The world leader in serving science Andy Felton Ph.D. Vice President Marketing & Product Management Clinical Sequencing Division Personalized Medicine Research Solutions

Overview Platforms Ion AmpliSeq™ & Oncomine™ Assays for Oncology Research New FFPE Direct Reagent Liquid Biopsy Solutions In Development – Immune Response Assays

Platforms

THE ONCOMINE ™ KNOWLEDGEBASE Pre-NGS sample prep: Custom / pre-designed panels Hundreds of gene variants per sample in single run Low input amounts Ion AmpliSeq ™ Technology* One of the world’s largest curated cancer genomic database: Public sources Peer reviewed literature Published clinical research trials * Compendia Bioinformatics *For Research Use Only. Not for use in diagnostic procedures. Ion Torrent ™ NGS platform: Minimal sample input Fast turnaround times Enables reproducible results Enables accurate performance All in a single run Ion Torrent™ Systems* Ion Torrent NGS Cancer Research Tools * Clinical research trials are not referring to any of the products presented in these slides.

Bladder Breast Colorectal Endometrial Esophageal Gastric GIST Glioblastoma Head and Neck Kidney Liver Melanoma Mesothelioma NSCLC Osteosarcoma Ovarian Pancreas Prostate Basal Cell SCLC Sarcoma Testicular Thyroid Solid Tumor Driver Variant Map Copy gainCopy lossHotspotDeleteriousGene fusion Legend: 0.01>0.30 Gene variants

Oncomine™ Focus Assay Categorized by somatic alteration type Hotspot genes Focal CNV gains Fusion drivers Intelligent design includes hotspot SNV and indels, CNVs and gene fusions 52 genes Categorized by potential relevance Labels Guidelines Drug Targets Clinical Trials >400(US) *For Research Use Only. Not for use in diagnostic procedures.

Oncomine Comprehensive Assay* *For Research Use Only. Not for use in diagnostic procedures. Categorized by somatic alteration type Hotspot genes Focal CNV gains Full CDS for DEL mutations & CNV loss Fusion drivers 143 genes: Several used in multiple applications (hotspot, CNV, driver fusion) 143 genes Categorized by potential relevance >450(US) Labels Guidelines Drug Targets Clinical Trials

Oncomine Knowledgebase Reporter: Variant Summary Table For Research Use Only. Not for use in diagnostic procedures.

Goals 1 Mickey Williams, PhD, Frederick National Laboratory for Cancer Research Phase I technical results – June patients enrolled for screening in the first 3 months -739 core needle biopsies sequenced with 87% success rate 9.5% of the 13% which were not sequenced had no tumor present at all, giving an effective 97.5 % success rate Optional fine needle aspirates, 97% of the samples were successfully sequenced - mandatory in Phase II providing a projected 98.6% success rate based on Phase I analysis National Cancer Institute-Molecular Analysis for Therapy Choice (MATCH)

Expanding Menu of Panels and Assays for Cancer Research Oncomine™ Focus Assay Oncomine™ Focus Assay Oncomine™ Comprehensive Assay Oncomine™ Comprehensive Assay Ion AmpliSeq™ Panels Robust results with limited sample input & simple automatable workflows Pre-designed or Custom-design options Primer pools only Cancer Hotspot Panel v2 Comprehensive Cancer Panel Colon and Lung Research Panel v2 50 Genes400 Genes22 Genes& Fusions BRCA1 and BRCA2 Panel RNA Fusion Research Panel TP53 Panel > 70 fusion transcripts Complete coverage of coding exons and exon-intron boundaries Exons and UTRs AML Panel 21 Genes White Glove Custom Panels Oncomine™ Assays Informed by the Oncomine™ Knowledgebase Single workflow for DNA and RNA Complete solution containing Primer Pools plus Library, Templating and Sequencing kits For Research Use only. Not for use in diagnostic procedures.

Our Vision for the Future: Oncomine Universal Dx Product One workflow to deliver results across many biomarkers enabled by targeted NGS One Test – all answers for patient stratification to available targeted therapies Solid tumor sample Oncomine ™ IVD Assay Sample reportPhysician-patient treatment decision Oncomine ™ Focus Assay * RUO Early Development Oncomine ™ Universal Dx Test* IUO Registration Trials Oncomine ™ Universal Dx Test* IVD Companion Diagnostics The content provided herein may relate to products that have not been officially released and is subject to change without notice. “For investigational use only. The performance characteristics of this product have not been established."

New solutions for FFPE sample handling

Introducing Ion AmpliSeq Direct FFPE DNA Protocol For Research Use Only. Not for use in diagnostic procedures. Demonstration video: Fast and easy one-tube, two-step protocol using Direct Reagent that eliminates the requirement for deparaffinization and purification DNA is prepared in 30 min with only 10 min hands-on time DNA lysate can either be quantified or used directly for Ion AmpliSeq targeted sequencing

Excellent Coverage Uniformity Across Challenging Sample Types Performance of Ion AmpliSeq high-content gene panel* across different tissues and varied amounts of input Ion AmpliSeq Direct FFPE DNA lysate (2-75 ng) *134 gene targets 2,530 primer pairs Uniformity of base coverage >95% For Research Use Only. Not for use in diagnostic procedures. 1 cm cm 2 DNA yield measured using Invitrogen TM Qubit TM 3.0 Fluorometer and Qubit ds HS Assay Kit.

Peripheral Monitoring

Breast and Colon panels in late stage development New Oncomine Lung cell free DNA assay New library method for targeted sequencing of key variants from single tube of banked blood research sample Increased sensitivity to detect rare variants present down to 0.1% in cfDNA Covering key hotspot mutations in 11 genes 157 Cosmic Hotspots New library method for targeted sequencing of key variants from single tube of banked blood research sample Increased sensitivity to detect rare variants present down to 0.1% in cfDNA Covering key hotspot mutations in 11 genes 157 Cosmic Hotspots ALK BRAF EGFR ERBB2 KRAS MAP2K1 MET NRAS PIK3CA ROS1 TP53 For Research Use only. Not for use in diagnostic procedures. Gene List T790M Included

Variant calls from FFPE vs Plasma (late stage lung cancer) SamplesVariantFFPEPlasma 1EGFR-L858R71.42%2.62% 2TP53-R158L51.89%4.32% 3MET-T1010I KRAS-G12C 43.87% 34.62% 51.75% 0.28% 4N/ANo detection 5EGFR-L858R MET-T1010I TP53-Y220C 58.44% 41.93% 35.54% 7.28% 48.72% 1.93% 6TP53-R158L10.19%1.26%

One sample ctDNA and CTC protocols NGS on one chip Analysis Circulating Tumor Cell & Cell Free DNA Analysis with Cynvenio Liquid Biopsy Immunomagnetic capture of CTC’s from single blood research tube enables CTC analysis without whole genome amplification as well as cfDNA and germline comparison Circulating tumor DNA (ctDNA) isolation Circulating tumour cells (CTCs) enrichment via the Cynvenio CTC Platform NGS sequencing assays for both CTC DNA and ctDNA analysis Unique workflows to get results from both ctDNA and CTCs from one sample, in one analysis For Research Use only. Not for use in diagnostic procedures.

Immuno-Oncology

Immuno-Oncology Field Expanding Rapidly Seizing the future in oncology (2015) >500 Immuno-Oncology clinical trials registered For Research Use only. Not for use in diagnostic procedures.

In Development 400 gene AmpliSeq Gene Expression Assay* Enables Accurate Stratification Oncomine™ Knowledgebase Clinical researchers from leading cancer centers and academic medical centers Large data sources Expert content selection Key Opinion Leaders Primary Literature ≥ 200 Publications Robust panel design strategy to enable a unique molecular signature development Immuno-oncology panel segregates high TIL tumor samples For Research Use only. Not for use in diagnostic procedures. *The content provided herein may relate to products that have not been officially released and is subject to change without notice.

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