The linking of specific cancer genetic alterations to molecular targeted therapies is driving a new era of personalised medicine

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2 The linking of specific cancer genetic alterations to molecular targeted therapies is driving a new era of personalised medicine Oncologica addresses this new era of precision medicine by exploiting state of the art molecular profiling enabling a patient s tumour to be matched directly with the most appropriate molecular targeted therapy. Oncologica s semiconductor profiling technology reduces the number of tests required for comprehensive tumour analysis, delivers faster results and at a much lower cost.

3 4 5 THE FIRST LABORATORY IN EUROPE TO OFFER THE ONCOMINE FOCUS ASSAY FOR PERSONALISED ONCOLOGY NEXT GENERATION SEQUENCING (NGS) TECHNOLOGY Our scientists and clinicians utilise state-of-theart next generation semiconductor sequencing technology (NGS) to rapidly detect actionable mutations in patients tumour samples to precisely match these alterations with new generation targeted therapies. Our targeted next generation sequencing assay enables simultaneous detection of thousands of genetic variants across 52 genes relevant to solid tumours. Targeted actionable hotspots include SNVs, indels, CNVs and gene fusions. Oncologica carries out DNA sequencing of patients tumour samples using semiconductor chip technology directly translating chemically encoded information (A, C, G, T) into digital information. Semiconductor sequencing has major advantages over other sequencing technologies because it can be used to sequence low DNA/RNA input FFPE biopsy samples with high throughput and at a reduced cost. The Oncofocus Assay, a targeted sequencing platform, is designed to detect actionable mutations in cancer genes targeted by onmarket oncology drugs or treatments in Analysis of the output from the Oncofocus assay is performed using the Oncomine Knowledgebase Reporter, an analytical system used to identify and prioritise potential Nucleotides flow sequentially over an Ion semiconductor chip One sensor per well per sequencing reaction Direct detection of natural DNA extension Millions of sequencing reactions per chip Fast cycle time, real time detection clinical trials. Intelligent design is driven by treatment strategies. The knowledgebase the Oncomine Knowledgebase, the world s largest curated compendium of cancer reporter enables Oncofocus detected variants to be linked to over 270 targeted therapies Ion semiconductor chip genomic information, including content aligned to approved therapies, current dntp practice guidelines and open clinical trials. H + C NGS T G A sensing layer sensor plate bulk drain source silicon substrate To column receiver Rothberg J.M. et al Nature doi:10/1038/nature10242 DNA Ions Sequence

4 6 7 Comprehensive analysis of major cancer driver genes in one single workflow dramatically reducing the cost of molecular profiling and accelerating reporting times Reduced number of tests that cancer patients require NGS semiconductor platform uses low DNA/RNA input (10ng) from FFPE samples enabling detection of actionable variants in fine needle biopsies and core needle aspirates Generates a comprehensive picture of actionable mutations providing the clinician with a detailed molecular blueprint for optimal therapy choices and improved patient outcomes Prevent the unwarranted prescribing of expensive targeted therapies to patients unlikely to benefit from such treatments Delivering New Generation Molecular Profiling for cancer targeted therapies to optimize treatment efficacy Identification of specific mutations known to be associated with response or resistance to targeted therapies Identification of new driver mutations following relapse allowing a switch to additional more appropriate targeted therapies Identification of driver mutations and linked therapies in rare tumour types for which treatment protocols are limited Molecular profiling conducted on routine diagnostic histological samples (formalin fixed paraffin embedded specimens) and liquid biopsies including circulating tumour DNA and circulating tumour cells (ctdna and CTCs)

5 8 9 TARGETED NGS FOR ALL SOLID TUMOUR TYPES TARGETED TREATMENTS The fully integrated Oncomine Focus Assay and linked Oncomine TM Knowledgebase Reporter informatics pipeline provides unparalleled information regarding an individual s tumour that can be exploited to optimise treatment selection using the new generation of molecular targeted agents. TUMOUR TYPE GENETIC VARIANTS TARGETED THERAPIES 35 genes and hundreds of variants tested in this tumour type Over 110 potential treatments in this tumour type KIT FUSION ROS1 FUSION Breast Bladder Colorectal Kidney Oesophagus Glioblastoma Head and Neck EGFR MUTATION NTRK2 MUTATION FGFR3 FUSION PIK3CA AMPLIFICATION NTRK3 MUTATION CABOZANTINIB AFATINIB VORINOSTAT DASATINIB MELANOMA Endometrial Mesothelioma Non Small Cell Lung Cancer Ovarian Gastric Osteosarcoma Pancreatic Liver Skin Soft Tissue Sarcoma Testicular Prostate Small Cell Lung Cancer PDGFRA MUTATION EGFR MUTATION BRAF MUTATION NTRK2 FUSION SMO MUTATION ERBB2 AMPLIFICATION ALK FUSION ERBB2 AMPLIFICATION RET MUTATION BRAF MUTATION IMATINIB MESYLATE CLR-457 CRIZOTINIB VEMURAFENIB EVEROLIMUS COBIMETINIB + RG-7446 DABRAFENIB CERITINIB + CHEMOTHERAPY GIST Thyroid PDGFRA AMPLIFICATION KIT MUTATION AFATINIB TRASTUZUMAB NERATINIB CETUXIMAB ERBB2 AMPLIFICATION FGFR4 MUTATION CDKN2A MUTATION PANITUMUMAB

6 10 11 TARGETED NGS FOR ALL SOLID TUMOUR TYPES TARGETED TREATMENTS The fully integrated Oncomine Focus Assay and linked Oncomine TM Knowledgebase Reporter informatics pipeline provides unparalleled information regarding an individual s tumour that can be exploited to optimise treatment selection using the new generation of molecular targeted agents. TUMOUR TYPE GENETIC VARIANTS TARGETED THERAPIES CDK4 MUTATION 35 genes and hundreds of variants tested in this tumour type Over 90 potential treatments in this tumour type Bladder Colorectal Kidney Glioblastoma FGFR2 AMPLIFICATION BRAF MUTATION ERBB2 AMPLIFICATION ERLOTINIB NERATINIB VEMURAFENIB Endometrial Breast Oesophagus Gastric Liver Skin Head and Neck Prostate PROSTATE PDGFRA MUTATION EGFR FUSION AXL FUSION AXL FUSION EGFR AMPLIFICATION ABL1 ABERRATION CDK4 MUTATION FGFR2 FUSION RET MUTATION AFATINIB IPILIMUMAB IMATINIB MESYLATE CRIZOTINIB + DASATINIB Mesothelioma Non Small Cell Lung Cancer Ovarian Osteosarcoma Pancreatic Soft Tissue Sarcoma Testicular Small Cell Lung Cancer AKL FUSION NTRK2 FUSION SMO MUTATION MAP2K1 MUTATION HRAS MUTATION ALK FUSION EGFR MUTATION DABRAFENIB + TRAMETINIB RIBOCICLIB JNJ CLR-457 DABRAFENIB CETUXIMAB GIST Thyroid TSC2 MUTATION MET FUSION PTCH1 MUTATION NTRK3 MUTATION CERITINIB MGCD-265 VORINOSTAT JNJ CABOZANTINIB

7 12 13 TARGETED NGS FOR ALL SOLID TUMOUR TYPES TARGETED TREATMENTS The fully integrated Oncomine Focus Assay and linked Oncomine TM Knowledgebase Reporter informatics pipeline provides unparalleled information regarding an individual s tumour that can be exploited to optimise treatment selection using the new generation of molecular targeted agents. TUMOUR TYPE GENETIC VARIANTS TARGETED THERAPIES 12 genes and hundreds of variants tested in this tumour type Over 30 potential treatments in this tumour type Bladder Colorectal Kidney Glioblastoma ALK FUSION EGFR MUTATION KIT MUTATION RET FUSION RET MUTATION GEFITINIB VEMURAFENIB Endometrial Breast Mesothelioma LUNG Oesophagus Gastric Osteosarcoma Liver Skin Soft Tissue Sarcoma Head and Neck Prostate Small Cell Lung Cancer ERBB2 MUTATION KRAS MUTATION MET AMPLIFICATION EGFR MUTATION CDK4 MUTATION EGFR MUTATION KRAS G12 MUTATION HRAS MUTATION ALK FUSION PTCH1 MUTATION DASATINIB CABOZANTINIB CRIZOTINIB CETUXIMAB* NIVOLUMAB IMATINIB MESYLATE CLR-457 AZD-9291 PALBOCICLIB Ovarian Pancreatic Testicular PDGFRA MUTATION TSC2 MUTATION MET FUSION ERLOTINIB DABRAFENIB AFATINIB GIST Thyroid PDGFRA MUTATION CRIZOTINIB TRASTUZUMAB + CAPECITABINE MET AMPLIFICATION BRAF MUTATION ERBB2 AMPLIFICATION DASATINIB *contraindicate

8 14 15 ONCOFOCUS PATIENT TEST REPORT PUBLISHED THERAPIES SUMMARY In this cancer type In other cancer type In this cancer type and other cancer types Contraindicated No evidence available (IV), (III), (II/III), (II), (I/II), (I) Clinical trial phase Published therapy Current FDA information NCCN Guidelines Open clinical trials for this cancer type* Oncomine Cancer Panel Patient Test Report SUBJECT INFORMATION Pre-Screening Subject No.: Subject Initials: (first/middle/last) Date of Birth: (dd/mmm/yyyy) Life Technologies Clinical Services Lab 910 Riverside Parkway, Suite 60 West Sacramento, CA Ph: (888) Fax: (855) lifelabdx.com SITE INFORMATION Investigator Name: Site ID: Date of Shipment: (dd/mmm/yyyy) Gender: M F Phone: Fax: SPECIMEN INFORMATION cetuximab panitumumab panitumumab + chemotherapy (II) regorafenib + FOLFIRI (II) sorafenib + cetuximab (II) Accession No.: Date Specimen Received: Date Reported: TEST RESULTS In this cancer type In other cancer type In this cancer type and other cancer types Mutations Amino Acid Current FDA Gene Geneotype Classification Change Information Contraindicated No evidence available Number of therapies with NCCN clinical trials in this Guideline therapies KRAS p.ala146thr c.436g>a Gain of Function 2 15 KIT p.met541leu c.1612a>c Gain of Function 1 1 MET p.asn375ser c.1124a>g Gain of Function 3 TP53 p.arg234cys c.700c>t Loss of Function 1 TP53 p.pro33arg c.98c>g Loss of Function 1 PUBLISHED THERAPIES DETAIL - NCCN GUIDELINES NCCN Guidelines information is current as of For the most up-to-date information, go to Copy Number Variations Current FDA NCCN Number of therapies with Gene Type Classification Information Guideline clinical trials in this therapies PTEN Deletion Loss of Function 5 There is no current FDA information, NCCN guidelines, or open clinical trials for the following detected copy number variations: RPS6KB1 Amplification, FLT3 Amplification, ACVRL1 Amplification, PTCH1 Deletion, CDKN2A Deletion, MYC Amplification, TERT Amplification, TET2 Deletion, VHL Deletion. Read the Full Report on Other mutations, copy number variations, or fusions of that were detected but not classified by the Oncomine Knowledgebase as a genetic driver of cancer are not listed in the results section of this report. All other genes listed in the Test Description that do not appear in the results section either did not have a detected variant or the variant is not classified as a genetic driver for cancer. Laboratory director: John E. Glassco, MD, FCAP CLIA number: 05D Life Technologies Clinical Services Lab tests are intended for clinical use. They were developed and their performance characteristics determined by the Life Technologies Clinical Services Lab, which is certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) to perform high complexity testing. The tests have not been cleared or approved by the United States Food and Drug Administration; however, such clearance or approval is not currently required Life Technologies Corporation. All rights reserved. The trademarks mentioned herein are the property of Life Technologies Corporation and/or its affiliate(s). cetuximab Cancer type: Colorectal Cancer Class: KRAS mutation Contraindication: Based upon lower-level evidence, there is uniform NCCN consensus (Category 2A) that patients with any known KRAS or NRAS mutation should not be treated with either cetuximab or pantitumumab. (COL-A 4 of 5, MS-34) Reference: NCCN Guideline Version Colon Cancer TEST RESULTS SUMMARY PUBLISHED THERAPIES DETAIL - OPEN CLINICAL TRIALS Mutations Gene In this cancer type In other cancer type In this cancer type and other cancer types Amino Acid Change Geneotype Classification Current FDA Information Contraindicated NCCN Guideline No evidence available Number of therapies with clinical trials in this therapies KRAS p.ala146thr c.436g>a Gain of Function 2 15 KIT p.met541leu c.1612a>c Gain of Function 1 1 MET p.asn375ser c.1124a>g Gain of Function 3 TP53 p.arg234cys c.700c>t Loss of Function 1 NCT : A Phase I Trial of Irinotecan and BKM120 in Previously Treated Advanced Colorectal Cancer Class: KRAS mutation Population segment(s): Second line or greater/refractory/relapsed, Stage III, Stage IV Phase: I Published therapy: buparlisib + irinotecan Location(s): KS Contact: Stacey Purinton [ ;spurinton@kumc.edu]

9 LONGITUDINAL DYNAMIC MONITORING OF PATIENTS RECEIVING TARGETED THERAPIES SERVICE FLOW PROFILING FLOW EXAMPLE DNA+RNA extraction Sample receipt FFPE block, curl or liquid biopsy ONCOFOCUS PATIENT TEST REPORT Primary diagnosis Relapse Liquid biopsy e.g. ctdna, CTCs Construct Library ACTIONABLE DIAGNOSIS Initial profiling e.g EGFR L858R mutation Secondary profiling, e.g. EGFR T790M resistance mutation Prepare template Template enrichment DRUG RESPONSIVENESS ANALYSIS Routine histological samples Run sequence CLINICAL TRIALS INFORMATION Candidate treatment: erlotinib,gefitinib, afatinib,dacomitinib neratinib Candidate treatment: AZD-9291 Data Analysis Report generation AVERAGE TURNAROUND TIME: 10 DAYS Return of hard copy and sample Secure electronic transfer of report

10 18 19 EXAMPLES OF GENETIC VARIANTS AND TARGETED TREATMENTS Alteration Tumour type Example treatment(s) ALK fusion NSCLC ceritinib, crizotinib AKT1 mutation Multi cancer MK-2206, MSC A *BAP1 mutation Melanoma vorinostat BRAF mutation Melanoma dabrafenib, trametinib, vemurafenib BRAF mutation NSCLC dabrafenib, vemurafenib BRCA1 mutation, deletion Multi cancer rucaparib, veliparib BRCA2 mutation, deletion Multi cancer rucaparib, veliparib CCND1 amplification Multi cancer palbociclib CDK4 amplification, mutation Melanoma, NSCLC palbociclib CDK6 amplification NSCLC palbociclib *CDKN2A mutation Multi cancer crizotinib + dasatinib, palbociclib DDR2 mutation Multi cancer crizotinib + dasatinib EGFR mutation NSCLC afatinib, erlotinib ERBB2 amplification Breast cancer pertuzumab, trastuzumab ERBB2 amplification Gastric cancer trastuzumab ERBB2 amplification NSCLC afatinib ERBB3 mutation Multi cancer neratinib FGFR1-4 mutation, amplification, fusion Multi cancer GNA11 mutation Melanoma vorinostat GNAQ mutation Melanoma vorinostat BGJ-398, JNJ HRAS mutation Multi cancer binimetinib + panitumumab, BVD-523 *available soon Alteration Tumour type Example treatment(s) IDH1 mutation Multi cancer AG-120 KIT amplification Melanoma dasatinib KIT mutation Melanoma imatinib mesylate KIT mutation GIST imatinib, sunitinib, regorafenib KRAS mutation Colorectal cancer cetuximab, panitumumab contraindicated KRAS mutation Multi cancer various MEKi combinations MET amplification NSCLC crizotinib MET mutation Multi cancer AMG-337, crizotinib, INCB MTOR mutation Multi cancer MSC A MYCN amplification Multi cancer GSK NRAS mutation Colorectal cancer cetuzimab, panitumumab contraindicated NRAS mutation Multi cancer various MEKi combinations PDGFRA amplification Glioblastoma nilotinib, sorafenib PDGFRA mutation GIST dasatinib PIK3CA mutation Multi cancer various PI3K pathway combinations PPARG fusion Thyroid cancer pioglitazone *PTCH1 mutation Multi cancer vismodegib PTEN deletion, mutation Multi cancer various PI3K pathway combinations RET fusion NSCLC cabozantinib RET mutation NSCLC, Thyroid cancer ponatinib, sunitinib ROS1 fusion NSCLC crizotinib SMO mutation Multi cancer vismodegib STK11 mutation Multi cancer MSC A TP53 mutation Multi cancer MK-1775, MK-8242 *TSC1,2 m utation Multi cancer MSC A Approved - FDA labels Approved - NCCN Investigational - Trials

11 20 ONCOLOGICA TEST MENU FOR PERSONALISED ONCOLOGY ONCOFOCUS PANEL 52 GENE LIST SUMMARY Oncofocus Test Comprehensive NGS targeted panel for precision therapy Oncofocus was developed as part of the US NCI-MATCH (Molecular Analysis for Therapy Choice) program for precision oncology involving 2400 NCI-affiliated hospitals, >700,000 patients samples, 120 phase 3 and 215 early phase trials. The Oncofocus test utilises state of the art semiconductor technology to rapidly sequence DNA/ RNA extracted from routine FFPE surgical biopsy material. The assay is designed to detect thousands of genetic alterations including SNPs, indels, CNVs and fusions across 52 of the major cancer driver genes linked to solid tumours. The data generated by the Oncofocus test is analysed using the Oncomine Knowledgebase informatics pipeline, the world s largest curated compendium of cancer genetic information, enabling genetic alterations/variants to be linked to over 280 targeted therapies. Targeted therapies include all classes: -FDA approved therapies, -national comprehensive cancer network (NCCN) guideline referenced therapies and -therapies entered into US, EU and Japanese phase I, II and III clinical trials. 52 Genes relevant to solid tumors to detection of thousands of variants gene alterations aligned 21 over HOTSPOT GENES AKT1 ALK AR BRAF CDK4 CTNNB1 DDR2 EGFR ERBB2 ERBB3 ERBB4 ESR1 FGFR2 23 FUSION DRIVERS COPY NUMBER VARIANTS FGFR3 GNA11 GNAQ HRAS IDH1 IDH2 JAK1 JAK2 JAK3 KIT KRAS MAP2K1 MAP2K2 MET MTOR NRAS PDGFRA PIK3CA RAF1 RET ROS1 SMO ALK AR BRAF CCND1 CDK4 CDK6 EGFR ERBB2 FGFR1 FGFR2 FGFR3 FGFR4 KIT KRAS MET MYC MYCN PDGFRA PIK3CA ABL1 AKT3 ALK AXL BRAF EGFR ERBB2 ERG ETV1 ETV4 ETV5 FGFR1 FGFR2 FGFR3 MET NTRK1 NTRK2 NTRK3 PDGFRA PPARG RAF1 RET ROS1 targeted therapies and many more undergoing clinical trials CNV FUSION HOTSPOT HOTSPOT + FUSION HOTSPOT + CNV Additional tests for targeted therapies available. Please visit CNV + FUSION HOTSPOT + CNV + FUSION

12 22 MANAGEMENT TEAM Professor Gareth Williams and Dr Marco Loddo are Co-founders and Directors of Oncologica and have in-depth knowledge and expertise in diagnostic oncopathology, translational biology, biomarker discovery and drug development. Kitty Williams is the Senior Commercial Manager and is responsible for providing advice and implementation on commercial and corporate matters Philippa Jones is the Senior Operations Manager and directs the tissue based diagnostic services of the company. Katherine Marquis is the Senior Biomedical Scientist who directs the precision oncology services for targeted therapies TELEPHONE MAIL Keeda-Marie Snelson is the Lead Clinical Scientist with extensive expertise in the analysis of cancer genetic variants of clinical prognostic and predictive significance. Rebecca Cadman is the Business Development Manager and is responsible for exploring new market opportunities and providing comprehensive support for existing clients. Read more about our team by visitng Suite The Science Village, Chesterford Research Park, Chesterford, Cambridge, CB10 1XL

13 Suite The Science Village, Chesterford Research Park, Chesterford, Cambridge, CB10 1XL