HOW CAN THE NETEST HELP ME IN THE

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HOW CAN THE NETEST HELP ME IN THE MANAGEMENT OF NET DISEASE?

HOW CAN THE NETEST HELP ME IN THE MANAGEMENT OF NET DISEASE?

1. DO I HAVE A NET AND HOW ACCURATELY DOES THE NETest DIAGNOSE IT?

1. DO I HAVE A NET AND HOW ACCURATELY DOES THE NETest DIAGNOSE IT? Based upon a meta-analysis of 10 separate, independent, peer-reviewed, published studies >95% accurate Prof Kjell Oberg, Uppsala, Sweden Annals Oncology 2020

2. HOW EFFECTIVE IS THE NETest IN GEP-NENs? 98% sensitive Prof Jonathan Strosberg, Moffitt

2. HOW EFFECTIVE IS THE NETest IN GEP-NENs? 98% sensitive Prof Jonathan Strosberg, Moffitt Tampa Neuroendocrinology 2020 99% sensitive Dr Anna Malczewska, ENETS Center of Excellence Neuroendocrinology 2020 93% sensitive Dr Mark van Treijen, ENETS Center of Excellence Frontiers Endocrinology 2018

3. IS THE NETest EFFECTIVE IN BP-NENs? 94% sensitive Prof Pier Luigi Filosso, Turin,

3. IS THE NETest EFFECTIVE IN BP-NENs? 94% sensitive Prof Pier Luigi Filosso, Turin, Italy Eur J Cardio. Thoracic Surgery 2020 100% sensitive Dr Anna Malczewska, ENETS Center of Excellence Neuroendocrinology 2020 93% sensitive Prof Pier Luigi Filosso, Turin, Italy Eur J Cardio. Thoracic Surgery 2018

4. CAN THE NETEST IDENTIFY MICROMETASTATIC DISEASE ? A) Ileocecal Primary B) DOTA PET

4. CAN THE NETEST IDENTIFY MICROMETASTATIC DISEASE ? A) Ileocecal Primary B) DOTA PET NEGATIVE NETest identifies 2 -3 mm NET hepatic disease (micromets) not detectable by CT, MRI or the NETspot Random Liver Biopsy +ve Dr Anna Malczewska, Prof Kos Kudla ENETS Center of Excellence J Clin. Endocrinol Metabolism 2020

B. HOW DOES THE NETest COMPARE TO OTHER BIOMARKERS? NETest = 99%; Cg. A

B. HOW DOES THE NETest COMPARE TO OTHER BIOMARKERS? NETest = 99%; Cg. A = 36% Dr Anna Malczewska, ENETS Center of Excellence Neuroendocrinology 2020 NETest = 93%; Cg. A = 56% Dr Mark van Treijen, ENETS Center of Excellence Frontiers Endocrinology 2018 NETest = 96%, Cg. A = 50% Dr Eric Liu, Rocky Mountain Cancer Center The Oncologist 2019

C. HOW THE NETest DETERMINES THE SUCCESS OF SURGERY AND IDENTIFIES RESIDUAL DISEASE? Blood

C. HOW THE NETest DETERMINES THE SUCCESS OF SURGERY AND IDENTIFIES RESIDUAL DISEASE? Blood NETest scores accurately identified Small intestine NENs. Curative surgery significantly decreased NETest scores. Monitoring NETest post-operatively facilitates management by early identification of residual/progressive disease. Dr Faidon Laskaratos, Royal Free*, London Endocrine 2020 The NETest is an accurate diagnostic biomarker for Pan. NETs (100%). A decrease in NETest levels after radical resection demonstrates the blood test provides early assessment of surgical efficacy. Cg. A had no clinical utility. Dr Stefano Partelli, San Rafaelle*, Milan Annals Surgical Ongology 2020 *ENETS Surgical Centers of Excellence

D. CAN THE NETEST IDENTIFY IF MY DISEASE IS PROGRESSING? The NETest® reliably predicted

D. CAN THE NETEST IDENTIFY IF MY DISEASE IS PROGRESSING? The NETest® reliably predicted stable disease and was the strongest predictor of progressive disease. Cg. A had lower utility. The NETest® anticipates RECIST defined disease status up to one year before imaging alterations are apparent. Dr Mark van Treijen, Utrecht*, Netherlands Neuroendocrinology 2020 High NETest correlated with progressive disease (81%; median PFS, 6 months). Low NETest correlated with stable disease (87%; median PFS, not reached). NETest is an accurate diagnostic and can be of use in monitoring disease status and facilitating management change in both watch-and-wait and treatment cohorts. *ENETS Center of Excellence Dr Eric Liu, Rocky Mountain Cancer Center The Oncologist 2019

E. CAN THE NETest TELL ME IF MY SSAs ARE EFFECTIVE? • In the

E. CAN THE NETest TELL ME IF MY SSAs ARE EFFECTIVE? • In the somatostatin analogue treated cohort, all low NETest patients (100%) remained stable. • A high NETest was linked to intervention and treatment stabilization (100%). • Use of NETest was associated with reduced imaging (biannual to annual) in 36%-38% of patients. The NETest is an accurate measure of SSA effectiveness and reduces the number of scans required Dr Eric Liu, Rocky Mountain Cancer Center The Oncologist 2019

F. CAN THE NETest PREDICT IF PRRT WILL BE EFFECTIVE? • The PPQ (PRRT

F. CAN THE NETest PREDICT IF PRRT WILL BE EFFECTIVE? • The PPQ (PRRT Predictive Quotient) is calculated using NET specific genes and tumor grade. • Measurement prior to therapy predicts PRRT efficacy, with an accuracy of 95%. Dr Lisa Bodei, Memorial Sloan Kettering Cancer Center Eur J Nuc Med Mol Imaging 2018

G. CAN THE NETEST DEMONSTRATE PRRT IS EFFECTIVE? • NETest accurately monitors PRRT response.

G. CAN THE NETEST DEMONSTRATE PRRT IS EFFECTIVE? • NETest accurately monitors PRRT response. It is as effective as imaging and has no radiation exposure. • NETest decrease identified responders and correlated (> 97%) with the pretreatment PPQ response predictor. • Cg. A was non-informative. Dr Lisa Bodei, Memorial Sloan Kettering Cancer Center Eur J Nuc Med Mol Imaging 2020

H. ARE THERE INDEPENDENT VALIDATION STUDIES? Prof Kjell Oberg, Uppsala, Sweden Annals Oncology 2020

H. ARE THERE INDEPENDENT VALIDATION STUDIES? Prof Kjell Oberg, Uppsala, Sweden Annals Oncology 2020 Meta-analysis 10 studies Dr. Mark van Treijen, ENETS Co. E Neuroendocrinology 2020 152 GEP-NETs (3 -5 years follow-up) Dr. Mark van Treijen, ENETS Co. E Prof Gerlof Valk, Utrecht Frontiers Endocrinol 2018 140 GEP-NETs, 113 controls Prof Jonathan Strosberg, Moffitt Neuroendocrinology 2020 96 patients and controls Dr. Anna Malczewska, ENETS Co. E Neuroendocrinology 2020 565 patients and controls Dr. Eric Liu, Rocky Mountain CC The Oncologist 2019 100 NETs (1 -2 years follow-up. I Prof Massimo Falconi ENETS Co. E – Milan Annals Surg Oncol 2002 30 PNET surgeries Dr. Lisa Bodei, MSKCC EJNMMI 2018, 2019 PRRT/NETest 158 GEP-/BPNETs Dr. Faidon Laskaratos ENETS Co. E – Royal Free Endocrine 13 SINET surgeries Dr. Pier Filosso ENETS Co. E – Turin Eur J Cardio. T Surg 2020 302 BPNETs & controls