# 1 India s Best Selling Cancer Genomics Test Precision treatment for every Cancer Patient Patient Guide

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1 # 1 India s Best Selling Cancer Genomics Test Precision treatment for every Cancer Patient Patient Guide PositiveSelect is India s widely used Cancer Genomics test with every 8 out of 10 patients opting for PositiveSelect PositiveSelect is available as 4 different tests offering solutions for every type of cancer patient Genomics is finally affordable to every patient

2 Dear Valued Customer, Bioscience our job is to provide you, our customer, with the very best and highest quality test. The goal of PositiveSelect is to help you get on the best treatment. Positive Bioscience was established with the goal of providing the best possible technology India s Leading Cancer Genomics Testing Company. Positive Bioscience thanks you for considering our testing and we look forward to serving you. Yours Sincerely, Dr. Sandhya Iyer Senior Scientific Officer

3 Key benefits of PositiveSelect 1 Aids routine molecular diagnostics 2 Improve Treatment Outcome by upto 300% PositiveSelect aids routine molecular diagnostics in Lung, Colorectal cancer (CRC), Melanoma, Gastric and Ovarian Cancer PositiveSelect checks millions of data points and hundreds of treatment options to select the best one It covers >80% of routine molecular diagnostics in Breast, Head and Neck, Prostate and Pancreatic cancer Treatment recommendations are tailored to the patient s genetic profile 3 4 Cut Treatment Costs Reduce Side Effects PositiveSelect removes the trial and error approach Getting on the best treatment quickly saves money PositiveSelect helps to avoid dangerous and toxic side effects Treatments selected based on genetic profiling minimize side effects 5 Most Comprehensive Test 6 All Cancer types Covered PositiveSelect tests for hundreds of genes on Next Generation Sequencing (NGS) PositiveSelect can test every cancer type and stage Every gene is tested 1000 times to ensure accuracy If tumor is not available we test on blood (Ct-DNA) Tests for all types of genomic alterations, mutations, insertions, deletions, translocations, fusions, rearrangements and amplifications

4 Features and Features Benefits Tests performed Universal Molecular Diagnostics Sample Requirement (FFPE/Blood) Patient profile Genes Industry leading coverage Indels/ Base Substitutions/ Amplifications/ Rearrangements/ Fusions Sensitivity Specificity Pharmacogenomics Off Label Drugs True Somatic Mutations True Germline Mutations Pathway Analysis Tumour Mutation Load MSI (Microsatellite instability) Driver Mutations Expert Commentary Expert Consultation Number of tests performed Aids conventional molecular diagnostics Convenience and accuracy in molecular profiling Ideal patients for the test Number of Genes tested Improves accuracy Drug response and prognosis Test with > 90% sensitivity is considered gold standard Test with > 90% specificity is considered gold standard Drug response and prognosis Treatment options outside guidelines True actionable driver mutations Hereditary association Accurate treatment decisions Useful for Immunotherapy Useful for Immunotherapy Helps in determining precise treatment options Helps treating clinican understand genetic perspective Consultation with genetic expert to precise treatment

5 Benefits of Product PositiveSelect Lite PositiveSelect Plus PositiveSelect Match PositiveSelect Ultimate Introductory test for newly diagnosed patients Intermediate test for first line failures Advanced test for advanced cancers Most advanced test for advanced cancers Tumour Sample Only Tumour Sample Only Tumour Sample + Normal Sample Tumour Sample + Normal Sample Newly Diagnosed 1st Line failure/ Rare Cancers 1st Line failure/ Family history of cancer/relapse Aggressive/rare cancer/patients with no treatment options as per guidelines x 1000x 1000x x 1000x x >90% >90% >90% >90% >90% >90% >90% >90% 31% more accurate 31% more accurate As cancer is a life-threatening disease Positive Bioscience recommends PositiveSelect Ultimate for every patient for best chances of survival

6 Genomic profiling in Cancer Cancer is a genetic disease caused by changes in DNA These changes trigger an abnormal cell growth which forms tumour that invade healthy organs and tissue Many genes can cause cancer Two people having same cancer affecting the same body part are most likely different at genetic level and will respond differently CANCER CAUSING GENES CANCER BRCA1, BRCA2, STK11, TP53, PTEN, CDH1, PALB2, ATM, CHEK2, NBN, BARD1, BRP1, RAD51C Breast STK11, APC, BMPR1A, SMAD4, APC, BMPR1A, SMAD4, MUTYH, TP53, PTEN, CDH1, CHEK2 Colorectal MLH1, MSH2, MSH6, PM52, EPCAM, STK11, TP53, PTEN Endometrial MLH1, MSH2, MSH6, PM52, EPCAM, STK11, APC, BMPR1A, SMAD4, TP53, CDH1 Gastric BRCA1, BRCA2, CDKN2A, CDK4, TP53 Melanoma MLH1, MSH2, MSH6, PMS2, EPCAM, STK11, TP53, BRP1, RAD51C, RAD51D Ovarian APC, BMPR1A, SMAD4, CDKN2A, CDK4, TP53, PALB2, ATM Pancreatic BRCA1, BRCA2, TP53, CHEK2, NBN Prostate Most cancer patients dont respond to standard treatment Cancer patients are often treated by the one-size-fits-all regimen > 50 %* Many cancer patients fail in their first line therapy

7 Patients treated as per genomic profile lives 60% more Genomic Profile not Done Standard Therapy Lung Cancer Patients Genomic Profile Done Gefitinib ALK Crizotinib HER2 Trastuzumab Lives 60% more compared to patients who have not done genomic profiling Genomic profiling increases your chances of survival by Identifying genetic variations that can be targeted using better Targeted therapies (e.g Gefitinib in positive cases) Helps avoid drugs which will be ineffective thereby reducing side effects (e.g. KRAS mutation to determine efficacy of Cetuximab) All American Hospitals use Cancer Genomics Testing 1. MD Anderson 2. Memorial Sloan Kettering 3. Mayo Clinic 4. Dana Farber 5. Johns Hopkins (Mutation) ALK (Rearrangement) KRAS (Mutation) ROS1 (Rearrangement) RET (Rearrangement) PD-L1 (Expression) BRAF (Mutation) ER (Expression) VEGF (Mutation) BCR-ABL (Translocation) MTOR (Mutation) Trastuzumab Crizotinib Cetuximab Crizotinib Cabozantinib Pembrolizumab Vemurafenib Tamoxifen Bevacizumab Imatinib/Dasatinib/Nilotinib Everolimus

8 Lite Single moleular diagnostic test covers all routine molecular tests Tests for 100 genes including, KRAS, PIK3CA, HER2, BRAF, ALK, ROS1, RET, available at affordable price Covers nearly all National Comprehensive Cancer Network (NCCN) recommendations in a single test PositiveSelect Lite also gives drug recommendations associated with the 100 genes that are tested PositiveSelect is a must do test for All newly diagnosed solid tumours Patients looking for molecular diagnostic tests Ideal for newly diagnosed solid tumours PositiveSelect aids routine molecular diagnostics All NCCN genes covered Complete Replacement Lung, Colorectal (CRC), Kidney, Ovarian cancer Lite Most (80%) NCCN genes covered Add On Tests Breast, Prostate, CNS, Head and Neck cancer List of important genes covered as per Cancer type Lung Breast Ovarian CRC Pancreatic Prostate Kidney, ALK, KRAS, HER2, BRAF,, ROS1, RET HER2, BRCA1, BRCA2, TP53, ESR1 BRCA1, BRCA2 NRAS, KRAS, BRAF, TP53, MLH1, MSH2, MSH6 KRAS, TP53, PTEN, AR, BRCA1, BRCA2 VHL

9 Lite PositiveSelect Lite Technical Specification Genes Analyzed 100 Sequencing Method Illumina Next Generation Sequencing Bioinformatics Use of our trademark TEST (Targeted Enrichment Sequencing for Therapeutics) pipeline for analysis and annotation Assay Sensitivity >90% Assay Specificity >90% Sequencing Coverage 1000x Turnaround Time 4 weeks Ideal for newly diagnosed solid tumours Sample Types Sample Requirements DNA Input Required Whole Blood or Tumour 6-8 ml of blood each in 2 Streck tubes Or FFPE sample (tissue size >=40µm having atleast 30% malignant cells) ng PositiveSelect Lite: Testing Process Sample Required Biomarkers Tested Lite Bioinformatics Reporting or FFPE sample or 6-8ml of Blood each in 2 Streck tubes 100 cancer driving genes at 1000x coverage Routine molecular diagnostics and Pharmacogenomics Aids routine diagnostics

10 Lite Page 1 of Report: Pharmacogenomics Section Easy to understand report format Pharmacogenomics information given on the first page Second page covers molecular testing details Ideal for newly diagnosed solid tumours Name : Gender : PATIENT XXX Name : Dr. XXX F Date of Birth : --/--/---- Institute : XXX Hospital PHYSICIAN Diagnosis : Squamous Cell Carcinoma of Lung SAMPLE Sample Type : Plasma Sample Collection Date : --/--/2017 Sample ID : PB_CG_SL_ _X Test : PositiveSelect Lite Technology : Illumina NGS Coverage : 1000x Report Date : --/--/2017 Patient Tumor Type Specific Genes Gene Genetic Alteration Result AKT1 ALK BRAF DDR2 ERBB2 Therapies with benefit highlighted by a green tick Exon 19 deletion [Glu746_Ala750del] Positive FGFR1 KRAS MAP2K1 NRAS Therapies with lack of benefit highlighted by a red tick PIK3CA PTEN RET ROS1 Note: All the genomic alterations relevant to the cancer type (Lung Cancer) and the associated genes as per NCCN and mycancergenome.org are reported here.

11 Lite Genes Covered in PositiveSelect Lite POINT MUTATIONS (>99% Sensitivity) ABCB1 CYP19A1 ERCC2 JAK2 PARP1 ABCC1 CYP1A1 ERCC3 JAK3 PDCD1 (PD1) ABCC2 CYP1A2 ERCC4 KDR PDGFRA ABCC3 CYP1B1 ERCC5 KIT PDGFRB ABCC4 CYP24A1 ESR1 (ER) KRAS PGR (PR) ABCG2 CYP27B1 EWSR1 LINS1 PIK3CA ABL1 CYP2B6 EZH2 MAP2K1 PTEN AKT1 CYP2C19 F2R MAP2K2 REL ALK CYP2C9 FGFR1 MAPK1 RET AR CYP2E1 FGFR2 ROS1 BCR CYP3A4 FGFR4 MLH1 RRM1 BRAF CYP3A5 FLT3 MSH2 STAT3 BRCA1 DCK GSTA1 MSH6 TERT BRCA2 DDB1 GSTP1 MTHFD1 TOP1 BTK DDR2 HIF1A MTHFR TP53 CCND1 DYNC2H1 HRAS MTOR TSC1 CCND2 IDH1 NF1 TSC2 CDA EML4 IGF1R NR1I2 VEGFA CDK4 ERBB2 (HER2) IL6 NR1I3 VHL CDK6 ERCC1 JAK1 NRAS XRCC1 FUSIONS (>90% Sensitivity) ALK AR AMPLIFICATIONS BRAF INSERTION/DELETIONS (INDELS) (>95% Sensitivity) BRCA1 MTOR FGFR2 CCND1 CDK4 NF1 RET CCND2 ERBB2 PDGFRA ROS1 ERBB2 FGFR1 KIT PTEN Ideal for newly diagnosed solid tumours FGFR2 KRAS PIK3CA KIT PDGFRA MLH1 TP53 TSC1 VHL

12 Plus Comprehensive genomic profiling using Next Generation Sequencing Tests 350 genes PositiveSelect Plus detects all classes of genomic alterations, including point substitutions, insertions and deletions (indels), copy number alterations (CNAs) and rearrangements using cfdna or FFPE sample Industry leading coverage of 1000x Ideal for 1st line failure/rare cancers Benefits of PositiveSelect Plus Identifies genomic alterations associated with clinical benefit Provides Targeted Therapy Gives information on Tumour Mutation Burden Gives information on Microsatellite Instability Status Quantifies clinical markers associated with immunotherapy response Identifies relevant Clinical Trials

13 Genes Analyzed 350 Plus PositiveSelect Plus Technical Specification Sequencing Method Bioinformatics Illumina Next Generation Sequencing Use of our trademark TEST (Targeted Enrichment Sequencing for Therapeutics) pipeline for analysis and annotation Assay Sensitivity >90% Assay Specificity >90% Sequencing Coverage 1000x Turnaround Time 4 weeks Ideal for 1st line failure/rare cancers Sample Types Sample Requirements DNA Input Required Whole Blood or Tumour 6-8 ml of blood each in 2 Streck tubes Or FFPE sample (tissue size >=40µm having atleast 30% malignant cells) ng PositiveSelect Plus: Testing Process Sample Required Biomarkers Tested Bioinformatics Reporting or Plus FFPE sample or 6-8 ml of Blood each in 2 Streck tubes 350 cancer driving genes at 1000x coverage Mapping for treatment options and clinical trials Contains PGX, TMB, MSI

14 Plus Report Ideal for 1st line failure/rare cancers PLUS Name : Gender : PATIENT XXX Name : Dr. XXX M Date of Birth : --/---/---- Institute : XXX Hospital PHYSICIAN SAMPLE Diagnosis : Pancreas Adenocarcinoma Sample Type : Plasma Sample Collection Date : --/---/2017 Sample ID : PB_CG_SP_ _X Test : PositiveSelect Plus Technology : Illumina NGS Coverage : 1000x Report Date : --/---/2017 Gene TP53 KRAS CDKN2A SMAD4 GENOMIC ALTERATIONS PATIENT TUMOR WITH THERAPEUTIC TYPE SPECIFIC IMPLICATIONS GENES Genetic Alteration p.g12d c.131dupa Result Positive Positive Additional Findings Microsatellite status MS-Unstable Tumor Mutation Burden TMB-High Positive Positive Note: All the genomic alterations relevant to the cancer type (Pancreas Adenocarcinoma) and the associated genes as per NCCN are reported here.

15 Plus Genes Covered in PositiveSelect Plus POINT MUTATIONS (>99% Sensitivity) ABCB1 ABCC1 ABCC2 ABCC4 ABCG2 ABL1 AKT1 AKT2 AKT3 ALK ALOX12B AMELY APC AR ARAF ARID1A ASXL1 ASXL2 ATM ATR ATRX AURKA AURKB AXIN1 AXIN2 AXL B2M BAP1 BARD1 BBC3 BCL2 BCL2L1 BCL2L11 BCL6 BCOR BCR BLM BRAF BRCA1 BRCA2 BRD4 BRIP1 BTK CARD11 CASP8 CBFB CBL CCND1 CCND2 CCND3 CCNE1 CD274 CD276 CD79B CDC73 CDH1 CDK12 CDK4 CDK6 CDK8 ALK FGFR2 FGFR3 RET ROS1 NTRK1 AR CCNE1 CCND1 CCND2 ERBB2 FGFR2 KRAS PIK3CA MYC PD-L1 BRAF CDK4 CDK6 FGFR1 KIT PDGFRA RAF1 ATM APC ARID1A BRCA1 BRCA2 CDH1 CDKN2A ERBB2 GATA3 KIT MLH1 MTOR NF1 PDGFRA PTEN RB1 SMAD4 STK11 TP53 TSC1 VHL CDKN1A CDKN1B CDKN2A CDKN2B CDKN2C CHEK1 CHEK2 CREBBP CRKL CRLF2 CSF1R CTCF CTLA4 CTNNB1 CUL3 CYP19A1 CYP1A1 CYP1A2 CYP1B1 CYP2A4 CYP2A6 CYP2B6 CYP2E1 DAXX DAZ1 DDR2 DICER1 DIS3 DNMT1 DNMT3A DNMT3B DOT1L E2F3 EGFL7 EML4 EP300 EPCAM EPHA3 EPHA5 EPHB1 ERBB2 ERBB3 ERBB4 ERCC2 ERCC3 ERCC4 ERCC5 ERG ESR1 ETV1 ETV6 EWSR1 EZH2 FAM123B FANCA FANCC FAT1 FBXW7 FGF19 FGF3 FGF4 FGFR1 FGFR2 FGFR3 FGFR4 FH FLCN FLT1 FLT3 FLT4 FOXA1 FOXL2 FOXP1 FUBP1 GATA1 GATA2 GATA3 GNA11 GNAQ GNAS GSK3B GSTA1 GSTP1 HGF HIF1A HIST1H3B HNF1A HRAS IDH1 IDH2 IFNGR1 IGF1 IGF1R IGF2 IKBKE IKZF1 IL10 IL7R INSR IRF4 IRS1 IRS2 JAK1 JAK2 JAK3 JUN KDM5A KDM5C KDM5D KDM6A KDR KEAP1 KIT KLF4 KRAS LATS1 LATS2 LMO1 MAP2K1 MAP2K2 MAP2K4 MAP3K1 MAP3K13 MAPK1 MAX MCL1 MDC1 MDM2 MDM4 MED12 MEF2B MEN1 MITF MLH1 MLL MLL2 MLL3 MPL MSH2 MSH6 MTHFD1 MTHFD1L MTHFR MTOR MUTYH MYC MYCL1 MYCN MYD88 MYOD1 NBN NCOR1 NF1 NF2 NFE2L2 NKX2-1 NKX3-1 NOTCH1 NOTCH2 NOTCH3 NOTCH4 NPM1 NR1I2 NRAS NSD1 NTRK1 NTRK2 NTRK3 NUTM1 PAK1 PAK7 PALB2 PARK2 PARP1 PAX5 PAX8 PBRM1 PDCD1 PDGFRA PDGFRB PDPK1 PGR PIK3C2G PIK3C3 PIK3CA PIK3CB PIK3CD PIK3CG PIK3R1 PIK3R2 PIK3R3 PIM1 PLK2 PMAIP1 PMS1 PMS2 PNRC1 POLE PPP2R1A PRDM1 PRKAR1A PRKY PTCH1 PTEN PTPN11 RAC1 RAD50 RAD51 RAD51B RAD51C RAD51D RAD52 RAD54L RAF1 RARA RASA1 RB1 RECQL4 REL RET RFWD2 RHOA RICTOR RIT1 RNF43 ROS1 RPS4Y2 RPS6KA4 RPS6KB2 RPTOR RUNX1 RYBP SDHA SDHAF2 SDHB SDHC SDHD SETD2 SF3B1 SH2D1A SLC22A1 SMAD2 SMAD3 SMAD4 SMARCA4 SMARCB1 SMO SOCS1 SOX17 SOX2 SOX9 SPOP SRC SRY STAG2 STK11 STK40 SUFU SYK TBX3 TERT TET1 TET2 TGFBR1 TGFBR2 TMEM127 TMPRSS2 TNFAIP3 TNFRSF14 TOP1 TP53 TP63 TRAF7 TSC1 TSC2 TSHR TSPY4 TTTY23 TYMS U2AF1 USP9Y VHL WT1 XIAP XPO1 YAP1 YES1 ZFY FUSIONS (>99% Sensitivity) INSERTION/DELETIONS (INDELS) (>95% Sensitivity) AMPLIFICATIONS Ideal for 1st line failure/rare cancers

16 Match PositiveSelect Match is India s first Cancer Genomics test which tests both tumour and normal sample Testing variations in both tumour and normal sample helps identify true somatic mutations which are driving cancer. Once true driver mutations are identified patients can be treated with confidence 100 genes tested on NGS in tumour and normal sample Helps find out true somatic and germline mutations Improves accuracy of finding driver mutation by 31% Provides better treatment options thereby improving survival chances Benefits of PositiveSelect Match Identifies true driver mutations Identifies true Somatic mutations Ideal for 1st line failure/family history of cancer/relapse Identifies Germline mutations Improves accuracy of Genomic Profiling by 31% Universal diagnostics Identifies HBOC, Lynch Syndrome Helps in knowing risk of inheritance of faulty genes in the family

17 Genes Analyzed 100 Match PositiveSelect Match Technical Specification Sequencing Method Bioinformatics Illumina Next Generation Sequencing Use of our trademark TEST (Targeted Enrichment Sequencing for Therapeutics) pipeline for analysis and annotation Assay Sensitivity >90% Assay Specificity >90% Sequencing Coverage 1000x Turnaround Time 4 weeks Ideal for 1st line failure/family history of cancer/relapse Sample Types Sample Requirements DNA Input Required Blood in Streck tubes and in EDTA tube or Tumour and Whole Blood in EDTA tube 6-8 ml of blood each in 2 Streck tubes and 3-4 ml of blood in EDTA tube or FFPE sample and 3-4 ml of blood in EDTA tube ng PositiveSelect Match: Testing Process Match Sample Required Biomarkers Tested Bioinformatics Reporting or FFPE sample or 6-8ml of Blood each in 2 Streck tube & 4ml in EDTA tube 100 cancer driving genes on tumour and normal sample at 1000x Mapping for treatment options and clinical trials Report contains PGX, True Germline, True Somatic Mutations

18 Report Match Easy to understand report format Pharmacogenomics information given on the first page followed by molecular tests Green tick indicates beneficial treatment options Red tick denotes treatment options with lack of benefit Ideal for 1st line failure/family history of cancer/relapse PATIENT PHYSICIAN Name : XXX Name : Dr. XXX Gender : F Date of Birth : --/---/---- Institute : XXX Hospital SAMPLE Diagnosis : Ca Peritoneal Ovarian Sample Type : Plasma with Renal Mets Sample Collection Date : --/---/2017 Sample ID : PB_CG_SM_2016_X Test : PositiveSelect Match Technology : Illumina NGS Coverage : 1000X Report Date : --/---/2017 Drugs mtor/pik3ca inhibitors [Everolimus, Temsirolimus/ Buparlisib, Taselisib] THERAPIES WITH POTENTIAL BENEFIT Gene PIK3CA [E542K] Result Positive Targeted Pathways PI3K/MTOR signaling pathway Therapies with benefit highlighted by a green tick MEK Inhibitors [Trametinib] KRAS [G13C] Positive KRAS/BRAF/MAPK signaling pathway Drugs inhibitors [Cetuximab/Panitumumab] THERAPIES WITH POTENTIAL LACK OF BENEFIT Gene KRAS [G13C] Result Positive Targeted Pathways KRAS/BRAF/MAPK signaling pathway Therapies with lack of benefit highlighted by a red tick PARP inhibitors BRCA1/2 Homologous Recombination [Olaparib] Note: Patients with mutated KRAS are less likely to benefit from inhibitors (Cetuximab and Panitumumab) No germline pathogenic variants detected in BRCA1/2 genes. Hence the patient is less likely to benefit from PARP inhibitors (Olaparib)

19 Match Genes Covered in PositiveSelect Match POINT MUTATIONS (>99% Sensitivity) ABCB1 CYP19A1 ERCC2 JAK2 PARP1 ABCC1 CYP1A1 ERCC3 JAK3 PDCD1 ABCC2 CYP1A2 ERCC4 KDR PDGFRA ABCC3 CYP1B1 ERCC5 KIT PDGFRB ABCC4 CYP24A1 ESR1 (ER) KRAS PGR (PR) ABCG2 CYP27B1 EWSR1 LINS1 PIK3CA ABL1 CYP2B6 EZH2 MAP2K1 PTEN AKT1 CYP2C19 F2R MAP2K2 REL ALK CYP2C9 FGFR1 MAPK1 RET AR CYP2E1 FGFR2 ROS1 BCR CYP3A4 FGFR4 MLH1 RRM1 BRAF CYP3A5 FLT3 MSH2 STAT3 BRCA1 DCK GSTA1 MSH6 TERT BRCA2 DDB1 GSTP1 MTHFD1 TOP1 BTK DDR2 HIF1A MTHFR TP53 CCND1 DYNC2H1 HRAS MTOR TSC1 CCND2 IDH1 NF1 TSC2 CDA EML4 IGF1R NR1I2 VEGFA CDK4 ERBB2 (HER2) IL6 NR1I3 VHL CDK6 ERCC1 JAK1 NRAS XRCC1 FUSIONS >90% Sensitivity ALK FGFR2 RET ROS1 Ideal for 1st line failure/family history of cancer/relapse AMPLIFICATIONS AR BRAF CCND1 CDK4 CCND2 ERBB2 FGFR1 FGFR2 KIT KRAS PIK3CA PDGFRA INSERTION/DELETIONS (INDELS) >90% Sensitivity BRCA1 ERBB2 KIT MLH1 MTOR NF1 PDGFRA PTEN TP53 TSC1 VHL

20 Ultimate Most comprehensive Cancer Genomics test available Matched NGS analysis on Tumour and Normal sample, testing 350 genes Only cancer genomics test in the world which covers: Pathway Analysis Tumour Mutation Burden (TMB) Microsatellite Instability (MSI) True Somatic Mutations True Germline Mutations Targeted Therapy Chemotherapy Clinical Trial Hereditary testing for HBOC and Lynch Syndrome Benefits of PositiveSelect Ultimate Provides the best chance of beating cancer Provides a 3D view of genomic profiling by accurately determining True Somatic, True Germline and True Driver mutations Provides treatment solution based on cancer pathways increasing the odds of beating cancer manyfold Immunotherapy options based on Microsatellite instability and Tumour Mutation Burden Expert commentary with every report Ideal for aggressive/rare cancers and patients with no treatment options Expert consultation with treating doctor to analyse and treat patients in a holistic manner

21 Ultimate PositiveSelect Ultimate Technical Specification Genes Analyzed 350 Sequencing Method Bioinformatics Illumina Next Generation Sequencing Use of our trademark TEST (Targeted Enrichment Sequencing for Therapeutics) pipeline for analysis and annotation Assay Sensitivity >90% Assay Specificity >90% Sequencing Coverage 1000x Turnaround Time 4 weeks Ideal for aggressive/rare cancers and patients with no treatment options Sample Types Sample Requirements DNA Input Required Blood in Streck tubes and in EDTA tube or Tumour and Whole Blood in EDTA tube 6-8 ml of blood each in 2 Streck tubes and 3-4 ml of blood in EDTA tube or FFPE sample and 3-4 ml of blood in EDTA tube ng PositiveSelect Ultimate: Testing Process Ultimate Sample Required Biomarkers Tested Bioinformatics Reporting or FFPE sample or 6-8ml of Blood each in 2 Streck tubes & 4ml in EDTA tube 350 cancer driving genes on tumour and normal sample at 1000x Mapping for treatment options and clinical trials Most comprehensive Cancer Genomics report

22 Ultimate First Page of Report: Expert Commentary and Summary Simple easy to understand report format Expert summary, genomic highlights and response to immunotherapy given on first page First page helps summarise the report for quick reference All important points highlighted on the first page makes the report more meaningful Ideal for aggressive/rare cancers and patients with no treatment options PATIENT PHYSICIAN Name : XXX Name : Dr. XXX Gender : M Date of Birth : --/---/---- Institute : XXX Hospital SAMPLE Signet ring cell carcinoma Diagnosis : Sample Type : Plasma & Blood of stomach cancer Sample Collection Date : --/---/2017 Sample ID : PB_CG_SU_ _X Test : PositiveSelect Ultimate Technology : Illumina NGS Coverage : 1000X Report Date : --/---/2017 EXPERT COMMENTARY The patient was diagnosed with signet-ring cell carcinoma of the stomach with lower esophagus, gastric cardia and fundus metastases and was treated with chemotherapy. We identified six clinically actionable genomic alterations [BRCA2 (T2412I), CDK4, NOTCH4, KRAS, and FGF19 amplification] and high tumor mutation burden. Studies have documented the effect of NOTCH4 amplification which continously activates PI3K/AKT/MTOR pathway inturn resulting in tumorigenesis. Gamma secretase inhibitors targeting NOTCH4 receptors and MTOR inhibitor could prove beneficial. CDK4 amplification could possibly result in enhanced and highly active CCND1-CDK mediated cell cycle and proliferation which when targeted using CDK4/6 inhibitors could promote anti-tumor activity. Amplification of KRAS could result in PIK3CA/MTOR or BRAF/MAPK activation, which may lead to increase in cell-proliferation and survival, which when inhibited using PIK3CA/MEK inhibitor could prove beneficial. Expert Commentary helps understand the genetic basis of the disease to take more actionable clinical decisions The total tumor mutation burden was detected to be high at mutations per megabase. This indicates that the patient may be a candidate for immunotherapy in an investigational setting. Note: Complimentary call for consultation is available. GENOMIC HIGHLIGHTS 4 Pathways driving cancer 7 Genomic alterations 6 Genomic alterations with clinical actionability 0 Genomic alterations with clinical lack of bene t 4 Clinical trials Microsatellite status Tumor Mutation Burden Note: TMB-Low :- <19 mutations/mb, TMB-High - >20 mutations/mb; IMPLICATIONS TO IMMUNOTHERAPY NOTCH4 mediated MTOR signaling pathway KRAS signaling pathway Cell cycle signaling pathway DNA repair pathway NOTCH4 - Amplification KRAS - Amplification (equivocal) CDK4 - Amplification (equivocal) FGF19 - Amplification (equivocal) MUTYH - A95W BRCA2 - T2412I MSI-Stable TMB-High MS-Stable <2% unstable sites, MS-Unstable >2% unstable sites Genomic Highlights: Summarises the pathways driving cancer in the patient. Once pathway is identified it can be targeted. Response to Immunotherapy: Summarises status of Tumour Mutation Burden and Microsatellite Instability

23 Ultimate Genes Covered in PositiveSelect Ultimate POINT MUTATIONS (>99% Sensitivity) ABCB1 ABCC1 ABCC2 ABCC4 ABCG2 ABL1 AKT1 AKT2 AKT3 ALK ALOX12B AMELY APC AR ARAF ARID1A ASXL1 ASXL2 ATM ATR ATRX AURKA AURKB AXIN1 AXIN2 AXL B2M BAP1 BARD1 BBC3 BCL2 BCL2L1 BCL2L11 BCL6 BCOR BCR BLM BRAF BRCA1 BRCA2 BRD4 BRIP1 BTK CARD11 CASP8 CBFB CBL CCND1 CCND2 CCND3 CCNE1 CD274 CD276 CD79B CDC73 CDH1 CDK12 CDK4 CDK6 CDK8 ALK FGFR2 FGFR3 RET ROS1 NTRK1 AR CCNE1 CCND1 CCND2 ERBB2 FGFR2 KRAS PIK3CA MYC PD-L1 BRAF CDK4 CDK6 FGFR1 KIT PDGFRA RAF1 ATM APC ARID1A BRCA1 BRCA2 CDH1 CDKN2A ERBB2 GATA3 KIT MLH1 MTOR NF1 PDGFRA PTEN RB1 SMAD4 STK11 TP53 TSC1 VHL CDKN1A CDKN1B CDKN2A CDKN2B CDKN2C CHEK1 CHEK2 CREBBP CRKL CRLF2 CSF1R CTCF CTLA4 CTNNB1 CUL3 CYP19A1 CYP1A1 CYP1A2 CYP1B1 CYP2A4 CYP2A6 CYP2B6 CYP2E1 DAXX DAZ1 DDR2 DICER1 DIS3 DNMT1 DNMT3A DNMT3B DOT1L E2F3 EGFL7 EML4 EP300 EPCAM EPHA3 EPHA5 EPHB1 ERBB2 ERBB3 ERBB4 ERCC2 ERCC3 ERCC4 ERCC5 ERG ESR1 ETV1 ETV6 EWSR1 EZH2 FAM123B FANCA FANCC FAT1 FBXW7 FGF19 FGF3 FGF4 FGFR1 FGFR2 FGFR3 FGFR4 FH FLCN FLT1 FLT3 FLT4 FOXA1 FOXL2 FOXP1 FUBP1 GATA1 GATA2 GATA3 GNA11 GNAQ GNAS GSK3B GSTA1 GSTP1 HGF HIF1A HIST1H3B HNF1A HRAS IDH1 IDH2 IFNGR1 IGF1 IGF1R IGF2 IKBKE IKZF1 IL10 IL7R INSR IRF4 IRS1 IRS2 JAK1 JAK2 JAK3 JUN KDM5A KDM5C KDM5D KDM6A KDR KEAP1 KIT KLF4 KRAS LATS1 LATS2 LMO1 MAP2K1 MAP2K2 MAP2K4 MAP3K1 MAP3K13 MAPK1 MAX MCL1 MDC1 MDM2 MDM4 MED12 MEF2B MEN1 MITF MLH1 MLL MLL2 MLL3 MPL MSH2 MSH6 MTHFD1 MTHFD1L MTHFR MTOR MUTYH MYC MYCL1 MYCN MYD88 MYOD1 NBN NCOR1 NF1 NF2 NFE2L2 NKX2-1 NKX3-1 NOTCH1 NOTCH2 NOTCH3 NOTCH4 NPM1 NR1I2 NRAS NSD1 NTRK1 NTRK2 NTRK3 NUTM1 PAK1 PAK7 PALB2 PARK2 PARP1 PAX5 PAX8 PBRM1 PDCD1 PDGFRA PDGFRB PDPK1 PGR PIK3C2G PIK3C3 PIK3CA PIK3CB PIK3CD PIK3CG PIK3R1 PIK3R2 PIK3R3 PIM1 PLK2 PMAIP1 PMS1 PMS2 PNRC1 POLE PPP2R1A PRDM1 PRKAR1A PRKY PTCH1 PTEN PTPN11 RAC1 RAD50 RAD51 RAD51B RAD51C RAD51D RAD52 RAD54L RAF1 RARA RASA1 RB1 RECQL4 REL RET RFWD2 RHOA RICTOR RIT1 RNF43 ROS1 RPS4Y2 RPS6KA4 RPS6KB2 RPTOR RUNX1 RYBP SDHA SDHAF2 SDHB SDHC SDHD SETD2 SF3B1 SH2D1A SLC22A1 SMAD2 SMAD3 SMAD4 SMARCA4 SMARCB1 SMO SOCS1 SOX17 SOX2 SOX9 SPOP SRC SRY STAG2 STK11 STK40 SUFU SYK TBX3 TERT TET1 TET2 TGFBR1 TGFBR2 TMEM127 TMPRSS2 TNFAIP3 TNFRSF14 TOP1 TP53 TP63 TRAF7 TSC1 TSC2 TSHR TSPY4 TTTY23 TYMS U2AF1 USP9Y VHL WT1 XIAP XPO1 YAP1 YES1 ZFY FUSIONS (>99% Sensitivity) INSERTION/DELETIONS (INDELS) (>95% Sensitivity) AMPLIFICATIONS Ideal for aggressive/rare cancers and patients with no treatment options

24 PositiveSelect is India's # 1 Cancer Genomics Test Ideal for patients with aggressive cancers, rare cancers and who have exhausted all treatment options PositiveSelect can be done on blood and blocks PositiveSelect is India s # 1 Cancer Genomics test with every 8 out of 10 patients selecting it for deciding their treatment PositiveSelect uses NGS, which is the New Gold standard of Molecular Diagonostics PositiveSelect provides industry leading NGS coverage at 1000x. PositiveSelect gives a more complete and comprehensive solution for cancer patients. Corporate Office: 1st Floor Kohinoor City Mall, Gate No. 1, Kirol Road, Kurla West, Mumbai, Maharashtra, India Toll Free: Website: info@positivebioscience.com

Jocelyn Chapman, MD Division of Gynecologic Oncology. Julie S. Mak, MS, MSc Genetic Counselor Hereditary Cancer Clinic

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