LET THE NEXT TREATMENT BE THE RIGHT TREATMENT

1. LET THE NEXT TREATMENT BE THE RIGHT TREATMENT

2. Personalized Ewing’s Sarcoma Case

3. 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 • Scapulectomyrevealed 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) 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 topotecanfollowed by further aggressive progression over one month during treatment on a phase I trial

4. The TumorGraft Process SURGERY RECOVERY FIRST ROUND PATIENT TUMORGRAFT Preserve cancer cell heterogeneity Retain supporting microenvironment Maintain Intrinsic Cross-Talk Superior Pre-Clinical Model for Translational Oncology Ultimate Model for Personalized Oncology RESECTION ENGRAFTMENT EXPANSION TREATMENT

5. Personalized Ewing’s Sarcoma Case Patient Sample TumorGraft

6. Personalized Ewing’s Sarcoma Case • 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 December 5, 2012 March 20, 2013

7. Sarcoma Experience 37 patients 11 failed to grow 37 26 16 successful clinical correlations 6 haven't proceeded to study 20 SOC drugs Off-label drugs Investigational drugs

8. Sarcoma Experience Previous Treatment Avatar Treatment Case Response Leiomyosarcoma45yo male *gemcitabine/docetaxel*doxorubicin/ifosfamide *gemcitabine/docetaxel/bevacizumab (PR, 9M) *sorafenib/temozolomide (PR, 9M) *docetaxel/irinotecan/bevacizumab (PR, 9M) Chondrosarcoma 50yo male *ifosfamide (PR, 5M) *regorafenib (PR, 7M) Liposarcoma 56yo male *CDK4 inhibitor *JAK2 inhibitor PleomorphicUndiff.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) *gemcitabine *cyclophosphamide *doxorubicin *sorafenib Fibromyxoid Sarcoma 48yo male *temozolomide/irinotecan (PR, >6M)

9. Predictive Power of TumorGrafts 85 Drug Tests with Clinical Correlation >90% Accuracy • Clinical Sensitivity 67/68 = 98.5% • Clinical Specificity 11/16 = 68.8% • PPV: 67/73 = 91.8% • NPV: 11/12 = 91.7% Implantation Growth Study Treatment Outcome

10. Clinical Validation studies • 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 • Doxorubicin • Ifosfamide • Doxorubicin + Ifosfamide • Gemcitabine + Docetaxel

11. Thank You !!!