ISTVAN PETAK, MD, PHDFOUNDER, SCIENTIFIC DIRECTOR

TM

7,6 MILLION13,1 MILLION

1:4GLOBOCAN 2008, WHO

Growth factor

Growth Factor ReceptorTyrosin kinases

Nucleus

Mutant Gene

A

Faulty signal transduction protein

Cancer Cell Targeted drugDivision

Which are the drugable gene mutations?

USA

Dr. ISTVAN PETAK

Dr. RICHARD SCHWAB

SWISS

1995 => 2002Story of kps (2003)

Biomedical RESEARCHERS trained in the usa and swiss

Schwab Richárd, Peták István, Pintér Ferenc….Kopper László, Kéri György, Pap Ákos

J Clin Oncol. 2005 Oct 20;23(30):7736-8.

Story of kps (2004)First molecular diagnostics based targeted tHerapy of a LUNG CANCER

PATIENT

MOLECULAR DIAGNOSTIC LABORATORY

LCM (ZEISS-PALM)

100%MULTIPLEX

XS-dXtm

OPTIMIZEDDIRECT PCR

PATENTED TECHNOLOGY TO ANALYZE SMALL SAMPLES

28 db 56 db

EGFR EXON 21 L858R

Successful diagnostics in 84 cells

(italian patient)

Response to therapy

INTERNATIONAL EXPANSION WITH THE SUPPORT OF VENTURE CAPITAL INVESTMENT IN 2012

1% of all genes90% somatic mutations20% germline mutations 10% show both somatic and germline mutations

500,000 mutations in 460 cAncer genes

Symbol Name GeneID Chr Chr Band

Cancer Somatic Mut

Cancer Germline Mut Tumour Types (Somatic Mutations) Tumour Types (Germline Mutations) Cancer Syndrome

Tissue Type

Cancer Molecular Genetics Mutation Type Translocation Partner

AKT1 v-akt murine thymoma viral oncogene homolog 1 207 14 14q32.32 yes breast, colorectal, ovarian, NSCLC E Dom MisAKT2 v-akt murine thymoma viral oncogene homolog 2 208 19 19q13.1-q13.2 yes ovarian, pancreatic E Dom AALDH2 aldehyde dehydrogenase 2 family (mitochondrial) 217 12 12q24.2 yes leiomyoma M Dom T HMGA2ALK anaplastic lymphoma kinase (Ki-1) 238 2 2p23 yes yes ALCL, NSCLC, Neuroblastoma, Breast, Colon ccneuroblastoma Familial neuroblastomaL, E, M Dom T, Mis, A NPM1, TPM3, TFG, TPM4, ATIC, CLTC, MSN, ALO17, CARS, EML4APC adenomatous polyposis of the colon gene 324 5 5q21 yes yes colorectal, pancreatic, desmoid, hepatoblastoma, glioma, other CNScolorectal, pancreatic, desmoid, hepatoblastoma, glioma, other CNSAdenomatous polyposis coli; Turcot syndromeE, M, O Rec D, Mis, N, F, SATRX alpha thalassemia/mental retardation syndrome X-linked 546 X Xq21.1 yes Pancreatic neuroendocrine tumors E Rec Mis, F, NBRAF v-raf murine sarcoma viral oncogene homolog B1 673 7 7q34 yes melanoma, colorectal, papillary thyroid, borderline ov, Non small-cell lung cancer (NSCLC), cholangiocarcinoma, pilocytic astrocytomaE Dom Mis, T, O AKAP9, KIAA1549BRCA1 familial breast/ovarian cancer gene 1 672 17 17q21 yes yes ovarian breast, ovarian Hereditary breast/ovarian cancerE Rec D, Mis, N, F, SBRCA2 familial breast/ovarian cancer gene 2 675 13 13q12 yes yes breast, ovarian, pancreatic breast, ovarian, pancreatic, leukemia (FANCB, FANCD1)Hereditary breast/ovarian cancerL, E Rec D, Mis, N, F, SCDKN2A -p16(INK4a) cyclin-dependent kinase inhibitor 2A (p16(INK4a)) gene 1029 9 9p21 yes yes melanoma, multiple other tumour typesmelanoma, pancreatic Familial malignant melanomaL, E, M, O Rec D, Mis, N, F, SCDKN2A- p14ARF cyclin-dependent kinase inhibitor 2A-- p14ARF protein 1029 9 9p21 yes yes melanoma, multiple other tumour typesmelanoma, pancreatic Familial malignant melanomaL, E, M, O Rec D, SCTNNB1 catenin (cadherin-associated protein), beta 1 1499 3 3p22-p21.3 yes colorectal, cvarian, hepatoblastoma, others, pleomorphic salivary adenoma E, M, O Dom H, Mis, T PLAG1DAXX death-domain associated protein 1616 6 6p21.3 yes Pancreatic neuroendocrine tumors E Rec Mis, F, NEP300 300 kd E1A-Binding protein gene 2033 22 22q13 yes colorectal, breast, pancreatic, AML, ALL, DLBCL L, E Rec T, N, F, Mis, O MLL, RUNXBP2ERBB2 v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian)2064 17 17q21.1 yes breast, ovarian, other tumour types, NSCLC, gastric E Dom A, Mis, OERCC2 excision repair cross-complementing rodent repair deficiency, complementation group 2 (xeroderma pigmentosum D)2068 19 19q13.2-q13.3 yes skin basal cell, skin squamous cell, melanomaXeroderma pigmentosum (D)E Rec Mis, N, F, SERCC3 excision repair cross-complementing rodent repair deficiency, complementation group 3 (xeroderma pigmentosum group B complementing)2071 2 2q21 yes skin basal cell, skin squamous cell, melanomaXeroderma pigmentosum (B)E Rec Mis, SERCC4 excision repair cross-complementing rodent repair deficiency, complementation group 42072 16 16p13.3-p13.13 yes skin basal cell, skin squamous cell, melanomaXeroderma pigmentosum (F)E Rec Mis, N, FERCC5 excision repair cross-complementing rodent repair deficiency, complementation group 5 (xeroderma pigmentosum, complementation group G (Cockayne syndrome))2073 13 13q33 yes skin basal cell, skin squamous cell, melanomaXeroderma pigmentosum (G)E Rec Mis, N, FFBXW7 F-box and WD-40 domain protein 7 (archipelago homolog, Drosophila)55294 4 4q31.3 yes colorectal, endometrial, T-ALL E, L Rec Mis, N, D, FFGFR2 fibroblast growth factor receptor 2 2263 10 10q26 yes gastric. NSCLC, endometrial E Dom MisIL6ST interleukin 6 signal transducer (gp130, oncostatin M receptor)3572 5 5q11 yes hepatocellular ca E Dom OKRAS v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homolog 3845 12 12p12.1 yes pancreatic, colorectal, lung, thyroid, AML, others L, E, M, O Dom MisMADH4 Homolog of Drosophila Mothers Against Decapentaplegic 4 gene4089 18 18q21.1 yes yes colorectal, pancreatic, small intestine gastrointestinal polyps Juvenile polyposis E Rec D, Mis, N, FMAP2K4 mitogen-activated protein kinase kinase 4 6416 17 17p11.2 yes pancreatic, breast, colorectal E Rec D, Mis, NMDM2 Mdm2 p53 binding protein homolog 4193 12 12q15 yes sarcoma, glioma, colorectal, other M, O, E, L Dom AMLH1 E.coli MutL homolog gene 4292 3 3p21.3 yes yes colorectal, endometrial, ovarian, CNScolorectal, endometrial, ovarian, CNS Hereditary non-polyposis colorectal cancer, Turcot syndromeE, O Rec D, Mis, N, F, SMSH2 mutS homolog 2 (E. coli) 4436 2 2p22-p21 yes yes colorectal, endometrial, ovarian colorectal, endometrial, ovarian Hereditary non-polyposis colorectal cancerE Rec D, Mis, N, F, SMSH6 mutS homolog 6 (E. coli) 2956 2 2p16 yes yes colorectal colorectal, endometrial, ovarian Hereditary non-polyposis colorectal cancerE Rec Mis, N, F, SMSI2 musashi homolog 2 (Drosophila) 124540 17 17q23.2 yes CML L Dom T HOXA9

460 cancer genes

SANGER DATABASE

2010. Október 6. 11. dia

Abbott Astra-Z GSK Lilly Merck Novartis Pfizer Roche Wyeth

EGFR x xVEGF/R x xIGF/R x x xcMET x x x xMulti x x x x x xPI3K/mTOR x x x x xRAF x x xMEK x xSRC x xCDK4/6 xCHK1 x xAurorakináz x x xEg5,kinezin xTubulin x xPARP x x xBCL2 xIAP xSurvivin xHSP90 x xDeacetiláz xEndotelin x x-szekretáz x xMDM2 xDKK1 x5-reduktáz xVDA x

TARGETED THERAPIES IN PIPELINES

5000< CLINICAL TRIALS FOR BREAST CANCER (WWW.CLINICALTRIALS.GOV)

MORE AND MORE BIOMARKER DRIVEN LOOKING FOR SMALL FRACTION OF PATIENTS

MOLECULAR TARGETS 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 …50

CLIN

ICAL

PAR

AMET

ERS

1

2

3

4

5

6

7

8

9

1

0 …

.

A

B

CPIONEERING NEXT GENERATION SEQUENCING IN ONCOLOGY

„HeurAA” Heuristic Amplicon Analyzer

PATENTED TECHNOLOGY TO find mutations IN MANY SEQUENCES

Number of genesnu

mbe

r

2009 2010 2011 2012

58 genesABL1, AKT1, ALK, APC, ATM, BRAF, CDH1, CDKN2A, CSF1R, CTNNB1, EGFR, ERBB2, ERBB4, FBXW7, FGFR1, FGFR2, FGFR3, FLT3, GNAS, HNF1A, HRAS, IDH1, JAK2, JAK3, KDR, KIT, KRAS, MET, MLH1, MPL, NOTCH1, NPM1, NRAS, PDGFRA, PIK3CA, PTEN, PTPN11, RB1, RET, SMAD4, SMARCB1, SMO, SRC, STK11, TP53, VHL.+ egyedi gének+FISH: EGFR, HER-2, FGFR, ALK, MET

TARGETED RESEQUENCING PANELS

Illumina HiSeq™ 2000 platform for 2574 exons representing 176 genes captured using Agilent SureSelect™

50% acionable mutations

MGH's Diagnostic Molecular Pathology lab

SNaPshot assay, hotspot mutations in 14 oncogenes

50 to 60 patients per week

NEXT: NGS 50 different targets

Genomweb September 19, 2012+in combination with fluorescence in situ hybridization

MOLECULAR GENETICS BASED PERSONALIZED SIGNAL TRANSDUCTION THERAPIES

GENE TEST

CANCER CELLS

58< TARGET

280<TARGETED DRUGS

ONCOMPASS TM IS A “BLUE OCEAN” SERVICE IN A RAPIDLY GROWING MARKET

OUR COSTUMERS:

PATIENTS: THEY WANT ACCESS TO MORE EFFECTIVE AND LESS TOXIC TARGETED THERAPY

PHARMA: THEY WANT TO FIND PATIENTS WITH RARE GENETIC PROFILE MATCHING THEIR DRUG

PHARMA/CRO: THEY WANT TO RECRUIT PATIENTS WITH RARE GENETIC PROFILE TO ACCELERATE

DOCTORS/HOSPITALS: THEY WANT MORE PATIENTS, CLINICAL TRIALS ARE PROFITABLE AND COMPETITIVE

PAYERS/INSURANCE: THEY WANT MORE COST EFFECTIVE TREATMENT, THEY WANT MORE PATIENTS IN CLINICAL TRIALS

ONCOMPASS TM IS A “BLUE OCEAN” SERVICE IN A RAPIDLY GROWING MARKET IN THE NEXT 20 YEARS

ENGINES OF GROWTH:

PATIENTS: THE NUMBER WILL 2X IN THE NEXT 20 YEARS (INCREASE WILL BE FASTER IN ASIA)

DRUGS: THE NUMBER OF TARGETED DRUGS WILL 10X

GENES: NUMBER OF GENES ANALYZED ON ONE CHIP WILL 10X

THANK YOU FOR YOUR KIND ATTENTION!