This document discusses the importance of clinical trials for developing new medicines and treatments. It notes that clinical trials contribute to scientific advances in areas like cancer genomics and new drug technologies. However, clinical trial activity has been lower in Greece compared to similar EU countries due to inadequate regulatory and administrative support. The document advocates for partnerships between government and industry to improve the clinical trial environment and facilitate access to innovative medicines. It outlines Roche's investments in clinical trials and new cancer treatments in Greece.

1. Κλινική Έρευνα … στην πράξη!
Χρήστος Αντωνόπουλος MD, Ph.D.
Ιατρικός Διευθυντής
Ιατρικό Τμήμα
Roche Hellas

2. “Clinical trials are crucial for developing new
medicines, improving existing treatments,
boost research and
contribute to economic growth”
2
John Dalli, former EU Health Commissioner

3. Proprietary and confidential. For internal use only.
3
Advances in science
Scientific
Knowledge
Advances in
Technology
Integrated
Development
Antibody-drug conjugate
Cancer genomics MET IHC
Drugs +
Biomarkers &
Diagnostics
Glyco-engineered antibody
Dual acting fragment antibody
Bi-specific antibody

4. Proprietary and confidential. For internal use only.
4

5. Proprietary and confidential. For internal use only.
Baseline
aPDL1 Phase I Study
23% Response Rate in NSCLC
Post C2 (Week 6)
Herbst et al ASCO 2013

6. Proprietary and confidential. For internal use only.
6
Advances in science
Scientific
Knowledge
Advances in
Technology
Integrated
Development
Antibody-drug conjugate
Cancer genomics MET IHC
How can society leverage this progress?
Drugs +
Biomarkers &
Diagnostics
Glyco-engineered antibody
Dual acting fragment antibody
Bi-specific antibody

7. Government and industry roles in R&D
Should complement each other in partnership
“Partnerships benefit both industry
and academia by providing
opportunities for the sectors to work
together to explore promising new
technologies and address scientific
problems that may lead to
breakthroughs in treatments for the
most challenging diseases and
conditions”.
Tufts Center for the Study of Drug Development
7
Pharmaceutical Industry
National Health System

8. Clinical trial activity in Greece
Significantly less vs. similar size EU countries
Clinical trials submitted in MAAs to EMA**
8
Even before crisis, Greece spend
little on RD in terms of % of GDP
– 0.6% in 2007 vs. 1.8% UK or
3.7% in Finland*
Since crisis, significant reduction of
government funding of ~50%*
Pharmaceutical industry maintained
investment in RD despite difficult
environment
3
x2
x
Source: *Malone, J, “Greek science: hope in crisis; Lancet 2012 **Clinical trials submitted in marketing-authorization applications
to the European Medicines Agency 2005-2011

9. Clinical trial enironment in Greece
Cautious optimism, outlook improving
Good quality infrastructure….
Sufficiently large patient pool
(11m population)
~130 public public hospitals
7 medical schools
Highest number of physicians
per capita
...limited by inadequate processes
and lack of support for CTs
Regulatory framework
Administrative procedures
Complexity of approval processes
Lack of acknowledgment of clinical
trials as investment priority
Source: Athanasakis et al., National School of Public Health, Archives of Hellenic Medicines, 2012 9

10. How to improve environment for CTs in Greece
Create more favorable environment for RD investment
Rapid access to
innovative
medicines
Sustainable,
balanced
Budget
Revised
Claw Back
Mechanism
Respect for
Intellectual
Property
Rights
Predictability
and
Transparency
Payment of
outstanding
Debts

11. Roche investing in Greece
Significant investment, increased in 2014
Investment in
Clinical Trials
Bringing
Innovative
Medicines to
Greece
Collaborations
with local
partners
Management
Trainee Program
Uninsured
Patients
Support
Program
CSR initiatives

12. Roche investing in Greece
Continue to heavily invest in clinical trials
Clinical Trials
Growth is closely
linked with clinical
research
investments.
31 clinical trials
in 170 centres
including 1200
patients
Bringing
Innovative
Medicines to
Greece
Novel treatments
for Cancer
combining
medicines with
diagnostics =
Personalized
Healthcare

13. CLEOPATRA Study Design
HER2-positive MBC
centrally confirmed
(N = 808)
Placebo + trastuzumab
1:1
Docetaxel*
≥ 6 cycles
n = 406
n = 402
Pertuzumab + trastuzumab
Docetaxel*
≥ 6 cycles
PD
PD
• Randomization stratified by geographic region and
* 6 cycles allowed for unacceptable toxicity or PD; 6 cycles allowed at investigator discretion. 13
HER2, human epidermal growth factor receptor 2;
MBC, metastatic breast cancer;
Baselga J, et al. N Engl J Med 2012; 366:109–119.
PD, progressive disease.
neo/adjuvant chemotherapy
• Study dosing q3w:
– Pertuzumab/placebo: 840 mg loading → 420 mg maintenance
– Trastuzumab: 8 mg/kg loading → 6 mg/kg maintenance
– Docetaxel: 75 mg/m2 → 100 mg/m2 escalation if tolerated

14. Final OS Analysis
Median follow-up 50 months (range 0–70 months)
14
OS (%)
100
90
80
70
60
50
40
30
20
10
0
HR 0.68
95% CI = 0.56, 0.84
p = 0.0002
Ptz + T + D
Pla + T + D
40.8
months
56.5
months
Δ 15.7
months
0 10 20 30 40 50 60 70
371 318 268 226 104 28 1
350 289 230 179 91 23 0
n at risk
Ptz + T + D
Pla + T + D
402
406
ITT population. Stratified by geographic region and neo/adjuvant chemotherapy.
CI, confidence interval; Pla, placebo; Ptz, pertuzumab.
Time (months)
ESMO 2014
S. Swain et al. Final overall survival (OS) analysis from the CLEOPATRA study of first-line (1L) pertuzumab (Ptz), trastuzumab (T), and docetaxel (D) in patients (pts)
with HER2-positive metastatic breast cancer (MBC). Presidential Symposium 1.ESMO 2014.Abstract number 350O_PR 14

15. Proprietary and confidential. For internal use only.
Multiple Sclerosis
Over 2.3M people affected worldwide
• Chronic autoimmune disease; damages
the brain spinal cord
• Demyelination, axonal (nerve fiber)
injury and scarring
• Variable clinical course: 4 main patterns
• Treatment: interferon, disease modifying
agents
• Median age 23 years; ~2:1 female
• Second leading cause of acquired
neurologic disability in young adults:
• Visual loss
• Sensory and motor symptoms
• Loss of coordination
• Bladder/bowel dysfunction
1MSIF, Atlas of MS 2013, http://www.msif.org/includes/documents/ cm_docs/2013/m/msif-atlas-of-ms-2013-report.pdf?f=1

16. Proprietary and confidential. For internal use only.
Geographic Atrophy (GA)
Advanced form of dry Age-related Macular Degeneration
Advanced form of dry Age-related Macular Degeneration
● Progressive, degenerative disease
of the central retina (macula)
● Interferes with driving, reading,
watching TV,
daily living
● Accounts for ~10% legal blindness
● Affects 8M people WW, ~1.2M in
US
PROGRESSION of GEOGRAPHIC ATROPHY
No Currently Approved Standard Of Care
● Genetic predisposition: complement factor H
● Supports role of inflammation in etiology

17. Proprietary and confidential. For internal use only.
Clinical investigation of the amyloid hypothesis in Alzheimer’s Disease
Brain Amyloid Beta expression
Amyloid expression may
precede Alzheimer
symptoms by 20 years
Clinical symptoms
HYPOTHESIS:
Accumulation of amyloid
in brain drives Alzheimer
pathogenesis and leads
to neuronal dysfunction
and cognitive decline

18. Doing now what patients need next