1. Personalised Medicine in practice in The Netherlands – a SME’s view T. Kievits Director Vitromics Healthcare Holding Former EuropaBio’s PM Topic Group leader

2. Dutch Prime Minister Mark Rutte performs a PamChip test Entrepreneurship in PM TRON May 21-22 Warsaw2

3. Systemic Issues in Health Care TRON May 21-22 Warsaw3 With health care cost substantial and rising...... Market access for higher priced “niche buster” products? Trusheim et al. Stratified medicine: strategic and economic implications of combining drugs and biomarkers. Nature Reviews|Drug discovery, volume 6 april 2007 287-293 Affordable healthcare & innovation (is the solidarity principle sustainable)? Kaiser Family Foundations calculations using data from the US Department of Health and Human Services, Agency for Health care Research and Quality, Medical Expenditury P anel Survey, Household Component 2009

4. ....and it is the era of imprecision medicine! TRON May 21-22 Warsaw4 J. Schork, Time for one-person trials, Nature volume 520, 30 April 2015, 609-611

5. SME opportunities for impact with personalised medicine? TRON May 21-22 Warsaw5 1.Used as basis for new therapy development Complex projects; long development times; many parties involved; regulatory & reimbursement hurdles; difficult market access; etc 2. Improving delivery of existing therapy Still many parties involved, but less; limited to diagnostic play, therapy already in the market and reimbursed X V Our choice

6. The start of our first clinical project - February 2012 Jose Baselga BOLERO-2 Everolimus in Postmenopausal Hormone-Receptor–Positive Advanced Breast Cancer (ClinicalTrials.gov number NCT00863655; Funded by Novartis)NCT00863655 - June 2012 Koos van der Hoeven: Idea for biomarker study to avoid overtreatment in this patient group - During 2013 Emiel Voest: representing the Center for Personalised Cancer Treatment (Oncology Collaboration of Hospitals) Wim van der Meeren from the Dutch health insurance company CZ Tim Kievits specialised in Personalised Medicine from Vitromics TRON May 21-22 Warsaw6

7. Responder “Currently: no test” “New: Drug response test” - Up to 40% overtreatment - Side effects & delay for potential better treatment. - At 18 million Euro cost, with substantial unneccesary side effects Study goal: find pathway biomarker (NGS & PamChip) to minimalise overtreatment Everolimus & Exemestane treatment Responder Non-Responder Non- responder Patients Afinitor/Exemestane non-responders Afinitor/Exemestane responders TRON May 21-22 Warsaw7

8. Sci Signal.Sci Signal. 2013 Apr 2;6(269) The scientific drunk and the lamppost: massive sequencing efforts in cancer discovery and treatment. Yaffe MB.Yaffe MB Innovation incorporated TRON May 21-22 Warsaw8

9. Public-private partnership addresses overtreatment issue in oncology Result: a three party contract could be announced in January 2014 and the clinical biomarker trial has been started “Dutch healthcare insurer CZ, the Center for Personalised Cancer Treatment (CPCT) and VitrOmics, a company specialised in personalised medicine, have started a joint project to address the overtreatment issue within a certain group of patients with breast cancer” “…. to provide therapy to this group much more selective than currently is done in practice” “…. outstanding in an area where innovation can be very difficult” “…. showcases the need for parties to act outside of their comfort zone…” TRON May 21-22 Warsaw9

10. Study characteristics Response and non-response are well defined, coupled to practice of stopping & changing treatment Total number of patients participating: 100 – 200 range Limited number of participating hospitals for high quality & lower cost Three phased biomarker investigation: open, blinded & prospective. Start is observational (as close to routine practice as possible) Aimed at stratification patients before the start of the therapy with “a chance” versus “a very low chance” of therapy benefit Use of fit for purpose (e.g. use very minute sample amounts) analytically adequately validated technology platforms TRON May 21-22 Warsaw10

11. CZ, CPCT and Vitromics win the Value Based Healthcare Award The project “Public-private partnership addresses overtreatment issue in oncology” from Dutch healthcare insurer CZ, the Center for Personalised Cancer Treatment (CPCT) and VitrOmics, a company specialized in personalised medicine, is awarded one of three 2014 Value Based Healthcare Most Exceptional Initiative Awards. The Value Based Healthcare Prizes are awarded to recognize those projects that have adopted a fundamentally new line of thinking in creating value for patients in terms of real outcomes, real cost, real connections and one common language, and are patient-centred doctor-led initiatives. Harvard University Professor Michael E. Porter is honorary chairman of the Prize, and STZ (Stichting Topklinische Ziekenhuizen) and Erasmus Medical Center are co-auspices to the Prize. TRON May 21-22 Warsaw 11

12. 2 e and 3rd study on the way 2nd study: Lung cancer (prepared for funding) - Limit chemo therapy 3rd study: Esophageal cancer (study is financed) - Reduce surgery provide patient with better care after successful radio-chemo therapy (~ 30% of the patients in CROSS protocol) 12TRON May 21-22 Warsaw www.lung.orgwww.lung.org lung-cancer-fact-sheet.html may 2015

13. Conclusions New personalised medicine approaches contribute to addressing overtreatment situations currently existing in healthcare SME role in bringing parties together on relevant trial topic: – Discuss trial performance and implementation – Create common understanding of issues – Preemt problems that can be encounterd during trial – Assure role of patients Urgency is high to address overtreatment in oncology and relative small biomarker studies can help in these situations TRON May 21-22 Warsaw13

14. Personalised Medicine in practice in The Netherlands – a SME’s view tkievits@Vitromics.com