Introducing VarSeq Dx as a Medical Device in the European Union

A transition period regarding in vitro medical device (IVD) regulation in the European Union (EU) is upon us. The former IVDD regulations are phasing out and IVDR 2017/746 has already taken its place as the acting regulation for IVD manufacturers but also lab developed tests (LDTs) and health institutions. In our upcoming webcast we will talk about the roles and significance of IVDR and ISO 13485 certification for clinical labs and for Golden Helix as a medical device manufacturer.

Join us as we will introduce VarSeq 2.6.1 complete with Dx Mode, which offers the use of VarSeq as CE marked medical device. Even more we will also present strategies to facilitate the transition of Golden Helix customers to operate in accordance with IVDR.

1. May 22, 2024 Presented by Julia Love Introducing VarSeq Dx as a Medical Device in the European Union

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3. May 22, 2024 Presented by Julia Love Introducing VarSeq Dx as a Medical Device in the European Union

4. Today’s Presenter 4 Rana Smalling, PhD Gabe Rudy VP Product & Engineering Introducing VarSeq Dx as a Medical Device in the European Union Julia Love Associate Director of Product Quality

5. NIH Grant Funding Acknowledgments 5 Research reported in this publication was supported by the National Institute Of General Medical Sciences of the National Institutes of Health under: Award Number R43GM128485-01 Award Number R43GM128485-02 Award Number 2R44 GM125432-01 Award Number 2R44 GM125432-02 Montana SMIR/STTR Matching Funds Program Grant Agreement Number 19-51-RCSBIR-005 NIH SBIR Grant 1R43HG013456-01  PI is Dr. Andreas Scherer, CEO of Golden Helix. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

6. Golden Helix at-a-Glance 6 Company Snapshot: Leading SaaS provider of tertiary genomic analysis solutions for NGS labs Golden Helix is a SaaS bioinformatics solution provider specializing in next-gen sequencing (“NGS”) data analysis  The Company’s software enables automated workflows and variant analysis for gene panels, exomes, and whole genomes  Key Clinical Applications Prenatal testing Hereditary disease testing Reproductive testing Oncology Marquee Global Clients Golden Helix’s solutions allow clients to increase throughput, ensure consistent quality, maximize revenue, and save time  1998 Company Founded Bozeman, Montana Headquarters Recognitions Government Research Pharmaceuticals Agrigenomics Testing Labs Translational Labs Human Genetics Research Hospitals Academia Publications Content & Resources Pharmacogenetics testing

7. NGS Clinical Workflow Golden Helix provides comprehensive data analytics software that scales across gene panels, whole exomes, and whole genomes DNA Extraction in Wet Lab and Sequence Generation Interpretation and Result Reporting Primary Read Processing and Quality Filtering Alignment and Variant Calling Secondary *Golden Helix provides Secondary Analysis through a reseller agreement Tertiary Golden Helix’s software and primary focus Comprehensive secondary and tertiary analysis solutions for primary data aggregated by all commercially available sequencers Type Size Gene Panel Small (100MB) Whole Exome Medium (1GB) Whole Genome Large (100GB) Cancer use case Hereditary use case Process Analysis … and scales across multiple data set sizes for cancer and hereditary use cases Filtering and Annotation Data Warehousing Workflow Automation Golden Helix works with all major sequencers and testing kit providers…

8. NGS Clinical Workflow Golden Helix provides comprehensive data analytics software that scales across gene panels, whole exomes, and whole genomes DNA Extraction in Wet Lab and Sequence Generation VSClinical Primary Sentieon PLOT & UMI Sentieon DNAseq Secondary *Golden Helix provides Secondary Analysis through a reseller agreement Tertiary Golden Helix’s software and primary focus Comprehensive secondary and tertiary analysis solutions for primary data aggregated by all commercially available sequencers Type Size Gene Panel Small (100MB) Whole Exome Medium (1GB) Whole Genome Large (100GB) Cancer use case Hereditary use case Process Analysis … and scales across multiple data set sizes for cancer and hereditary use cases VarSeq VSWarehouse VSPipeline Golden Helix works with all major sequencers…

9. ISO Certification 13485:2016 9 ISO 13485:2016 from TÜV SÜD ISO 13485:2016 is an international standard that specifies requirements for a quality management system (QMS) for organizations involved in the design, development, production, and servicing of medical devices. maintain a quality management system demonstrate sufficient risk management show consistent tracking of customer satisfaction and safety in the market demonstrate continued improvement efforts on the product and system level.  ISO 13485:2016 is designed to objectively document that we are holding ourselves to the highest quality standards as we are providing innovative solutions to hospitals, testing labs, and research institutions globally.

10. In vitro Medical Device Regulation (IVDR) 10 The purpose of IVDR is to ensure consistency in safety and performance for in vitro diagnostic medical devices (IVDs). Lab developed tests may incorporate one or more IVDs Key incidents led to the need for stricter IVD regulation and IVDR was created Labs need to update their quality management system which is expected to be ISO 13485 compliant under IVDR.

11. IVDR Transition Timeline 11 2022 2030 2027 2028 2029 IVDR Valid All new devices must comply with IVDR IVDD Class D Devices IVDD certified devices must comply with IVDR IVDD Class A sterile and Class B Devices IVDD certified devices must comply with IVDR IVDD Class C Devices IVDD certified devices must comply with IVDR IVDD Invalid Sell-off period is complete

12. ISO 13485 for Labs and Health Institutions 12 Proof to customers that the organization follows high-quality standards ISO 15189 compliant labs should make changes to existing q uality management systems to comply with ISO 13485 Building based on IVDR compliant devices and ISO 13485 certified manufacturers simplifies LDT development 

13. Golden Helix So lution 13 Golden helix is an ISO 13485 device manufacturer as of January 2024 VarSeq is a CE marked Medical Device under IVDR as of April 2024  VarSeq is CE marked in version 2.6.1 when Dx Mode is activated

14. VarSeq Dx Mode Requirements 14 Reviewed Installation Verification Test (IVT) Confirmation that VarSeq was correctly installed Confirmation that standard VarSeq features function as expecte d 1 Golden Helix User Certification Program Tiered approach to certification based on licensed VarSeq features Declaration of proficiency certificate earned when certification program is completed 2

15. VarSeq DX Mode 15

16. VarSeq DX Mode 16

17. Summary of VarSeq as a Medical Device 17 It is essential for clinical labs in the EU to leverage IVDR-compliant devices and work with ISO 13485-certified manufacturers VarSeq 2.6.1 introduces VarSeq Dx Mode and will be offered for all future VarSeq releases To use VarSeq as a medical device customers need to confirm acceptable VarSeq installation and user certification.

18. NIH Grant Funding Acknowledgments 18 Research reported in this publication was supported by the National Institute Of General Medical Sciences of the National Institutes of Health under: Award Number R43GM128485-01 Award Number R43GM128485-02 Award Number 2R44 GM125432-01 Award Number 2R44 GM125432-02 Montana SMIR/STTR Matching Funds Program Grant Agreement Number 19-51-RCSBIR-005 NIH SBIR Grant 1R43HG013456-01  PI is Dr. Andreas Scherer, CEO of Golden Helix. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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20. eBook Library 20 Prenatal Genetics – Learn the Following Existing approaches to prenatal WES, along with clinical indications for its use   How VarSeq and VSClinical can be utilized for its use A few interesting cases of variants and their classifications Pharmacogenetics – Learn the Following Foundations of Pharmacogenomics Genetic variability and drug response Pharmacogenomic test reporting nomenclature and terminology The Pharmacogenomic eco-system VSPGx - A pharmacogenomics application

21. 21 Discover the Latest at Golden Helix's Booth at booth 428! In-Booth software demos. Famous t-shirts for demo attendees. EBooks , engaging discussions, and more!  Corporate Satellite Talk Golden Helix – A Clinical Interpretation Solution for Next Generation Sequencing Labs Monday, June 3rd, 12:00-13:00, Room: New York 1 Presented by:  Dr. Andreas Scherer, Golden Helix President & CEO Nathan Fortier, PhD, Golden Helix Director of Research Jennifer Dankoff, PhD, Field Application Scientist Guest Speakers: Tina Han, Director of Applications & Business Development, Twist BioSciences David Stucki, Field Application Support Manager, PacBio ESHG 2024: What to Expect Dr. Andreas Scherer Nathan Fortier Jennifer Dankoff Tina Han David Stucki

22. ESHG Booth #428 Demo Schedule 22 Saturday, June 1st Sunday, June 2nd Monday, June 3rd 10:10 - PGx: Pharmacogenomics Workflow 12:10 - VarSeq Dx: Using the VarSeq Suite as a Medical Device Under IVDR 12:40 - Whole Genome Analysis with Long Read Data 13:10 - Calling CNV with Twist Exome 2.0 13:30 - NGS Enterprise Capabilities - Automation, Warehousing, Continuous Improvement 16:10 - Carrier Status Analysis in VarSeq 18:10 - Somatic NGS Workflow with VarSeq - Streamlining Tertiary Analysis with Oncogenicity Classifier and CancerKB 10:10 - Somatic NGS Workflow with VarSeq - Streamlining Tertiary Analysis with Oncogenicity Classifier and CancerKB 12:10 - PGx: Pharmacogenomics Workflow 12:40 - VarSeq Dx: Using the VarSeq Suite as a Medical Device Under IVDR 13:10 - Whole Genome Analysis with Long Read Data 13:40 - Carrier Status Analysis in VarSeq 15:40 - NGS Enterprise Capabilities - Automation, Warehousing, Continuous Improvement 16:40 - Calling CNV with Twist Exome 2.0 10:10 - Carrier Status Analysis in VarSeq 12:00 - 13:00 Corporate Satellite Talk (Room: New York 1): Golden Helix: A Clinical Interpretation Solution for Next-Generation Sequencing 13:30 - VarSeq Dx: Using the VarSeq Suite as a Medical Device Under IVDR 15:40 - PGx: Pharmacogenomics Workflow 16:10 - Calling CNV with Twist Exome 2.0 16:40 - NGS Enterprise Capabilities - Automation, Warehousing, Continuous Improvement

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