LET THE NEXT TREATMENTBE 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

TU

MO

RG

RA

FT

PAT

IEN

TFIRST ROUND

EXPANSION TREATMENT

RECOVERY

ENGRAFTMENTRESECTION

SURGERY

The TumorGraft Process

Preserve cancer cell heterogeneityRetain supporting microenvironment

Maintain Intrinsic Cross-Talk

Superior Pre-Clinical Model for Translational OncologyUltimate Model for Personalized Oncology

0 4 6 9 13 16 20 23 27 30 34 410

200

400

600

800

1000

1200

1400

1600

1800

2000 ControlGemcitabine/Docetaxel/PazopanibMithramycin APazopanibGemcitabineGemcitabine/Docetaxel/Be-vacizumab

Test Day

Tum

or V

olum

e (m

m3)

Patient Sample TumorGraft

Personalized Ewing’s Sarcoma Case

Group %TGI %TR

Gemcitabine/Docetaxel/Pazopanib 62 n/a

Gemcitabine/Docetaxel/Bevacizumab 122 64

Mithramycin A n/a n/a

Pazopanib 47 n/a

Gemcitabine 0 n/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

Metastasis December 5 January 21 % Reduction

Left lung upper lobe 2.1 x 1.3 1.8 x 1.2 21

Left lung lower lobe 3.8 x 2.8 2.9 x 1.8 51

Left lung lower lobe 3.8 x 3.1 2.9 x 1.9 53

Pleura / Pericardium 2.6 x 1.1 2.2 x 0.4 70

Mediastinum node 5.1 x 4.1 3.7 x 2.3 59

Personalized Ewing’s Sarcoma Case

37 patients

Sarcoma Experience

11 failed to grow

6 haven't proceeded to study16 successful clinical correlations

37

26

20

SOC drugs

Off-label drugs

Investigational drugs

Leiomyosarcoma

45yo male

Case Previous Treatment Avatar 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  

    Positive Negative Total

TumorGraftPositive 67 6 73

Negative 1 11 12

  Total 68 16 85

• 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

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