StrandAdvantage Tissue-Specific Cancer Genomic Tests. Empowering Crucial First-Line Therapy Decisions for Your Patient

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1 StrandAdvantage Tissue-Specific Cancer Genomic Tests Empowering Crucial First-Line Therapy Decisions for Your Patient

2 Harness the power of precision medicine with StrandAdvantage Precision medicine in cancer refers to the delivery of personalized treatment based on the characteristics of the individual s tumor genetics, using targeted therapies that efficiently kill tumor cells. As advances in cancer research and drug development provide multiple treatment options, oncologists are faced with the challenging task of deciding which therapy works best for their patients. Delivering highly targeted, actionable treatment options based on the patients genetic profile, StrandAdvantage enables optimised decision making. StrandAdvantage matches actionable cancer genes in solid tumors to all relevant, FDA-approved and NCCN recommended cancer therapies, enabling timely decisions about effective personalized therapies for patients. Strand s NGS-based genomic profiling combined with validated molecular markers eliminates the need for multiple tests plus, provides a comprehensive view of therapy-relevant genomic and proteomic changes in an easy-to-read report.

3 StrandAdvantage: Lung Carcinoma Report StrandAdvantage provides targeted, actionable, standard-of-care treatment options in days instead of weeks Easy-to-read report highlights the genomic alterations, and summarizes available treatment options for your patient by recommending appropriate therapies, approved by FDA or recommended by NCCN for the cancer tissue type. Strand Center for Genomics and Personalized Medicine (A unit of Strand Life Sciences Pvt. Ltd.) UAS Alumni Association Building, Veterinary College Campus, Bellary Road, Bangalore , support.strandx@strandls.com, Patient XXXXXXXXX TRF ID SOMATIC-XX Test StrandAdvantage Test Gender Female Block ID XXXXXX Type SOC Report Age 75 years Specimen Type FFPE Block Date Collected 06/10/15 MRN NA Specimen Site Lung Date Received 10/10/15 Clinician XXXXXXXXX Date Generated 21/10/15 Hospital XXXXXXXXX Clinical Indications Lung adenocarcinoma Summary for Standard Drugs The patient does not meet the inclusion criteria for Ceritinib, Crizotinib, Vemurafenib, Dabrafenib and Trastuzumab based on the results of this test. Therapy Relevant Marker Tested Markers Predicted Response** Gefitinib EGFR + EGFR, KRAS, ERBB2, MET Erlotinib EGFR + EGFR, KRAS, ERBB2, MET Afatinib EGFR + EGFR, KRAS, ERBB2, MET Bevacizumab -- KRAS, VHL Markers for Vinorelbine, Carboplatin, Paclitaxel, Topotecan, Docetaxel, Mitomycin, Cisplatin, Doxorubicin, Etoposide, Cabozantinib, Ifosfamide, Pemetrexed, Irinotecan, Mechlorethamine, Methotrexate, Gemcitabine, Nivolumab, Ramucirumab, Vinblastine are not part of the StrandAdvantage SOC Report. Enhanced Response - Better than standard population response due to the presence or absence of specific markers. Enhanced but Limited Response - Better than standard population response mitigated by the presence of conflicting markers. Standard Response - Expected response similar to the typical population response for the specific therapy. Poor response - Likely poorer response or increased toxicity than the standard population response due to the presence of specific markers. ** Clinical Correlation Recommended Report shown for representative purposes only.

4 Overview of StrandAdvantage Non-Small Cell Lung Carcinoma (NSCLC) Test The Test The StrandAdvantage Non-Small Cell Lung Carcinoma (NSCLC) test comprehensively maps actionable mutations in the tumor and matches them to appropriate FDA approved/nccn recommended therapy regimens. The test detects low-frequency sequence variations with high sensitivity and specificity from a single biopsy sample. FDA Approved and NCCN Recommended Therapies Impacted by Genetic Markers Erlotinib, Gefitinib Afatinib Osimertinib Crizotinib Ceritinib EGFR, ERBB2, KRAS, MET EGFR, ERBB2, KRAS, MET EGFR ALK* ALK* Bevacizumab Vemurafenib Dabrafenib Trastuzumab KRAS, VHL BRAF BRAF EGFR, ERBB2, MET, PIK3CA Alectinib ALK* * Measured by FISH Erlotinib, Gefitinib, Afatinib: Most EGFR alterations indicate response to erlotinib, gefitinib and afatinib, while some mutations indicate resistance to them. Alterations in MET or KRAS may indicate poor response to erlotinib, gefitinib and afatinib. Alterations in ERBB2 indicates poor response to erlotinib and gefitinib but possible response to afatinib. Osimertinib: Tumors with EGFR T790M mutation may respond to osimertinib. Trastuzumab: Alterations in ERBB2 are associated with response to trastuzumab while mutations in EGFR, MET or PIK3CA are associated with poor response. Bevacizumab: Mutations in KRAS may indicate limited response to bevacizumab while alterations in VHL indicates possible response. Crizotinib, Ceritinib, Alectinib: ALK rearrangement indicates response to crizotinib, ceritinib, and alectinib. Alterations in MET and ROS1 rearrangement may indicate response to crizotinib. Vemurafenib, Dabrafenib: Mutations in BRAF indicate possible response to vemurafenib and dabrafenib.

5 StrandAdvantage: Breast Carcinoma Report StrandAdvantage provides targeted, actionable, standard-of-care -care treatment options in days instead of weeks Easy-to-read report highlights the genomic alterations, and summarizes available able treatment options for your patient by recommending appropriate propriate therapies, approved by FDA or recommended by NCCN for the cancer tissue type. Strand Center for Genomics and Personalized Medicine (A unit of Strand Life Sciences Pvt. Ltd.) UAS Alumni Association Building, Veterinary College Campus, Bellary Road, Bangalore , support.strandx@strandls.com, Patient STRAN-xxx TRF ID SOMATIC-xx Test StrandAdvantage Test Gender Female Block ID XXXXXX Type SOC Report Age Not Available Specimen Type FFPE DNA Sample Collected 08/10/15 MRN NA Specimen Site Breast Sample Received 11/10/15 Clinician XXXXXXXXXX Report Generated 22/10/15 Hospital XXXXXXXXXXX Clinical Indications Breast carcinoma (ER+ve/PR+ve/HER2-ve) Summary for Standard Drugs The patient does not meet the inclusion criteria for Lapatinib, Pertuzumab and Trastuzumab based on the results of this test. Therapy Relevant Marker Tested Markers Predicted Response** Epirubicin TOP2A IHC + PgP, TOP2A Doxorubicin TOP2A IHC + PgP, TOP2A Everolimus PTEN + HER2, ER, PIK3CA, PTEN Tamoxifen ER IHC + EGFR, HER2, ER, ERBB2 Bevacizumab -- VHL Palbociclib -- HER2, ER Docetaxel TUBB3 IHC + PgP, TUBB3 Paclitaxel TUBB3 IHC + PgP, TUBB3 Fluorouracil TS IHC + SMAD4, TS Report shown for representative purposes only. Markers for Exemestane, Toremifene, Carboplatin, Goserelin, Fulvestrant, Letrozole, Anastrozole, Capecitabine, Ixabepilone, Cisplatin, Cyclophosphamide, Megestrol, Methotrexate, Gemcitabine, Thiotepa, Vinblastine, Eribulin are not part of the StrandAdvantage SOC Report. se - Better than standard population response due to the presence or absence of specific markers. e - Better than standard population response mitigated by the presence of conflicting markers. imilar to the typical population response for the specific therapy. icity than the standard population response due to the presence of specific markers.

6 Overview of StrandAdvantage Breast Carcinoma Test The Test The StrandAdvantage Breast Carcinoma test comprehensively maps actionable mutations in the tumor and matches them to appropriate FDA approved/nccn recommended therapy regimens. The test detects low-frequency sequence variations with high sensitivity and specificity from a single biopsy sample. The test also includes IHC (immunohistochemistry) to assess the expression level and cellular localization of specific markers. These markers have been selected based on their therapeutic significance. FDA Approved and NCCN Recommended Therapies Impacted by Genetic Markers Everolimus Doxorubicin, Epirubicin 5-fluorouracil Bevacizumab * Indicates IHC markers ER*, HER2*, PIK3CA, PTEN* Pgp*, TOP2A* SMAD4, TS* VHL Lapatinib Trastuzumab Pertuzumab Paclitaxel, Docetaxel Tamoxifen ERBB2/HER2*, PIK3CA EGFR, ERBB2/HER2*, PIK3CA, PTEN EGFR, ERBB2/HER2*, PIK3CA, PTEN Pgp*, TUBB3* ER*, ERBB2/HER2*, EGFR Bevacizumab: Loss of VHL may indicate response to bevacizumab. 5-fluorouracil: Loss of SMAD4 and high levels of TS indicate poor response to 5-fluorouracil-based therapy, where as low levels of TS indicate response. Paclitaxel, Docetaxel: High levels of Pgp and TUBB3 indicate poor response to paclitaxel and docetaxel. Doxorubicin, Epirubicin: High levels of TOP2A indicate response to doxorubicin and epirubicin indicates response to doxorubicin and epirubicin. High levels of Pgp indicate poor response to doxorubicin and epirubicin. Trastuzumab, Pertuzumab, Lapatinib: Alterations in ERBB2 indicate response to anti-her2 therapy such as trastuzumab, pertuzumab and lapatinib. In HER2 positive breast cancers, mutation in PIK3CA, alterations in EGFR or low levels of PTEN indicate poor response to trastuzumab and pertuzumab. Everolimus: In ER positive, HER2 negative breast cancer, mutations in PIK3CA or loss of PTEN expression or function may indicate enhanced response to everolimus. Tamoxifen: In ER positive breast cancer, alterations in EGFR and ERBB2, and high levels of HER2 may indicate poor response to tamoxifen.

7 StrandAdvantage: Colorectal Carcinoma Report StrandAdvantage provides targeted, actionable, standard-of-care treatment options in days instead of weeks Easy-to-read report highlights the genomic alterations, and summarizes available treatment options for your patient by recommending appropriate therapies, approved by FDA or recommended by NCCN for the cancer tissue type. Strand Center for Genomics and Personalized Medicine (A unit of Strand Life Sciences Pvt. Ltd.) UAS Alumni Association Building, Veterinary College Campus, Bellary Road, Bangalore , support.strandx@strandls.com, Patient XXX TRF ID SOMATIC-XX Test StrandAdvantage Test Gender Male Block ID XXXXXX Type SOC Report Age 40 years Specimen Type FFPE Block Sample Collected 02/12/15 MRN NA Specimen Site Colon Sample Received 06/12/15 Clinician XXXXXX Report Generated 16/12/15 Hospital XXXXXX Clinical Indications Colorectal cancer Summary for Standard Drugs Therapy Relevant Marker Tested Markers Predicted Response** Oxaliplatin KRAS + KRAS Fluorouracil -- SMAD4, APC Bevacizumab KRAS + KRAS Panitumumab KRAS + EGFR, NRAS, KRAS, BRAF, MET, PIK3CA, PTEN PTEN Markers for Capecitabine, Ziv-Aflibercept, Irinotecan, Leucovorin, Regorafenib are not part of the StrandAdvantage SOC Report. Cetuximab KRAS + EGFR, NRAS, KRAS, BRAF, MET, PIK3CA, Enhanced Response - Better than standard population response due to the presence or absence of specific markers. Enhanced but Limited Response - Better than standard population response mitigated by the presence of conflicting markers. Standard Response - Expected response similar to the typical population response for the specific therapy. Poor response - Likely poorer response or increased toxicity than the standard population response due to the presence of specific markers. ** Clinical Correlation Recommended Report shown for representative purposes only.

8 Overview of Colorectal Carcinoma Test The Test The StrandAdvantage Colorectal Carcinoma test comprehensively maps actionable mutations in the tumor and matches them to appropriate FDA approved/nccn recommended therapy regimens. The test detects low-frequency sequence variations with high sensitivity and specificity from a single biopsy sample. FDA Approved and NCCN Recommended Therapies Impacted by Genetic Markers 5-fluorouracil Cetuximab Panitumumab Oxaliplatin Bevacizumab APC, SMAD4 BRAF, EGFR, KRAS, MET, NRAS, PIK3CA, PTEN BRAF, EGFR, KRAS, MET, NRAS, PIK3CA, PTEN KRAS KRAS Cetuximab, Panitumumab: Mutations in KRAS or NRAS indicate poor response to cetuximab and panitumumab while wild type status of these genes indicates favorable response. Additionally, alterations in BRAF, MET, PTEN or PIK3CA may indicate poor response. Alterations in EGFR may indicate favourable response to cetuximab and panitumumab in the absence of alterations in the above genes. Bevacizumab: Mutations in KRAS may indicate limited response to bevacizumab. 5-fluorouracil: Loss of APC and SMAD4 may indicate poor response to 5-fluorouracil. Oxaliplatin: Mutations in KRAS indicate possible response to oxaliplatin.

9 Why Strand StrandAdvantage offers oncologists and pathologists a powerful new tool to determine optimal therapeutic strategies for cancer patients and start treatments quickly. StrandAdvantage is designed for oncologists to use as a resource when making first-line decisions Standard-of-care gene profile results are delivered in ten working days. Comprehensive view of treatment options Strand s comprehensive database of genomic variants links to FDA-approved and NCCN recommended targeted cancer therapies. Best-in-class interpretation and reporting Expert Interpretation and reporting using proprietary technology with deep curation and interpretation conducted by a very large team of expert scientists. Easy-to-read reports. Chemotherapeutic Response StrandAdvantage provides information related to chemotherapeutic response for use in standard-of-care setting. StrandAdvantage provides extensively curated information from the literature on the genetic basis of chemotherapy response and identifies markers that are linked specifically to chemotherapy sensitivity, response or toxicity. Affordability StrandAdvantage provides an affordable opportunity to obtain faster and more actionable results compared to other tests. Clinical Utility of StrandAdvantage StrandAdvantage Test Performance Characteristics Validation Summary 100 Assay Validation Parameter Results 75 78% Assay Accuracy / concordance 95.8% 50 66% 67% Analytical sensitivity 100% Analytical specificity 95% 25 Reproducibility 99.7% 0 LUNG BREAST COLON Graph denotes percentage of cases where clinically actionable variation(s) were reported *Slightly lower specificity and concordance can be explained by the limitation of Sanger to detect SNPs at <30% supporting reads. Validation performed by Sanger sequencing. *Clinical utility and assay validation parameters are only applicable to the gene loci sequenced by NGS

10 The StrandAdvantage Testing Process From Prescription to Report Optimized to fit the needs of clinical practice, StrandAdvantage uses next-generation sequencing to analyze cancer-related genes taken from solid tumor samples. The test results are annotated using a comprehensive knowledge base curated by proprietary technology and an experienced team of scientists at Strand. Test Prescription Provide prescription to your patient for StrandAdvantage testing. Sample collection The hospital or our product specialist collects sample from patient in kits provided by us. Sample is sent to our lab for processing. Sample processing & analysis Samples are processed through state-of-the art analysis, interpretation, and reporting platforms by our team of expert scientists. Report Receive your clinical report securely through . The final results are delivered in an easy-to-read report containing actionable genomic variant information. Our clinical experts are available to help you review the results and answer any questions you may have. Sample Requirement to Perform StrandAdvantage Test Formalin-fixed, paraffin embedded tissue (FFPE) Turnaround Time (TAT) for StrandAdvantage Test StrandAdvantage Lung, Breast, Colon Cancer Tests 10 working days Complete 48 gene report 4 weeks

11 ATGCATGCATG ATGCATGCATG TGCA ATGCATG ATGCATGCATGA For Which of My Patients Should I Order the StrandAdvantage Test? Patients with solid tumors, especially those with breast, lung, and colon cancers for whom individual, tissue specific panels are available. Prior to starting therapy, as part of your molecular work-up. Patients who have failed first-line therapy, or have a metastatic presentation. During the neoadjuvant period and soon after surgery. Benefits of Using Strand s NGS-Based Multi-Gene Tests vs. Single Gene Tests Compared to single gene testing approaches, Strand s NGS-based multi-gene testing allows : Short TAT to start therapy, including first-line options. Testing of many genes concurrently (simultaneous identification of a driver mutation, as well as a secondary mutation in the gene). Identification of resistance to targeted therapy for the driver gene, thus helping predict the contraindications of a targeted drug. Targeting tumors of different origins with the same driver mutations, using a single drug. Testing a tumor for mutations and genes other than the ones typically associated with that tumor for more information. Determining with very high sensitivity extremely subtle mutations that are unique to the tumor. Capturing tumor heterogeneity with high sensitivity, often missed with other molecular testing approaches. We tested your tumor sample and looked at it under the microscope. The morphology of the tumor suggests the tumor may be of subtype X. IHC Evolution of Cancer Diagnostics s Histopathology MSI Biopsy Resection Specimen FISH NGS targeted panels Cytogenetics Single gene ATGCATGC Oncologists change in approach to cancer diagnosis and therapy selection The StrandAdvantage test indicates that your tumor contains actionable mutations which uniquely qualifies you for an alternate targeted drug therapy. Over the years, rapid advances in cancer diagnostic technology has enabled oncologists to obtain deeper insights about the patients tumor and genetics, thereby helping make informed and actionable therapy decisions for them.

12 About Strand A History of Innovative Genomic Research Founded in 2000, Strand Life Sciences is a personalized medicine company offering next-generation sequencing (NGS)-based, targeted multi-gene panels for cancer and other diseases. Strand works with oncologists, pathologists, and community hospitals to enable faster clinical decision support for accurate molecular diagnosis, prognosis, therapy recommendations, and clinical trials. Strand s central reference laboratories are located in Bangalore, India and Colorado, USA. For larger hospital systems, Strand offers an innovative customizable turnkey solution called Strand SmartLab ( Our genomics products and solutions are used at over 2,000 laboratories and 100 hospitals worldwide. A Trusted Partner to Companies Worldwide For 15 years, our products have facilitated the work of leading researchers and medical geneticists around the world. SCGPM-MKTG V2 Contact Us Get started with targeted cancer treatments. Order a test kit today or talk to one of our product specialists to learn more. Strand Center for Genomics & Personalized Medicine (A unit of Strand Life Sciences Pvt. Ltd.) UAS Alumni Association Building, Veterinary College Campus, Bellary Road, Hebbal, Bangalore Phone: , support.strandx@strandls.com,