What is the current status on clinical trials in Belgium and how are we positioned globally?

1. What is the current status on clinical trials in Belgium and how are we positioned globally?

2. The presentation will give you insights on the current Belgian situation and how we are positioned globally Deloitte • Methodology: analysis of the database of clinical trial applications (CTA’s)of the Federal Agency for Medicines and Health Products (FAGG/AFMPS) • Studyperiod:all clinical trials submitted to the FAGG/AFMPS between 2006and mid 2009 MDCPartners • Methodology: Semantic web mining and disambiguation of public disclosures • Study period:the analysis was extracted from data between 2006 and 2009

3. Belgium has a long and important tradition in clinical trials • The pharmaceutical industry in Belgium takes 40% of the private investments in R&D on their account • Belgium has the highest number of medicines under development per capita • 9% of all clinical trials in Western Europe are performed in Belgium • High availability of skilled research staff, excellent infrastructure, the proximity of knowledge centers and suppliers,… • In 2007, Belgium was ranked as best country in the world for academic research, according to scientific journal The Scientist The Belgian pharmaceutical sector has a leading role in the achievement of the R&D investment targets which the EU member states set themselves as part of the Lisbon Strategy.

4. Yet, this position is under siege… Less expensive E.g. a trial for a standard drug in the US can cost up to $150 million. A similar drug could be tested in India for less than half of that amount. • Currently the majority of clinical trials is still conducted in Western countries • However, the number of trials performed in emerging countries is increasing quickly. • E.g. the number of clinical trials initiated in Central and Eastern Europe more than tripled from 2002 to 2007 • Clinical trials with innovative drugs should remain in Western countries Availability of large patient populations EMERGING COUNTRIES E.g. India: genetically diverse, drug-naive population of over a billion people Reformation of rules & legislations E.g. India: reformation of regulatory approval in 2006 India will automatically accept certain protocols if approved in the recognized countries

5. Strategic Move – Expand Market size through increased focus on Emerging Markets Attractions Challenges • Complex business environment • Insufficient IP protection • Tight control of drug prices • Low level of reimbursement and public • funding of health provision • Growing economy, high out-of-pocket • expenditure on drugs • Blooming middle class’s preference • for branded drugs • Improving regulatory and • IP environment • Growing prevalence of western • types of diseases • Large population

6. But the percentage of Trials shifting to Emerging teritories is stillnegligable Figure1: Evolution of trials per year per country

7. European Enrollment (oncology, CNS, Diabetes, Pain, Arthritis) UK NL D F B

8. China in perspective UK NL D China F

9. What a wonderful world (diabetes 2009)

10. Academic ranking for Belgium and neighbouring countries

11. The number of submitted and accepted trials in Belgium has increased Figure2: Number of submitted and accepted trials at the FAGG/AFMPS Source: Federal Agency for Medicines and Health Products (FAGG/AFMPS) • An increase has been observed in clinical trial applications over the first 3 years • In 2009 the number of trials decreased strongly and is back on the level of 2006. • Overall the acceptance rate of the FAGG/AFMPS is high and varies between 80.8% and 92.7%

12. The same trend is observedforemergingcountries (only CNS and cancer) Figure3: Number of submitted trials in Emerging countries Source: MDCPartners • An increase in all countries has been observed in clinical trial applications over the first 3 years where after a decrease is observed • China is the exception, the increase in number of clinical trials is continued in 2009

13. Most of clinical research in Belgium is performed in Phase III Figure 4: Percentage of industry sponsored and academic trials per phase (2006 to Sem. 1 2009) Source: Federal Agency for Medicines and Health Products (FAGG/AFMPS) • Most of the clinical research in Belgium is performed in Phase III (=37.0%). Phase IV (=10.4%) research is the least performed • More than 50% of all clinical trial activity happens in early phase research (Phases I and II). • Industry sponsored research in Belgium is mainly focused on pre-launch studies • Only for Phase IV research, the percentage of industry sponsored and academic trials is relatively similar • Phase I research is the least sponsored by academia

14. Industry sponsored trials constitute the majority of trials in all countries Figure 5: Percentage of industry sponsored and academic trials in Belgium and neighboring countries Source: Federal Agency for Medicines and Health Products (FAGG/AFMPS) • In Belgium the number of non-commercial trials is rather low compared to other EU member states, while the Belgian legislation is rather positive for academic trials. • The highest percentage of academic trials is seen in Germany with 37.3% all trials. The lowest percentage is seen in Belgium with 14.3%

15. 5 academic institutions in Belgium account for 69.7% of initiated trials Figure 7: Total percentage of trials per phase for top 5 academic institutions (2006 to Sem.1 2009) EORTC* 7.2% 16.5% • EORTC 11.5% Erasme 10.1% 10.7% 5.4% 7.7% 16.9% 4.1% UCL12.7% 17.5% 15.4% 6.2% 12.2% UZ Gent18.3% 15.4% 11.5% 24.3% KULeuven24.1% 12.3% 19.2% 35.0% 9.5% 7.7% *EORTC= European Organization for Research and Treatment of Cancer Source: Federal Agency for Medicines and Health Products (FAGG/AFMPS) • Of all newly initiated academic clinical trials per phase, the top 5 institutions represent 79.6% of all PhaseIV research, followed by Phase I (65.4%), Phase III (58.5%) and Phase II (55.4%) • Very high contribution of the top 5 academic institutions compared to the share of the top 5 industrycompanies

16. Belgian clinical institutions are performing well internationally Figure 6: Top organizations near country analysis in the indication of Pain Leuven Gent Liege VUB UCL ULB Antwerp Source: MDCPartners

17. In Belgium the top 5 companies account for 40.9% of initiated industry trials Figure 8: Total percentage of trials per phase for top 5 companies (2006 to Sem.1 2009) 3.7% 14.6% 4.3% 5.2% 2.2% 3.4% 7.1% 9.7% 4.7% 15.1% 6.8% 7.1% 2.4% 1.4% 9.7% 8.7% 9.2% 8.8% 6.3% 19.7% 4.7% 16.1% 11.7% 7.9% 7.4% Source: Federal Agency for Medicines and Health Products (FAGG/AFMPS) • For all Phase I trials initiated by pharmaceutical companies, the top 5 companies have an important shareequaling 56.5% • The top 5 companies account for 41.9% of all industry sponsored Phase IV research and 30.0% and 29.1%of Phase III and Phase II research respectively

18. Almost 1 out of 4 clinical trials target cancer research Figure9: Percentage of newly started clinical trials per indication (2006 to Sem. 1 2009) Genito and urinary system Other Other Respiratory system Musculo-skeletal system *Phase I research (all therapeutic domains) is reported separately due to the specificity and importance Source: Federal Agency for Medicines and Health Products (FAGG/AFMPS) • Cancer research is followed in order of importance by trials in the Alimentary tract and metabolism system (7.9%), Nervous system (7.8%) and Cardiovascular system (7.3%)

19. Belgium is doing well in attracting oncology trial work Figure 10: 3.7% EU Avg. 9.7% Belgium .4% 6.3% 19.7% 16.1% 11.7% 7.4% Source: MDCpartners The average therapeutic spread is in line with the global and EU in the area of oncology Belgium is 10% above the EU average

20. The number of publications in Belgium is low compared to neighboring countries Figure12: Number of publicationsononcology Figure11: Number of trials in oncology Figure14: Number of publications on CNS Figure13: Number of trials in CNS Source: MDCPartners • Although the relative similar number of trials in oncology in Belgium and the Netherlands it is observed that the number of publications is much higher in the Netherlands

21. Most clinical research in Belgium is performed in adults Figure 14: Percentage of initiated clinical trials per age group Source: Federal Agency for Medicines and Health Products (FAGG/AFMPS) • The results show clearly that most research is performed in adults followed by the elderly • The percentage of trials per age group remainsstable in 2008 • During the first semester of 2009 a trend towards more research in children (=15.8%) is observed

22. On average, 39 patients are to be recruited for a clinical trial in Belgium Figure 15: Average number (N) of patients to be recruited per trial type and share (%) of global to be recruited patients Source: Federal Agency for Medicines and Health Products (FAGG/AFMPS) • The least patients are needed for phase I and phase II research (approximately 28 patients) whereas for phase IV research most patients are needed (=63.7). On average 39.2 patients are needed per trial • The average number of patients to be recruited for academic trials (=60.1) is much higher compared to industry sponsored trials (=32.2) • The share of Belgian patients to be recruited for all trials initiated in Belgium equals 5.9%

23. The target number of patients to be recruited for Phase II research is high Figure 16: Relative number to be recruited (per 100,000) patients for phase II research (2006 to 2009) 31.5 Source: MDCPartners • Belgium has the highest relative number (N=31.5) of to be recruited patients for Phase II research • At 12.2 France has the lowest in phase ll

24. Conclusions • Between 2006 and 2008, an increase in the number of clinical trial applications was observed in all countries. In 2009 a substantial decrease in applications is observed. A possible explanation could be the economic crisis • Most of trials in Belgium are performed in Phase III (=37.0%). Phase IV (=10.4%) research is the least performed in Belgium. More than 50% of all clinical trial activity happens in early phase research (Phases I and II) • The share of academic trials is low compared to neighboring countries • Most clinical trials target cancer research (23.7%) followed by trials in the alimentary tract and metabolism system (7.9%), nervous system (7.8%) and cardiovascular system (7.3%) • Compared to the neighboring countries Belgian investigators have few articles although they are very well positioned internationally • Globally The number of participating sites have decreased strongly since 2005

25. Discussion Globally operating companies will buy in technologies/concepts for new drugs from small private entrepreneurs and the academic world. Product development will be coordinated by these global players. Major activities will be outsourced to specialized companies. Quality of the work and speed will be decisive success factors. • The classical high risk/high gain business model of innovative pharmaceutical companies may not be the best way forward for the industry. May lead to: – more lean companies – increasing partnering with other specialized companies, research organizations/institutions at various stages of drug development. – more public-private-partnerships

26. Discussion • Regulatory authorities will be more transparent in their decision-making process, and global harmonization will grow. • • Future therapeutic interventions will use new tools provided by a new enabling technologies. • The paradigm of individualized medicine will be accepted as standard in many therapeutic fields, and the borderlines between diagnostics, drugs and medical devices will blur. • • Countries like India and China will become important global pharmaceutical players and users by 2020

27. Q&A Thank you for your attention