FOUNDER, SCIENTIFIC DIRECTOR TM ISTVAN PETAK, MD, PHD FOUNDER, SCIENTIFIC DIRECTOR

7,6 MILLION 13,1 MILLION 1:4 GLOBOCAN 2008, WHO

Which are the drugable gene mutations? Growth factor Growth Factor Receptor Tyrosin kinases A Mutant Gene Census Nucleus Faulty signal transduction protein Cancer Cell Targeted drug Division

Biomedical RESEARCHERS trained in the usa and swiss Story of kps (2003) Biomedical RESEARCHERS trained in the usa and swiss 1995 => 2002 Dr. ISTVAN PETAK USA Dr. RICHARD SCHWAB SWISS

Story of kps (2004) First molecular diagnostics based targeted tHerapy of a LUNG CANCER PATIENT 2003 2004 2009 Schwab Richárd, Peták István, Pintér Ferenc….Kopper László, Kéri György, Pap Ákos J Clin Oncol. 2005 Oct 20;23(30):7736-8.

MOLECULAR DIAGNOSTIC LABORATORY

PATENTED TECHNOLOGY TO ANALYZE SMALL SAMPLES 100% MULTIPLEX XS-dXtm OPTIMIZED DIRECT PCR LCM (ZEISS-PALM)

Successful diagnostics in 84 cells (italian patient) 28 db 56 db EGFR EXON 21 L858R Response to therapy

INTERNATIONAL EXPANSION WITH THE SUPPORT OF VENTURE CAPITAL INVESTMENT IN 2012

500,000 mutations in 460 cAncer genes SANGER DATABASE 460 cancer genes 1% of all genes 90% somatic mutations 20% germline mutations 10% show both somatic and germline mutations

TARGETED THERAPIES IN PIPELINES Abbott Astra-Z GSK Lilly Merck Novartis Pfizer Roche Wyeth EGFR x x VEGF/R x x IGF/R x x x cMET x x x x Multi x x x x x x PI3K/mTOR x x x x x RAF x x x MEK x x SRC x x CDK4/6 x CHK1 x x Aurorakináz x x x Eg5,kinezin x Tubulin x x PARP x x x BCL2 x IAP x Survivin x HSP90 x x Deacetiláz x Endotelin x x g-szekretáz x x MDM2 x DKK1 x 5a-reduktáz x VDA x Bali 2010. Október 6. 11. dia 11

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 1 2 3 4 5 6 7 8 9 10 …. CLINICAL PARAMETERS

PIONEERING NEXT GENERATION SEQUENCING IN ONCOLOGY

„HeurAA” Heuristic Amplicon Analyzer PATENTED TECHNOLOGY TO find mutations IN MANY SEQUENCES „HeurAA” Heuristic Amplicon Analyzer

Number of genes number 2009 2010 2011 2012

TARGETED RESEQUENCING PANELS 58 genes ABL1, 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 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 Feri Dia next gen Messechusec 15 gén átállás Ilimuna, roche, Foundation med, diagnostics

MOLECULAR GENETICS BASED PERSONALIZED SIGNAL TRANSDUCTION THERAPIES GENE TEST 58< TARGET 280< TARGETED DRUGS CANCER CELLS

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!