Comprehensive Genomic Profiling, in record time. Accurate. Clinically Proven. Fast.

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1 Comprehensive Genomic Profiling, in record time Accurate. ly Proven. Fast.

2 PCDx advantages Comprehensive genomic profiling, in record time PCDx Comprehensive Genomic Profiling (CGP) provides precise information about the targetable cancer pathways in the tumor to allow for more effective clinical decision-making. Comprehensive genomic profiling on small tissue specimens With only 1/3 rd of the sample failure rate of other leading providers 3, Paradigm s success rate in profiling tumors with PCDx is 94%. 4 Through our proprietary library creation methods and other laboratory techniques that provide us with an average depth of coverage of >5x, we obtain comprehensive genomic profiling results on small tissue specimens with limited tumor (e.g. 5-1%), including fine needle aspirates (FNAs). Data on ~29 sequential samples submitted for PCDx Challenges presented by current CGP solutions Obtaining quality results on small tissue specimens A large percentage of tumor biopsies that are received by molecular laboratories have either a limited amount of tissue (e.g. FNAs) or low tumor cellularity (e.g. samples with 5-1% tumor). These present practical challenges when attempting to run comprehensive genomic testing for many patients unless an accurate test such as PCDx is run. Rapid turnaround time Advanced stage cancer patients typically progress rapidly. Often these patients are unable to obtain their next course of therapy due to worsening of condition. 1,2 There is a clinical need to obtain your testing results as fast as possible. ly meaningful results Tissue should be tested to maximize potential treatment options. A large number of reports are generated citing either unactionable genomic findings or inapplicable clinical trials. This creates practical challenges and frustration to the treating clinician when deciding what to do next ,723 Fastest turnaround time 123 PCDx Cases Run and Reported with insufficient DNA and mrna 52 PCDx cases cancelled prior to testing due to insufficient tissue 94% Sample Success Rate Paradigm delivers clinical results to our clients in 4 to 5 business days from receipt of the tissue sample. Our laboratory processes have been engineered to ensure a reduced time to next therapy and continuity of clinical care. Day 1 Sample is received and pathology confirms initial diagnosis with H&E. Successful PCDx Runs Day 2 Tumor DNA & RNA are extracted, purified and quantified. 175 Samples Insufficient for Testing Day 3 DNA & RNA library creation. Day 4 Sequencing and analysis. Day 5 interpretation of results, quality assurance performed and clinical report delivered. 1. Von Hoff, D. D., et al., Pilot study using molecular profiling of patients tumors to find potential targets and select treatments for their refractory cancers. Journal of Oncology, (21) 28(33), , 3. Kalyan C. Mantripragada, et al., Accrual Targeting Genomic Alterations After Next-Generation Sequencing at a n-national Cancer Institute Designated Cancer Program. Journal of Oncology Practice (216) 12:4, e396-e44. 4, 6. Paradigm s sample rejection rate is approximately ~6% vs. 18% as seen for other leading platforms (Matripragada et al. Journal of Oncology Practice. 216). Paradigm internal data set and analysis on first 27 patients run on the PCDx platform where only 175 patients had insufficient tissue for analysis.

3 ly proven & actionable Paradigm PCDx is a comprehensive genomic profiling (CGP) test that interrogates the key drivers of cancer: DNA, RNA and. s Changes in the DNA sequence, including insertions, deletions and base substitutions. Somatic mutation analysis has become standard of practice for solid tumors in order to identify therapeutic sensitizing and resistance mutations (e.g., EGFR, KRAS, BRAF). Test Description: Test Name: Paradigm Cancer Diagnostic (PCDx) Carcinoma of Unknown Primary Tumor Diagnosis: Collection Site: Right Supraclavicular region Specimen Type: Block Case/Specimen ID: Specimen Collected: Specimen Received: Next-Generation Sequencing () assays analyzing mutations, copy number variations, messenger RNA levels and select protein expression by Immunohistochemistry () as may be requested, all tied to levels of evidence relative to an associated treatment. BRAF Actionable EGFR (ERBB1) HRAS KRAS NRAS PIK3CA Ver: PCDx Copy Number Variation Gene Fusions HER2 (ERBB2) Actionable ROS1 amphiregulin (AREG) Actionable CDA ERBB3 epiregulin (EREG) VEGFR2 (KDR) MET TUBB3 TS (TYMS) TUBB3 AR Negative TS (TYMS) ROS1 hent1 (SLC29A1) Negative MGMT TOP1 Changes in the protein expression as measured by have been utilized for many years as the gold-standard to quantitate the actual translation of altered gene products. Our ability to interrogate key protein markers (e.g. PD-L1, HER2, AR, MGMT, TOP1) provides insights on potential response to hormonal manipulations, cytotoxic, targeted, and immuno-oncology agents as well as emerging clinical trials. On Compendia Driven Strategies Irinotecan TOP1 3+ 5% Yes Yes Off Compendia Driven Strategies Ceritinib Crizotinib Gene Fusion ROS1 Ado-trastuzumab emtansine Lapatinib Pertuzumab Trastuzumab CNV HER2 (ERBB2) Cetuximab Panitumumab BRAF HRAS Cetuximab of : L1 = 1 / LII-1 = II-1 / = II-2 / = II-3 / Gene expression is the process by which information from a gene is used in the synthesis of a functional protein. Sequencing-based mrna expression analysis enables the significant multiplexing of biomarker targets (e.g., ER, ERCC1). LIII = III / = Different Tumor Type 445 N. Fifth Street, Suite 3 Paradigm Diagnostics, Inc CLIA# 3D Phoenix, AZ Report Date: 4/7/ of 12 Sample Patient 7 1/1/1974 Sample Report Sample Doctor Sample Cancer Center Test Name: Paradigm Cancer Diagnostic (PCDx) Tumor Diagnosis: Breast Cancer - Invasive Collection Site: Left Breast Specimen Type: Block Case/Specimen ID: Specimen Collected: Specimen Received: Test Description: Next-Generation Sequencing () assays analyzing mutations, copy number variations, messenger RNA levels and select protein expression by Immunohistochemistry () as may be requested, all tied to levels of evidence relative to an associated treatment. Specimen Image: PIK3CA c.1633g>a p.e545k Actionable BRCA1 BRCA2 ER (ESR1) CCND1 Actionable HER2 (ERBB2) Ver: PCDx amphiregulin (AREG) Actionable BCL-2 survivin (BIRC5) BRCA1 IGF1R SSTR2 TOPO IIa TUBB3 AR t Changed HER2 (ERBB2) t Changed ER (ESR1) t Changed PR (PGR) t Changed AR Actionable CA IX Negative hent1 (SLC29A1) PDL1 TILs Negative PDL1 Tumor PTEN TOP1 TP (TYMP) TRKpan Negative TP (TYMP) 2+ 3% Letrozole RNA BCL x Bevacizumab Doxorubicin Epirubicin CA IX Negative + 1% hent1 2+ 8% Doxorubicin Epirubicin Gemcitabine TOPO IIa % 5.3 % PFS > 1.3 PFS > 1.3 Patients treated with genomically guided therapy had a superior median PFS compared to those treated with non-genomically guided therapy (86 days vs. 49 days, p=.5, H.R.=.55, 95% C.I.: ). PCDx provides associations for the most drug therapies. PCDx associates with >8 single agent drugs and combination therapies including: Standard Chemotherapies Hormonal Therapies RNA Capecitabine % 43.2 % Somatic rearrangements are usually result in the formation of a fusion gene, derived from two disrupted normal genes, from which a fusion transcript and protein is generated. (e.g., EML4-ALK) On Compendia Driven Strategies 4 4 Genomically Genomically n-genomically n-genomically Pathologist H&E was performed and the percent tumor available for analysis was 95% Patient's Select Cancer Genomic & Proteomic Landscape Copy Number Variation p <.1 p < Rearrangements & Gene Fusions Patient Name: Patient DOB: PCDx Case#: Ordering Physician: Ordering Location: Proportion of Patients Achieving a PFS Ratio > 1.3 Proportion of Patients Achieving a PFS Ratio > 1.3 CNVs are alterations of the DNA of the cancer genome that result in the cell having abnormal copies of one or more sections of the DNA. These alterations can have a significant impact on response to therapy (e.g., HER2). Pathologist H&E was performed and the percent tumor available for analysis was 9 Specimen Image: Patient's Select Cancer Genomic & Proteomic Landscape Copy Number Variations In an independent clinical study, genomically directed therapy guided by Paradigm PCDx improved progression free survival as compared to non-genomically guided therapy.5 Percent Percent of Patients of Patients Sample Patient 12 1/1/1911 Sample Report Sample Doctor Sample Cancer Center Patient Name: Patient DOB: PCDx Case#: Ordering Physician: Ordering Location: Supported by published clinical data 29.6x Targeted Agents (TKIs and MABs) Immunotherapies s. Off Compendia Driven Strategies Sorafenib + carboplatin, paclitaxel of : L1 = 1 / LII-1 = II-1 / = II-2 CNV CCND1 / = II-3 / Paradigm Diagnostics, Inc CLIA# 3D N/A LIII = III / = Different Tumor Type 445 N. Fifth Street, Suite 3 Phoenix, AZ Report Date: 8/31/ of 11 5, 7. R adovich, M., et al., benefit of a precision medicine based approach for guiding treatment of refractory cancers. Oncotarget, (216) 7(35),

4 PCDx can help identify the best cancer treatment options for you today. Start getting better results, faster. Accurate. 5x average depth of coverage Low sample rejection (QNS) rates (6% vs. 18%)6 ly Proven. Analyzes Tumor DNA, RNA & Prospective data published showing improvement in Progression Free Survival (PFS)7 Provides associations to >8 single agent and combination therapies Full PCDx results possible from >5% tumor; including FNAs Fast. delivered in 4 to 5 business days Reduces time to next therapy Ensures continuity of clinical care For more information, please contact Client Services at or visit paradigmdx.com

5 Paradigm Diagnostics, Inc. 445 N. 5th Street, Suite 3 Phoenix, AZ paradigmdx.com

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