares so that transition from Sanger to Next Gen is simple. MPS enables the visualization of all data and highlights regions that require careful review for potential base call errors. Analysis is rapid and accurate and data from the current major next generation sequencers, including the Ion Torrent, MiSeq and PacBio, can easily be analyzed.

David Sayer, CEO of Conexio Genomics.

DavidofSayer, Subsequent versions MPS, due for release in 2015, will contain the features CEO, Conexio Pty. of all Conexio sequence analysis software. This will enable the analysis of Sanger data and data from practically any genetic system for labs who’s testing repertoire extends beyond HLA. ■

XM-ONE proficiency testing ®

XM-ONE®

This is the fourth year the XM-ONE Proficiency Testing (PT) program is running.

The PT program, being approved by ASHI, is coordinated by Olerup Inc. and is offered to laboratories which are validated and interested in continued surveillance of their XM-ONE® performance. ®

We are pleased to see that the number of participating centers has been increasing every year and look forward to have even more centers aboard in upcoming surveys. It is very satisfying to see that the performance continues to be very high. ■

PT

Date

Centers

Succesfull participation *

2011-I

Sep 2011

5

5/5

2012-I

Feb 2012

10

9/10

2012-II

Sep 2012

15

15/15

2013-I

Mar 2013

15

14/15

2013-II

Sep 2013

17

16/17

2014-I

Apr 2014

17

14/17 **

* ≥ 80% concordance with consensus for each method (IgG or IgM). ** 3/17 centers requested to be considered Educational Participants and were not graded.

The XM-ONE® transplantation cross match test is today primarily used prior kidney transplantation, to detect non-HLA antibodies against the donor’s endothelia. The results of the first clinical trials using XM-ONE®, published in February 2009 in the medical journal Transplantation, indicated that XM-ONE® could predict rejection reactions in patients that were approved for transplants using test methods that are considered standard. Later publications have shown that XM-ONE® is a valuable complement to traditional antibody testing prior organ transplantation.

XM-ONE® is CE marked for sales in Europe and has been cleared by the FDA for sales in the U.S. Read more about XM-ONE® at www.absorber.se.

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Conexio’s sequencing based typing kits for HLA Class I and Class II genes.

Data fully compatible with Assign™ SBT sequence analysis software that includes Conexio’s typing kits for HLA Class I and Class II genes. analysis ofsequencing non-codingbased regions.

Data fully compatible with Assign™ SBT sequence analysis software that includes analysis of non-coding regions. map SBT Resolver™ Amplicon Coverage SBT Resolver™ Resolver™ Amplicon Amplicon Coverage mapExon SBT Coverage map Exon Intron Exon Intron 5’UTR

1

1

2

2

3

Intron 3

Exon Intron Exon Intron Exon Intron Exon Intron Exon 4 4 5 5 6 6 7 7 8

Exon Intron Intron Exon Exon Intron Intron Exon Exon Intron Intron Exon Exon Intron Intron Exon Exon Intron Intron Exon Exon Intron Intron Exon Exon Intron Intron Exon Exon 5’UTR Exon 5’UTR 11 11 22 22 33 33 44 44 55 55 66 66 77 77 88

Class II updates: : Complete sequencing of all exon 3 allele groups in addition to exon 2 Class IIII updates: updates: Class : Complete coverage of exon 2 and exon 3 Complete sequencing sequencing of of all all exon exon 33 allele allele groups groups in in addition addition to to exon exon 22 :: Complete : Complete coverage of exon 1, 3, 4 and 5 in addition to exon 2 Complete coverage coverage of of exon exon 22 and and exon exon 33 :: Complete

Complete coverage coverage of of exon exon 1, 1, 3, 3, 44 and and 55 in in addition addition to to exon exon 22 :: Complete For Research Use Only. Not for use in diagnostic procedures.

No claim or representation is intended to provide information for the diagnosis, prevention, orfor treatment of a disease.

For Research Research Use Use Only. Not Not use in in diagnostic diagnostic procedures.

For Only. for use procedures.

No claim claim or or representation representation is is intended intended to to provide provide information information for for No the diagnosis, prevention, or treatment of a disease.

Designed, developed and manufactured by Conexio the diagnosis, prevention, or treatment of a disease.

Distributed by Distributed by by Distributed www.olerup.com www.olerup.com www.olerup.com

Designed, developed developed and and manufactured manufactured by

by Conexio Conexio Designed,

conexio-genomics.com

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conexio-genomics.com

Pioneering since since 2002 2002 Pioneering

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Olerup Network provides Global Coverage With direct sales in 14 countries and a distributor network covering Europe, Canada, Latin- and South America, Asia, Oceania and parts of Africa, Olerup is truly a Global Provider of transplant diagnostics. During 2013, Olerup added 15 new partners and the growth is expected to continue.

Selecting a distributor To be selected as a distributor of the Olerup Portfolio, distributors need to be considered as established in the field of diagnostics and all distributors are evaluated before being signed up. Both financial status as well as experience within the diagnostic segment are key factors, but also other quality components as, for example, educational level and quality certificates.

Recently BioDist S.A. de C.V. of Mexico was selected as partner and distributor in Mexico. The company has a long history of providing Mexican Laboratories with reagents and equipment and is a company well representing the qualities that Olerup are requesting.

Specialist and Sales Responsible for Nordic and Belgium often interacts with customers to provide support and training.

“Our customers are deeply experienced and knowledgeable within HLA and, overall, are pleased with Olerup’s product performance,” says Bruno. “They recognize Olerup SSP as the leading SSP manufacturer as we continuously update our kits to provide the best quality SSP product available on the market,” he continues. “We maintain a close partnership with our customers, are readily available to help with questions, concerns and offer in house software training and support,” he rounds off.

Head of Technical Support within Olerup Inc, supporting not only the users in the US, but also Mexico and Canada. “We host regular Webex software trainings in SCORE and Assign and make on-site visits to assist and troubleshoot when needed. Though we mainly have very experienced users it is still our goal to provide timely and thorough customer support”. ■

“We continuously monitor our customer satisfaction levels and try to stay on top of all our customers’ needs. In the competitive environment we are in, it is important that we provide state-of-the-art support to the users of our products” says Marilyn Wetmore,

Olerup provides QA and Regulatory services for its distributor network and regulatory approval for the different product lines is being applied for in numerous countries such as China and Brazil. Technical Training and Support are provided to ensure both high quality and timely support when necessary. Bruno Vanherberghen, Technical

OLE-141014B-1

From production to use “We were delighted to be selected as a distributor for the Olerup product portfolio and we look forward to provide the products to the Mexican Market”, says Rebeca Miramontes, CEO de Biodist, SA de CV. “The products are already included in this year’s tenders here in Mexico and we expect to be very successful. This we base upon the quality of the products provided but also on the great reputation Olerup has here in Mexico” she continues.

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