LET THE NEXT TREATMENT BE THE RIGHT TREATMENT

Personalized Ewing’s Sarcoma Case

Patient History (10yo) Was diagnosed at age 6 (2009) with Ewing’s Sarcoma of the scapula with bilateral pulmonary metastases. EWS-FLI1 fusion gene rearrangement was confirmed Initial therapy consisted of high dose vincristine, doxorubicin and cyclophosphamide alternating with ifosfamide and etoposide Scapulectomy revealed predominantly viable residual tumor (2010) Consolidative whole lung-irradiation was followed by a completion of 6 cycles of maintenance therapy using irinotecan and temozolomide (2011) Recurrent pulmonary metastases were developed and resected following 7 cycles of cyclophosphamide and topotecan therapy (2012) Personalized Ewing’s Sarcoma Case Patient pulmonary tumor was resected on February 2012 and engrafted in immune- deficient mice in order to form a Personalized TumorGraft model Rapid disease progression occurred during continued treatment with cyclophosphamide and topotecan followed by further aggressive progression over one month during treatment on a phase I trial

TUMORGRAFT PATIENT FIRST ROUND EXPANSIONTREATMENT RECOVERY ENGRAFTMENTRESECTION SURGERY The TumorGraft Process Preserve cancer cell heterogeneity Retain supporting microenvironment Maintain Intrinsic Cross-Talk Superior Pre-Clinical Model for Translational Oncology Ultimate Model for Personalized Oncology

Patient Sample TumorGraft Personalized Ewing’s Sarcoma Case Group%TGI%TR Gemcitabine/Docetaxel/Pazopanib62n/a Gemcitabine/Docetaxel/Bevacizumab12264 Mithramycin An/a Pazopanib47n/a Gemcitabine0n/a

December 5, 2012 March 20, 2013 In December 2012 the patient commenced treatment with the combination of gemcitabine+docetaxel+bevacizumab Initially suffered from acral dermatitis (treated locally) Scans performed at 6 weeks demonstrated clear clinical benefit (PR) Treatment continued and further tumor reduction was observed for a duration of 9 months MetastasisDecember 5January 21% Reduction Left lung upper lobe2.1 x x Left lung lower lobe3.8 x x Left lung lower lobe3.8 x x Pleura / Pericardium2.6 x x Mediastinum node5.1 x x Personalized Ewing’s Sarcoma Case

37 patients Sarcoma Experience 11 failed to grow 6 haven't proceeded to study16 successful clinical correlations SOC drugs Off-label drugs Investigational drugs

Leiomyosarcoma 45yo male Case Previous TreatmentAvatar Treatment Response *gemcitabine/docetaxel *doxorubicin/ifosfamide *gemcitabine/docetaxel/bevacizumab (PR, 9M) *sorafenib/temozolomide (PR, 9M) Chondrosarcoma 50yo male *docetaxel/irinotecan/bevacizumab (PR, 9M) Liposarcoma 56yo male *CDK4 inhibitor *JAK2 inhibitor *ifosfamide (PR, 5M) *regorafenib (PR, 7M) Pleomorphic Undiff. 52yo female *docetaxel/gemcitabine *doxorubicin (CR, >17M) Ewing’s Sarcoma 9yo boy *vincristine/doxorubicin/cyclophosphamide *ifosfamide/etoposide *irinotecan/temozolomide *cyclophosphamide/topotecan *docetaxel/gemcitabine/bevacizumab (PR, 8M) Fibromyxoid Sarcoma 48yo male *gemcitabine *cyclophosphamide *doxorubicin *sorafenib *temozolomide/irinotecan (PR, >6M) Sarcoma Experience

Predictive Power of TumorGrafts 85 Drug Tests with Clinical Correlation >90% Accuracy Patient PositiveNegativeTotal TumorGraft Positive67673 Negative11112 Total Clinical Sensitivity 67/68 = 98.5% Clinical Specificity 11/16 = 68.8% PPV: 67/73 = 91.8% NPV: 11/12 = 91.7% ImplantationGrowthStudyTreatmentOutcome

Ovarian Validation Study – Target start December 2013 Sarcoma – Target start January 2014 GI – Unknown Primary (UK) – in development Lung Validation Study – in development Breast Validation Study – in development Phase II Trial Investigator-initiated Newly diagnosed patients First line therapy Standard cytotoxic Monotherapy and combination Primary objective – response rate Secondary objective - PFS Clinical Validation studies Doxorubicin Ifosfamide Doxorubicin + Ifosfamide Gemcitabine + Docetaxel