Product Catalog. HDx Reference Standards Identify and Control Variability Every Day. HORIZON DIAGNOSTICS

Transcription

1 HORIZON DIAGNOSTICS Product Catalog For Research Use Only HDx Reference Standards Identify and Control Variability Every Day

2 Independent External Controls Sanger, NGS, qpcr, FISH, IHC, cfdna, RNA Assays Supported Routinely monitor the performance of your workflows and assays Point mutations, Deletions, Translocations and CNVs available DNA and FFPE based controls covering >80 onco-specific mutations For Research Use Only Redefining Reference Standards Horizon Diagnostics, a business unit of Horizon Discovery Group plc, is a leading provider of genetically defined, human genomic Reference Standards, including FFPE cell line sections, DNA, Cell-free DNA, Fluorescence In-Situ Hybridization (FISH) and Immunohistochemistry (IHC) Slides. These standards offer a sustainable source of reference material to laboratories, proficiency schemes and manufacturers, providing an unprecedented level of control. Genomic DNA FFPE Sections Formalin-Compromised DNA FFPE Slides Cell Free DNA (cfdna) 2 FFPE Blocks

3 100% Confidence in your Results for $1.20 per assay Based on an assay using 10ng BRAF V600E EGFR T790M EML4-ALK Workflow Variability Each step in the tumor genotyping process is prone to error-causing variability, including operator training, instrument to instrument variability, extraction efficiency and system calibration. In practice calibration is seldom performed, leading directly to challenges in the reliability of results. Even when attempts are made to standardize, the controls used are themselves unreliable. Precisely Defined Mutations to Routinely Monitor your Workflow The need for standardized, renewable reference material has also made it particularly challenging for external quality assurance programs to accurately monitor and regulate genotyping accuracy. It is due to the multiple sources of variability there is a significant baseline error rate. Horizon s Diagnostics division was founded to directly address this problem by developing tools that enable scientists, and ultimately clinicians, to quantify, monitor and reduce genotyping error. Identify and Control Variability Every Day 3

4 The Problem Each step in the tumor genotyping process is prone to error-causing variability Sample Quality Sample fixation processes are highly variable and will impact on the quality of the extractable DNA. High-grade formalin for a short time (i.e. less than 24 hours) will preserve the quality of DNA within the samples and provide a greater DNA yield compared to Low-grade formalin for a longer time (i.e. more than 24 hours). DNA Extraction The quality and quantity of DNA can vary widely depending on the extraction method/kit used. Platform Variability The limit of detection of a molecular diagnostic assay can vary from 1% to 25%. This is dependent on the assay design as well as the platform choice. Not all platforms are capable of distinguishing between subtle nucleic acid changes. DNA Quantification Success or failure in DNA analysis applications often comes down to whether or not the appropriate amount of nucleic acid is used in the analysis and if the quality of that nucleic acid is sufficient. There are many methods available, each with its own strengths and weaknesses. The Solution Routinely monitor the performance of your assays provide highly characterized and precisely defined DNA for use in laboratories to identify pre- or postanalytical errors. They are ideal for the routine monitoring of your workflow with pre-validated and pre-defined quantities of DNA, copy number and allelic frequency that replicates typical tumor genetics. Establish and validate the true sensitivity and specificity of your assay through the routine use of today. cfdna HDx Reference Standards FFPE HDx Reference Standards Formalin- Compromised DNA DNA HDx Reference Standards Sample Quality DNA Extraction DNA Quantification Liquid Biopsy Platform Variability Identify and Control Variability Every Day Analysis & Review Sample Heterogeneity FISH HDx Reference Standards IHC HDx Reference Standards For Research Use Only Probe Choice Antibody Choice 4

5 Supporting Assays Worldwide of participating laboratories in 2014 worldwide Proficiency Testing Scheme (External Quality Assurance) reported false-negative or false-positive EGFR 28%testing results [Oncologist 2014;16:467 78] We are Working With Over 700 Laboratories, Proficiency Testing Schemes and Platform Developers Worldwide Variability in DNA extraction from tumor biopsies and a lack of standardization are currently major sources of error in molecular laboratories. The availability of genetically defined reference materials provides an industry standard for development and quality control of molecular and antibody-based assays, directly improving their accuracy. Horizon Diagnostics suite of reference material includes standards for the increasing number of rare mutations being targeted for cancer therapeutics, which by definition are hard to find in clinical samples. These standards have been made available in a variety of formats including genomic DNA aliquots, Formalin-Fixed Paraffin- Embedded (FFPE) sections, Fluorescent In-Situ Hybridization (FISH) slides, Immunohistochemistry (IHC) slides and Cell Free DNA (cfdna). are already having a profound impact on the molecular labs that have adopted them to: Validate the sensitivity and Limit of Detection (LOD) of assays Routinely calibrate the sensitivity of assays in order to maintain quality control Control pre-analytical processes, including DNA extraction and quantitation using in-process standards Compare assay performance between platforms, assays and users from a common reference point Support raising standards through providing materials for staff training and proficiency schemes Identify and Control Variability Every Day 5

6 Product Applications are precisely defined for routine monitoring of applications as listed below: 1 2 Sanger and qpcr Sequencing Routine monitoring of analytical performance for both specificity and sensitivity Establish and determine the absolute limit of detection Independent assay verification Assay and platform optimization Next Generation Sequencing (NGS) Validate your NGS platform and assay Analyze and evaluate variant calling sensitivity Accurately quantify the limit of detection for each variant Utilize the breadth of variants to understand assay specificity 3 4 Fluorescence In-Situ Hybridization (FISH) FISH assay performance monitoring DNA probe validation Silver and Chromogenic In-Situ Hybridization (SISH & CISH) and other related techniques Training and evaluation of cytogeneticists Immunohistochemistry (IHC) A consistent and renewable source of precisely defined protein expression Cores containing biomarker specific negative and positive protein expressing cell lines on the same slide Standardization and verification of IHC workflows New Cell Free DNA (cfdna) Launch Develop and validate new cfdna assays with fragmented standards Evaluate the sensitivity and specificity of your cfdna assay Quantify the limit of detection for multiple variants with a range of low allelic frequencies To order custom-made reference standards info@horizondiscovery.com 6

7 s are available in the formats listed below: Genomic DNA Validated allelic frequency using digital PCR Precisely validated allelic frequency [50%] Allelic frequency can be diluted as required Highly consistent renewable resource Independent assay validation & routine monitoring of analytical performance for both specificity & sensitivity FFPE Sections Consistent allelic frequency throughout FFPE block Range of precisely validated allelic frequencies [1%-50%] Standards mimic cancer patient genetics & processed tissue sample quality Test the integrity of a molecular assay workflow [extraction, quantification, molecular testing & data analysis] Concentration 1μg 50ng / μl Extractable DNA 1 FFPE Section 400ng - 700ng Formalin-Compromised DNA Fragmentation profiled by Tapestation Assay Range of precisely validated allelic frequencies [1-25%] Standards mimic the impact of formalin DNA format extracted from formalin-treated cells to be placed straight into the assay Genome In A Bottle FFPE Sections Highly Characterized FFPE Reference Standards for your NGS Workflow Compare your data with the community as part of the Personal Genome Project (PGP) Coverage of over 99.5% of genes with clinical testing available Concentration 1μg 50ng / μl Extractable DNA 1 FFPE Section ng Cell Free DNA (cfdna) Reference standard to aid the assessment and validation of cfdna assays Available as fragmented cell line DNA to an average size of 160bp Allelic frequency and gene copy number validated with ddpcr Multiplex and Singleplex versions available FFPE Slides Consistent source of slides containing precisely defined protein expression levels/ chromosomal abnormalities Multicore FFPE sections containing positive and negative cell lines for FISH and IHC assays Extensively characterized cell lines using molecular assays, IHC, Western Blot and FISH Concentration 4x350ng 40ng / μl 5 FFPE Slides FFPE Blocks Consistent source of slides containing precisely defined protein expression levels/chromosomal abnormalities Customizable options - choose your biomarkers of interest Cost effective for routine adoption Complete control from sectioning to reporting Identify and Control Variability Every Day 7

8 1 Base-Seq Sanger and qpcr Sequencing For Research Use Only Identify and Control Variability in your Workflow Routinely monitor your workflow using Pre-Analytical DNA Extraction DNA Quantitation Sequencing qpcr These standards are independently validated with a broad range of molecular assays to ensure consistency Validation Test Allelic Frequency Gene Copy Number Genotype Quantification Assay Droplet Digital PCR Droplet Digital PCR Sanger Sequencing of locus specific PCR Spectrophotometric assay (DNA)/Quantifluor (FFPE-extracted DNA) 8

9 Formats and Pricing Pre-Analytical Formalin-Fixed, Paraffin-Embedded (FFPE) Reference Standards Consistent Allelic Frequency throughout FFPE block Range of precisely validated allelic frequencies [1%, 5%, 20% and 50%] Standards mimic cancer patient genetics & processed tissue sample quality Test the full integrity of a molecular assay workflow [extraction, quantification, molecular testing & data analysis] FFPE Pricing 1 Section $100/section 5 Sections $60/section 10 Sections $50/section 20 Sections $40/section 1 FFPE Section Extractable DNA 400ng - 700ng Analytical DNA Reference Standards Validated allelic frequency using digital PCR Generate the absolute Limit of Detection (LOD) with Mutant and Wild Type DNA Allelic frequency can be modified as required. Highly consistent renewable resource Independent assay validation & routine monitoring of analytical performance for both specificity & sensitivity DNA Pricing 1 Vial $120 1μg Concentration 50ng / μl DNA Volume 1μg, WT - 5μg Identify and Control Variability Every Day 9

10 Base-Seq Sanger and qpcr Sequencing You can order online: or Tel: +44 (0) Mutation Format Number of Uses* Allelic Frequency Catalog ID ABL1 ABL1 T315I DNA % HD656 ABL1 Wild Type DNA % HD657 AKT1 AKT1 E17K DNA % HD658 AKT1 E17K FFPE 50% HD167 AKT1 Wild Type DNA % HD659 AKT1 Wild Type FFPE 100% HD172 ALK ALK F1174L DNA % HD660 ALK Wild Type DNA % HD661 BRAF BRAF V600E DNA % HD238 BRAF V600E FFPE 1% HD273 BRAF V600E FFPE 5% HD705 BRAF V600E FFPE 20% HD232 BRAF V600E FFPE 50% HD598 BRAF V600G DNA % HD244 BRAF V600K DNA % HD239 BRAF V600K FFPE 1% HD274 BRAF V600K FFPE 5% HD123 BRAF V600K FFPE 50% HD268 BRAF V600M DNA % HD246 BRAF V600R DNA % HD248 BRAF V600R FFPE 50% HD275 BRAF Wild Type DNA % HD249 BRAF Wild Type FFPE 100% HD266 EGFR EGFR S492R (EGFR G719S) DNA % HD663 EGFR S492R (EGFR G719S) FFPE 33% Contact us EGFR G719A DNA % HD262 EGFR G719A FFPE 50% Contact us EGFR G719S DNA % HD253 EGFR G719S FFPE 5% HD714 EGFR G719S FFPE 33% HD179 EGFR G719S FFPE 50% HD230 EGFR ΔE746-A750 DNA % HD251 EGFR ΔE746-A750 FFPE 5% HD653 EGFR ΔE746-A750 FFPE 50% HD308 EGFR S768I FFPE 50% HD707 EGFR S768I DNA % HD261 EGFR V769_D770insASV DNA % HD260 EGFR V769_D770insASV FFPE 50% HD706 EGFR T790M DNA % HD258 EGFR T790M FFPE 6.5% HD125 EGFR T790M FFPE 20% HD126 EGFR T790M FFPE 50% HD127 EGFR T790M/L858R FFPE 80% HD234 EGFR L858R DNA % HD254 EGFR L858R FFPE 5% HD129 EGFR L858R FFPE 20% HD130 EGFR L858R FFPE 50% HD131 EGFR L861Q DNA % HD257 EGFR L861Q FFPE 5% HD132 EGFR L861Q FFPE 50% HD133 EGFR Wild Type DNA % HD709 EGFR Wild Type FFPE 100% HD141 10

11 Base-Seq Sanger and qpcr Sequencing You can order online: or Tel: +44 (0) Mutation Format Number of Uses* Allelic Frequency Catalog ID EML4-ALK EML4-ALK Translocation Variant 1 DNA % HD664 FGFR2 FGFR2 S252W DNA % HD665 FGFR2 Wild Type DNA % HD666 FLT3 FLT3 D835Y DNA % HD668 FLT3 I836 DNA % HD667 FLT3 Wild Type DNA % HD669 GNA11 GNA11 Q209L DNA % HD670 GNA11 Wild Type DNA % HD671 GNAQ GNAQ Q209L DNA % HD672 GNAQ Wild Type DNA % HD673 GNAS GNAS R201C DNA % HD674 GNAS Wild Type DNA % HD675 IDH1 IDH1 R132C DNA % HD676 IDH1 R132H DNA % HD677 IDH1 Wild Type DNA % HD678 IDH2 IDH2 R140Q DNA % HD679 IDH2 R172K DNA % HD680 IDH2 Wild Type DNA % HD681 JAK2 JAK2 V617F DNA % HD649 JAK2 Wild Type DNA % HD652 KIT KIT D816V DNA % HD654 KIT Wild Type DNA % HD655 KRAS KRAS G12A DNA % HD265 KRAS G12A FFPE 5% HD117 KRAS G12A FFPE 50% HD255 KRAS G12C DNA % HD269 KRAS G12C FFPE 5% HD159 KRAS G12C FFPE 50% HD256 KRAS G12D DNA % HD272 KRAS G12D FFPE 5% HD119 KRAS G12D FFPE 50% HD204 KRAS G12R DNA % HD287 KRAS G12R FFPE 5% HD118 KRAS G12R FFPE 50% HD207 KRAS G12S DNA % HD288 KRAS G12S FFPE 50% HD120 KRAS G12S FFPE 50% HD210 KRAS G12V DNA % HD289 KRAS G12V FFPE 5% HD116 KRAS G12V FFPE 50% HD213 KRAS G13D DNA % HD290 KRAS G13D FFPE 5% HD113 KRAS G13D FFPE 50% HD216 Identify and Control Variability Every Day 11

12 Base-Seq Sanger and qpcr Sequencing You can order online: or Tel: +44 (0) Mutation Format Number of Uses* Allelic Frequency Catalog ID KRAS A59T DNA % HD694 KRAS Q61H DNA % HD291 KRAS Q61H FFPE 50% HD94 KRAS Q61L DNA % HD298 KRAS Q61L FFPE 50% HD140 KRAS A146T DNA % HD299 KRAS A146T FFPE 50% HD580 KRAS Wild Type DNA % HD710 KRAS Wild Type FFPE 100% HD135 MEK MEK P124L DNA % HD698 MEK Wild Type DNA % HD699 MET MET Y1253D DNA % HD682 MET Wild Type DNA % HD683 NOTCH NOTCH1 L1601P DNA % HD559-1µg NOTCH1 Wild Type DNA % HD464-5µg NRAS NRAS G12D DNA % HD695 NRAS G12D FFPE 50% HD745 NRAS G12V DNA % HD302 NRAS G12V FFPE 50% HD203 NRAS G13D DNA % Contact us NRAS G13D FFPE 50% HD746 NRAS A59T DNA % HD697 NRAS Q61H DNA % HD303 NRAS Q61H FFPE 50% HD581 NRAS Q61K DNA % HD351 NRAS Q61K FFPE 50% HD247 NRAS Q61L DNA % HD412 NRAS Q61L FFPE 50% HD349 NRAS Q61R DNA % HD574 NRAS Q61R FFPE 50% HD286 NRAS K117N DNA % HD696 NRAS A146T DNA % HD757 NRAS A146T FFPE 50% HD580 NRAS Wild Type DNA % HD648 NRAS Wild Type FFPE 100% HD322 PDGFRA PDGFRA D842V DNA % HD686 PDGFRA Wild Type DNA % HD687 PI3KCA PI3KCA E542K DNA % HD688 PI3KCA E542K FFPE 50% HD121 PI3KCA E545K DNA % HD689 PI3KCA E545K FFPE 50% HD112 PI3KCA H1047R DNA % HD690 PI3KCA H1047R FFPE 50% HD599 PI3KCA Wild Type DNA % HD691 PI3KCA Wild Type FFPE 100% HD320 PTEN PTEN ex6/ex7 DNA % HD692 PTEN Wild Type DNA % HD693 12

13 Base-Seq Sanger and qpcr Sequencing You can order online: or Tel: +44 (0) Pack Format Number of Vials Price ($) Catalog ID QIAGEN EGFR Exons 19, 20 & 21 DNA HD 2101-DNA ΔE746-A750, T790M, L858R, L861Q and Wild Type (x2) per vial QIAGEN EGFR Exons 19, 20 & 21 FFPE HD 2101-FFPE ΔE746-A750, T790M, L858R, L861Q and Wild Type (x4) 60 per vial QIAGEN KRAS Codons 12 & 13 DNA & FFPE HD 2100 DNA: G12A, G12C, G12D, G12R, G12S, G12V, G13D & Wild Type (x2) FFPE: G12A, G12C, G12D, G12R, G12S, G12V, G13D & Wild Type per vial QIAGEN KRAS Codons 12 & 13 DNA HD 2100-DNA G12A, G12C, G12D, G12R, G12S, G12V, G13D & Wild Type (x2) per vial QIAGEN KRAS Codons 12 & 13 FFPE HD 2100-FFPE G12A, G12C, G12D, G12R, G12S, G12V, G13D & Wild Type 60 per vial EGFR Exons DNA HD EGFR-DNA-PACK G719S, ΔE746-A750, T790M, L858R, L861Q and Wild Type (x2) per vial EGFR Exons FFPE HD EGFR-LOD-FFPE-PACK G719S, ΔE746-A750, T790M, L858R, L861Q and Wild Type (x5) 50 per vial BRAF Codon 600 FFPE HD BRAF-FFPE-PACK V600E, V600K, V600R and Wild Type 80 per vial KRAS Codons 12, 13, 61 & 146 DNA HD KRAS-DNA-PACK G12A, G12C, G12D, G12R, G12S, G12V, G13D, Q61H, A146T & Wild Type (x2) per vial KRAS Codons 12, 13, 61 & 146 FFPE HD KRAS-FFPE-PACK G12A, G12C, G12D, G12R, G12S, G12V, G13D, Q61H, A146T & Wild Type 48 per vial KRAS Codons 12, 13, 61 & 146 DNA & FFPE HD KRAS-LOD-PACK DNA: G12A, G12C, G12D, G12R, G12S, G12V, G13D, Q61H, A146T & Wild Type (x2) FFPE: G12A, G12C, G12D, G12R, G12S, G12V, G13D, Q61H, A146T & Wild Type per vial All Mutant DNA vials are 1μg, Wild Type are 5μg and FFPE Reference Standards contain between ng extractable DNA dependent on the extraction method. Horizon s Genomic DNA & FFPE Reference Standard packs are ideal for validating the performance of your molecular assays on a daily or weekly basis. Each vial is pre-mixed providing a genetically defined allelic frequency precisely verified using digital PCR. * Based on a 1:10 dilution with an assay using 10ng FFPE Reference Standards contain between ng extractable DNA dependent on the extraction method Identify and Control Variability Every Day 13

14 2. Q-Seq Next Generation Sequencing For Research Use Only Identify and Control Variability in your Workflow Routinely monitor your workflow using Pre-Analytical DNA Extraction Library Preparation Sequencing Products Available Tru-Q Quantitative Multiplex Gene-Specific Structural Multiplex Genome In A Bottle Cell Free DNA (cfdna) Available as DNA to include directly alongside test samples 40 oncospecific variants at 5%, 2.5% and 1% for LOD determination Available as DNA, Formalin- Compromised DNA or FFPE samples Covers 11 oncorelevant variants across 6 genes commonly mutated in cancer Allelic frequency range from % to allow routine validation of your assay performance Available as DNA or FFPE samples KRAS and EGFR specific multiplex available including several commonly identified variants Titratable as a result of single parental background to give multiple allelic frequencies of the same multiplex Available as DNA Includes difficult-tosequence variants such as large INDELs, copy number variants, translocations, and variants in high/low GC content regions Seamlessly integrates into any whole-genome, whole-exome, custom capture or targeted amplicon library kit to challenge and optimize your specific workflow Whole genome reference material derived from the Genome In A Bottle (GIAB) Consortium products Over 2.5 billion bases extensively covered Available as fragmented cell line DNA to an average size of 160bp Mutations provided in a range from very low allelic frequency to 5% and a matched wild type Define the Limit of Detection (LOD) of your assays and platforms Multiplex and Singleplex versions available 14

15 Formats and Pricing Pre-Analytical Formalin-Fixed, Paraffin-Embedded (FFPE) Reference Standards Consistent Allelic Frequency throughout FFPE block Range of precisely validated allelic frequencies [1%, 5%, 20% and 50%] Standards mimic cancer patient genetics & processed tissue sample quality Test the full integrity of a molecular assay workflow [extraction, quantification, molecular testing & data analysis] FFPE Pricing 1 Section $100/section 5 Sections $60/section 10 Sections $50/section 20 Sections $40/section 1 FFPE Section Extractable DNA 400ng - 700ng Analytical DNA Reference Standards Validated allelic frequency using digital PCR Generate the absolute Limit of Detection (LOD) with matched Mutant and Wild Type DNA Allelic frequency can be modified as required. Independent assay validation & routine monitoring of analytical performance for both specificity & sensitivity DNA Pricing Mutant Wild Type Concentration $240 /1μg $120/5μg 1μg 50ng / μl Identify and Control Variability Every Day 15

16 Formats and Pricing Continued Analytical Formalin-Compromised DNA Reference Standards Fragmentation profiled by Tapestation Assay Range of precisely validated allelic frequency [1-25%] Standards mimic the impact of formalin Two available tiers of formalin intensity DNA Pricing Mutant Concentration $240 /1μg 1μg 50ng / μl Pre-Analytical Genome In A Bottle (GIAB) FFPE Sections Highly Characterized FFPE Reference Standards for your NGS Workflow Compare your data with the community as part of the Personal Genome Project (PGP) Coverage of over 99.5% of genes with clinical testing available GIAB Pricing FFPE Section Extractable DNA $10 /Section 10 FFPE Sections 400ng - 700ng For more information contact us at info@horizondiscovery.com 16

17 Q-Seq Next Generation Sequencing You can order online: or Tel: +44 (0) Mutation Format Allelic Frequency (%) Concentration (ng/μl) Catalog ID Multiplex Quantitative Multiplex DNA -- 1μg 50ng/μl HD701 Quantitative Multiplex FFPE HD200 Quantitative Multiplex Formalin-Compromised DNA I Mild* 1μg 50ng/μl HD749 Quantitative Multiplex Formalin-Compromised DNA II Severe** 1μg 50ng/μl HD751 Gene Specific Mulitplex EGFR-Specific Multiplex DNA μg 50ng/μl HD748 EGFR-Specific Multiplex FFPE 5 -- HD300 EGFR-Specific Multiplex FFPE 1 -- HD850 EGFR Wild Type DNA 100 5μg 50ng/μl HD709 KRAS-Specific Multiplex DNA μg 50ng/μl HD900-1μg KRAS-Specific Multiplex FFPE 5 -- HD301 KRAS Wild Type DNA 100 5μg 50ng/μl HD212 Tru-Q Tru-Q 1 (5% Tier) DNA 5 1μg 50ng/μl HD728 Tru-Q 2 (5% Tier) DNA 5 1μg 50ng/μl HD729 Tru-Q 3 (5% Tier) DNA 5 1μg 50ng/μl HD730 Tru-Q 4 (5% Tier) DNA 5 1μg 50ng/μl HD731 Tru-Q 5 (2.5% Tier) DNA 2.5 1μg 50ng/μl HD732 Tru-Q 6 (2.5% Tier) DNA 2.5 1μg 50ng/μl HD733 Tru-Q 7 (1.25% Tier) DNA μg 50ng/μl HD734 Structural Multiplex Structural Multiplex DNA -- 1μg 50ng/μl HD728 Genome In A Bottle GIAB - Ashkenazim PGP Father FFPE GM24149 GIAB - Ashkenazim PGP Mother FFPE GM24143 GIAB - Ashkenazim PGP Son FFPE GM24385 GIAB - Asian PGP Son FFPE GM24631 To view the full mutation lists for each product, visit * Mild - This product is lightly treated with formalin ** Severe - This product is severely treated with formalin FFPE Reference Standards contain between ng extractable DNA dependent on the extraction method Identify and Control Variability Every Day 17

18 3. 2. Q-Seq FISH Next Fluorescence Generation In-Situ Sequencing Hybridization For Research Use Only Identify and Control Variability in your Workflow Routinely monitor your workflow using Key Applications Assay optimization and performance monitoring A renewable and consistent point of reference when optimizing and monitoring the performance of your assay Probe evaluation Guide the evaluation of probes based on their sensitivity and specificity On slide control Place your sample alongside and provide confidence to your FISH result These standards are independently validated with a broad range of assays to ensure consistency Validation Test Genomic aberration Assay FISH 18

19 Formats and Pricing Biomarker Specific Reference Standards Extensively characterized cell lines FFPE Pricing 5 Slides $20/slide 250+ Slides $16/slide Defined cores containing a positive and negative chromosomal aberrations for a single biomarker on the same slide Ideal for every day performance monitoring for single biomarker assays _ + 5 Slides per pack Multimarker Reference Standards FFPE Pricing Extensively characterized cell lines 5 Slides $40/Slide Defined cores containing positive and negative aberrations for multiple biomarkers on the same slide 250+ Slides $32/Slide Provides multiple negative and positive controls per biomarker Ability to optimize probes on multiple independent cell lines 5 Slides per pack FFPE Block FFPE Pricing Customizable FFPE blocks Available as either Biomarker or Multimarker blocks Biomarker Block $5,000 Multimarker Block $10,000 Customizable options - choose your biomarkers of interest Cost effective for routine adoption Complete control from sectioning to reporting 0.5cm (~500 3μm sections) Identify and Control Variability Every Day 19

20 FISH Fluorescence In-Situ Hybridization You can order online: or Tel: +44 (0) Mutation Type Mutation Type Format Size Catalog ID EML4-ALK Biomarker Translocation FFPE Slides 5 Slides HD 719 EML4-ALK Biomarker Translocation FFPE Block 0.5cm HD 736 ERBB2 (HER2) Biomarker Translocation FFPE Slides 5 Slides HD763 ERBB2 (HER2) Biomarker Translocation FFPE Block 0.5cm HD764 MET Biomarker Amplification FFPE Slides 5 Slides HD 723 MET Biomarker Amplification FFPE Block 0.5cm HD 740 RET Biomarker Translocation FFPE Slides 5 Slides HD725 RET Biomarker Translocation FFPE Block 0.5cm HD741 ROS1 Biomarker Translocation FFPE Slides 5 Slides HD 727 ROS1 Biomarker Translocation FFPE Blocks 0.5cm HD 742 Lung Panel Multimarker EML4-ALK, MET, RET & ROS1 FFPE Slides 5 Slides HD 717 Lung Panel Multimarker EML4-ALK, MET, RET & ROS1 FFPE Block 0.5cm HD 735 Stained FISH ROS1 Translocation Upcoming FISH HDx Reference Standards Upcoming Genotypes BCR-ABL PML-RARA EML4-ALK Variant 3 CD74-ROS1 More... Contact us at info@horizondiscovery.com for availability 20

21 Reference Standards Identify and Control Variability Every Day by Horizon Diagnostics identify and control variabilty every day. Routine adoption of enables the operator to optimize their laboratory s workflows and assays. Assay, Platform or Workflow Improvements* Routine use of HDx Reference Standards Pricing - HDx Reference Standards Mutant DNA Wild Type DNA cfdna FFPE FFPE Slides From $120/1µg From $120/5µg $340/µg From $40/section From $16/slide * Internal Data, Horizon Diagnostics Non-US prices available Identify and Control Variability Every Day 21

22 4. IHC Immunohistochemistry For Research Use Only Identify and Control Variability in your Workflow Routinely monitor your workflow using Key Applications Assay optimization and performance monitoring A renewable and consistent point of reference when optimizing and monitoring the performance of your assay Antibody evaluation Guide the evaluation of antibodies based on their sensitivity and specificity On slide control Place your sample alongside and provide confidence to your IHC result Validation Test Protein Expression Positive and Negative Cell Line Cores Assay Confirmed using biomarker specific IHC assay Assessed using Quantitative Digital Pathology (QDP) - Visiopharm 22

23 Formats and Pricing Biomarker Specific Reference Standards Extensively characterized cell lines by IHC and QDP Defined cores containing a positive and negative protein expressing cell lines for a single biomarker on the same slide Ideal for every day performance monitoring for single biomarker assays _ ++ FFPE Pricing 5 Slides $20/slide 250+ Slides $16/slide 5 Slides per pack Multimarker Reference Standards Extensively characterized cell lines by IHC and QDP Defined cores containing positive and negative protein expression for multiple biomarkers on the same slide Provides multiple negative and positive controls per biomarker Ability to optimize antibodies on multiple independent cell lines FFPE Pricing 5 Slides $40/Slide 250+ Slides $32/Slide 5 Slides per pack FFPE Block Customizable FFPE sections Available as either Biomarker or Multimarker blocks Customizable options - choose your biomarkers of interest Cost effective for routine adoption Complete control from sectioning to reporting FFPE Pricing Biomarker Block $5,000 Multimarker Block $10, cm (~500 3μm sections) Identify and Control Variability Every Day 23

24 IHC Immunohistochemistry You can order online: or Tel: +44 (0) Mutation Type Mutation Type Format Size Catalog ID ALK Biomarker Translocation FFPE Slides 5 Slides HD718 ALK Biomarker Translocation FFPE Block 0.5cm HD736 BRAF V600E Biomarker SNP FFPE Slides 5 Slides HD720 BRAF V600E Biomarker SNP FFPE Block 0.5cm HD737 EGFR Biomarker Amplification FFPE Slides 5 Slides HD721 EGFR Biomarker Amplification FFPE Block 0.5cm HD738 MET Biomarker Amplification FFPE Slides 5 Slides HD722 MET Biomarker Amplification FFPE Block 0.5cm HD739 ROS1 Biomarker Translocation FFPE Slides 5 Slides HD726 ROS1 Biomarker Translocation FFPE Block 0.5cm HD742 CD274 (PD-L1) Biomarker Expression FFPE Slides 5 Slides HD765 CD274 (PD-L1) Biomarker Expression FFPE Block 0.5cm HD766 MKI67 (Ki-67) Biomarker Expression FFPE Slides 5 Slides HD761 MKI67 (Ki-67) Biomarker Expression FFPE Block 0.5cm HD762 Lung Panel Multimarker EML4-ALK, MET, EGFR & ROS1 FFPE Slides 5 Slides HD716 Lung Panel Multimarker EML4-ALK, MET, EGFR & ROS1 FFPE Block 0.5cm HD735 Stained IHC MET Amplification Upcoming IHC HDx Reference Standards Upcoming Genotypes ER PR HER Ki67 Negative CD4 CD3 CD8 CD20 EML4-ALK Variant 3 More... Contact us at info@horizondiscovery.com for availability 24

25 cfdna Reference Standards Prove Your Performance Cell-free DNA Assay Development done right using HDx Reference Standards Looking to demonstrate the performance of your cfdna assay? Then benchmark it against a set of reliable known controls, and Horizon s first in class cfdna reference standards can help. Let us be your partner, and help you to get the data you need to prove your performance. Identify and Control Variability Every Day 25

26 Cell Free DNA (cfdna) cfdna Applications For Research Use Only Identify and Control Variability in your Workflow Routinely monitor your workflow using Key Applications Develop and validate new cfdna assays at low allelic frequencies Evaluate the sensitivity and specificity of your cfdna assay Low allelic frequencies and matched wild type available These standards are independently validated with a broad range of molecular assays to ensure consistency Validation Test Allelic Frequency Gene Copy Number Genotype Fragmentation Size Quantification Assay Droplet Digital PCR Droplet Digital PCR Sanger Sequencing of locus specific PCR D1000 DNA ScreenTape assay Qubit dsdna BR Assay (post-fragmentation) 26

27 New Launch Formats and Pricing Single Mutation Set Validated allelic frequency using ddpcr Available as fragmented cell line DNA to an average size of 160bp Range of allelic frequencies [0.1%, 1%, 5%] with a matched wild type Information on copy number concentration provided Set of four inclusive of 3 vials representing range of the mutant allelic frequencies and 1 vial of wild type Pricing 4 Vials $480 4x350ng Concentration 40ng / μl Multiplex Set Validated allelic frequency using ddpcr Pricing 4 Vials $480 Available as fragmented cell line DNA to an average size of 160bp Range of allelic frequencies [0.1%, 1%, 5%] with a matched wild type Information on copy number concentration provided Set of four inclusive of 3 vials representing range of the mutant allelic frequencies and 1 vial of wild type Concentration 4x350ng 40ng / μl Identify and Control Variability Every Day 27

28 Formats and Pricing Continued Name Format Mutations Allelic Frequency (%) BRAF V600E cfdna Reference Standard Set Concentration (ng/μl) HD781 Catalog ID Vial 1 cfdna BRAF V600E Wild Type 350ng 40ng/μl Vial 2 cfdna BRAF V600E 5 350ng 40ng/μl Vial 3 cfdna BRAF V600E 1 350ng 40ng/μl Vial 4 cfdna BRAF V600E ng 40ng/μl Multiplex cfdna Reference Standard Set Vial 1 cfdna EGFR, KRAS, NRAS, PIK3CA Wild Type 350ng 40ng/μl HD780 Vial 2 cfdna EGFR, KRAS, NRAS, PIK3CA 5 350ng 40ng/μl Vial 3 cfdna EGFR, KRAS, NRAS, PIK3CA 1 350ng 40ng/μl Vial 4 cfdna EGFR, KRAS, NRAS, PIK3CA ng 40ng/μl Visit for more information 28

29 Product Pipeline Horizon supports the routine monitoring of molecular assays (Sanger Sequencing, qpcr, NGS amongst others) and molecular profiling methods (FISH) across lab developed tests/homebrew workflows and commercially available kit methods. To support the identification of new biomarkers we continue to develop new mutations and expand our current reference standards portfolio. On top of this we are passionate about standardizing additional platforms and workflows (e.g. IHC, cfdna,...) and are actively developing new reference standards to standardize these assays Q Q2 RNA Reference Standards Gene expression analysis has been widely adopted in research and clinical settings. Quantitative assessment of technical performance and systematic RNA sequencing errors are important to understand. Quantitative RNA Reference Standards covering KRAS, BRAF, NRAS, EGFR and Non-Small-Cell Lung Carcinoma (NSCLC) specific translocations (ROS1, RET, EML4-ALK) are currently being developed. Learn more and be a part of upcoming programs contact us: info@horizondiscovery.com Structural Cell Free (cfdna) Reference Standards cfdna allows non-invasive detection of tumor related genetic (and epigenetic) changes that are relevant to cancer development. A plethora of protocols have been adopted for cfdna extraction and sample analysis and each has its own challenges. Low levels of cfdna carrying the mutation of interest and the abundance of wildtype DNA fragments challenge the limit of detection, the sensitivity and specificity of detection methods. Defined and consistent cfdna Reference Standards containing translocations, InDels and copy number variations will enable the standardization and validation of these platforms. Our Standards are manufactured under a Quality Management System which complies with ISO Standards 9001 and to produce specific, consistent and sustainable Reference Standards Our Quality are fully characterized to guarantee the quality, specificity and consistency of each batch. Production Our Consistency offer a reliable, consistent and continually renewable source of genetic material Our Knowledge Utilizing our precision Gene-editing Technology, Horizon is able to precisely engineer mutations into its HDx Reference Standards 29

30 Contact Your Local Representative Horizon Discovery has established global coverage: North Americas Samantha Yuill Phone: s.yuill@horizondiscovery.com Jeff Dale Phone: + 1 (314) j.dale@horizondiscovery.com Europe and UK Louisa Ludbrook Phone: +44 (0) l.ludbrook@horizondiscovery.com Manuela Saathoff Phone: +44 (0) m.saathoff@horizondiscovery.com India and Middle East Narinder Singh Phone: +91(0) n.singh@horizondiscovery.com Asia Pacific Xiao Chen Phone: +44 (0) x.chen@horizondiscovery.com Jinghua Li Phone: +44 (0) j.li@horizondiscovery.com Shipping We ship direct to the USA, Canada, UK and parts of Europe and work closely with distributors in a number of countries to provide a service which is local to you and these can be seen below. For direct shipments we aim to ship your order direct within 5 business days and we will notify you of your expected delivery date. Territory Price (Room Temperature) Price (4 C) Service US & Canada $25.00 $45.00 FEDEX International Priority EU Countries FEDEX International Priority UK Royal Mail Recorded Signed For Rest of the World $ $80.00 $ $ FEDEX International Priority 30

31 Contact Your Local Distributor Horizon is committed to making HDx Reference Standards as widely available as possible. By working with Distribution Partners, we are able to offer products at a competitive price, with efficient logistics, and the advantages of local service. Horizon Diagnostics has established partnerships with the following distributors: Territory Distributor Phone/Fax Australia (Free Call) admin@metagene.com.au Belgium, France, Luxembourg 33 (0) (Tel) 33 (0) (Fax) contact@amplitech.net Czech Republic, Slovakia Czech Republic +420 (24) (Tel) info@bioconsult.cz Slovakia +421 (02) (Tel) 6 info@bioconsult.skk Hong Kong -- joanne@onwon.com.hkk Israel -- aline@prontodiagnostics.com Italy Japan -- Davide.DeLuca@ diatechpharmacogenetics.com -- hdx@rikengenesis.jp Netherlands +31 (0) (Tel) +31 (0) (Fax) info@bioke.com Poland +48 (71) (Tel) +48 (71) (Fax) info@syngen.pl zamowienia@syngen.pl Scandinavia Denmark (Tel) (Fax) Claus.Larsen@electrabox.com Finland Norway (Tel) (Fax) (Tel) (Fax) Jussi.Kontturi@electrabox.com Marika.Naukkarinen@electrabox. com Andrey.Sokolov@electrabox.com Sweden (Tel) (Fax) Tony.Bjoern@electrabox.com Lisa.Gustafsson@electrabox.com South Korea -- biomed@abionbio.com Spain (Tel) (Fax) info@durviz.com Identify and Control Variability Every Day 31

32 How to to Order Order Online Our online catalog and ordering system can be used to search our full menu of available reference standards. Select your desired reference standards and add them to the shopping basket. Your order can be submitted instantly using credit card, telephone ordering or a purchase order number as the preferred payment method. We accept the following cards: Please view our full terms and conditions online: Offline If you prefer to send us orders outside our online ordering system, please use the contact details below for telephone, fax, and ordering. To order offline we will require the following information: Product code(s) of the item(s) you wish to order (e.g. HD123 ) Your name, address, title and organization Shipping address and billing address with contact names Purchase Order number if you have one Telephone number VAT Number (European Countries only) For general enquiries: info@horizondiscovery.com (Information) orders@horizondiscovery.com (Orders) technical@horizondiscovery.com (Technical) Telephone UK +44 (0) US (East Coast) +1 (800) US (West Coast) +1 (800) Fax UK +44 (0) USA +1 (800) Horizon Discovery 7100 Cambridge Research Park, Waterbeach, Cambridge, CB25 9TL, United Kingdom