Slides from a presentation given at the Pistoia Alliance European Conference 2015, in Zurich, Switzerland.

1. Avicenna: A Strategy
for In Silico Clinical
Trials
Adriano Henney
Executive Director VPH Institute

2. Increasing ageing population
Prevalence of chronic debilitating diseases in
over 65s
Current therapies limited success
Increasing unmet medical need
Tendency for medicines to benefit smaller
proportion of patient population
increasing emphasis on “Personalised
Medicine”
Ability to deliver effective novel medicines to
market declining
costs escalating
increasing burden on healthcare
budgets
“A Perfect Storm” in 21st
Century Healthcare
2
Equates to growth from
3.5% to 8.5% GDP over
the same period

3. 3
PricewaterhouseCoopers Report
http://www.pwc. com/gx/en/pharma-life-sciences/pharma-2020/pharma-2020- vision-
path.jhtml.
“
”
•We believe that, if the industry is to
become more innovative and cut its
R&D costs, four features will be vital:
• A comprehensive understanding of how
the human body works at the molecular
level
• A much better grasp of the
pathophysiology of disease
• Greater use of new technologies to
“virtualise” the research process and
accelerate clinical development
• Greater collaboration between the
industry, academia, the regulators,
governments and healthcare providers.

4. What is Avicenna?
 Ab Al al- usayn ibn Abd All h ibn Al-Hasanū ʿ ī Ḥ ʿ ā
ibn Ali ibn S nī ā
 The Canon of Medicine 1025 AD
 In Silico Clinical Trials: How Computer
Simulation Will Transform The Biomedical
Industry
 An international research and development
roadmap for an industry-driven initiative
 EC funded Cooperation and Support Action

5. In silico clinical trials
• The use of patient-specific computer modelling
and simulation applied in the research and
development of new biomedical products, as
well as in their evaluation and assessment
• Both clinical and pre-clinical.
• From physiology-based pharmacokinetics to
collections of patient-specific dynamic models
• Quantitative data, including medical imaging
and sensing
• Dynamic system view

6. Not a “single hit” phenomenon
Arise from maladaptations
that reflect an alteration in the
state of a system
Driven by the reorganisation of
regulatory networks ->
defective system response
Correction requires
identification of key control
points focusing on
normalising system response
Complex Multifactorial Diseases
6

7. Complex Network Analytics
7
Statistics
Bioinformatics
‘Omics Data
Signatures, Profiles,
Associations, Inference
Signatures, Profiles,
Associations, Inference
Static ViewStatic View

8. Modelling & Simulation
8
Courtesy Prof Peter Sorger, Harvard Med Sch
NewSimulation
RefineModel
Verify Simulation
Verify Simulation
“Validated”
ModelModel
“Validated”
ModelModel
Dynamic not
Static
Dynamic not
Static

9. Community
of Practice
Avicenna: major objectives
Roadmap Industrial Alliance

10. Mapping the territory: a new ISCT industry
Merging two
existing sectors:
• Clinical trial industry
(provides design, execution
and interpretation of clinical
trials)
+
• Virtual Prototype
industry (provide in silico
design and assessment for
industrial sectors – aero-
space, nuclear…)

11. Objectives
• Stakeholder engagement
• Map processes -> CT
• Identify points of CM&S application
• Collect data from widest possible sources
• Acquire opinions on key themes
• Identify key areas & topics for action -> roadmap
• Achieved using AO process- Schellingpoint LLP
Opinion Surveys
Producers
Spenders
Providers
Consumers
Research
Regulators

12. CSA Structure
AO process -> collects/ analyses information to
input and review/process output

13. Alignment Cycles
gather and process the
four categories of
opinion that drive our
actions and inaction
Alignment Cycles
gather and process the
four categories of
opinion that drive our
actions and inaction
Foundation Document
F o u n d a t io n D o c u m e n t
F D T h e C u r r e n t S t a t e o f I n S ilic
T h e e n d o r s e d o p in io n s d e s c r ib in g th e c u r r e n t s t a t e , t r e
B e n e f it - C T , B e n e f it - P h a r m a ,
M a n y d e v ic e C T s tu d ie s in v o lv e a lo w n u m
T h e a p p lic a t io n o f I S C T is m in im a l w ith in
T h e r e a r e e x a m p le s o f s u c c e s s f u l I S C T .
T h e r e is e v id e n c e o f u s e . C o n f u s io n m a y
T h e r e is g r e a t in t e r e s t in I S C T in p h a r m a .
D e v ic e s , D is e a s e s , W h e r e , W h
A n e c d o t a l e v id e n c e s u p p o r t in g t h e s e s t a t
D e v ic e C T f a ilu r e s o c c u r m o s t in t h e la s t 1
I S C T w ill h e lp u s u n d e r s t a n d h o s t- d e v ic e
S o m e s im p le t a r g e t s w ill a p p e a r in b o t h t h
T h e r e a r e IS C T u s e d in P K P D , p e d ia t r ic s
T h e r e w ill b e g r e a t e r o p e n n e s s t o I S C T m
C a p a b ilitie s
I S C T w ill n e v e r r e p la c e e n t ir e ly c lin ic a l t r ia
D a t a , M o d e lin g , M o d e lin g - M e t
A p o o r e x a m p le o f u s in g I S C T is w h e r e g r
A n e x c e lle n t e x a m p le o f I S C T is w h a t is b
A t t e m p t s a r e b e in g m a d e t o r e p la c e s o m e
C o m b in a t o r ia l c h e m is t r y h a s e n h a n c e d d i
C o m p u te r b a s e d m o d e ls a r e b e in g u s e d t
F o r I S C T to u lt im a t e ly w o r k , w e w ill n e e d
G o o d e x a m p le s o f t h e p o t e n t ia l o f I S C T h
L a c k o f c la r it y r e g a r d in g d a t a m g m t a n d it
M ic r o f lu id ic s a n d n a n o te c h n o lo g y a r e h u g
M o d e lin g a n d s im u la t io n is b e in g u s e d b o
M o d e lin g a n im a l t o h u m a n - th e r e h a v e b e
P h a r m a c o lo g y m o d e ls d o e x is t fo r u n d e r s
P r o b le m s t h a t h a v e b e e n e n c o u n t e r e d in
Q u a n t it a t iv e s y s t e m s p h a r m a c o lo g y is a n
T h e r e a r e fe w e x a m p le s o f m o d e ls t h a t c a
W e c a n b e g in t o a d v a n c e I S C T w it h th e s
W e h a v e n o t y e t e x p lo it e d t h e m o d e ls a n d

14. The Alignment Cycle
translated ‘We each think’
into
-We are here
-We should go there
-This is how to get there
The Alignment Cycle
translated ‘We each think’
into
-We are here
-We should go there
-This is how to get there

15. Class Analysis
• Alignment within a
class (balls)
• Alignment between
classes (lines)
• Green= excellent,
Yellow= good
• Line thickness= level
of alignment
• Table- detail of
alignment levels
across categories
• Industry statistics show standard alignment
index is in the order of 44-83
•Avicenna is very high by comparison
•Indicates strong basis for future collaboration
• Industry statistics show standard alignment
index is in the order of 44-83
•Avicenna is very high by comparison
•Indicates strong basis for future collaboration

16. Summary of AO delivery
• What we have
– A refined and comprehensive view of the
stakeholder landscape
– A better understanding of what constitutes “ISCT”-
beyond Clinical Trials
– Key, detailed data on topics and areas of focus
• How we are applying it
– The foundation content to build the detailed
Roadmap
– Building a time-phased action plan for implementing
the Roadmap

17. Biomedical Industry
clinical trials
industry
clinical trials
industry
Virtual Prototype
industry
Virtual Prototype
industry
IT industry
CAE tools
CRO
Regulatory
Engineering
firms
Research
hospitals
“Engaged Discussants”
Community
of Practice
Roadmap Industrial Alliance
Informs

18. Alliance Objectives
• Prototype & build confidence in
application of CM&S
• To lobby the EC to fund ISCT in H2020
• Develop a mid/long term vision for
ISCT

19. Alliance Activities➨
• Develop and disseminate “Good Modelling Practices” for the
use, verification, validation, and accreditation of ISCT
• Promote events that foster interdisciplinarity and related
training
• Promote, sustain, and disseminate data and model sharing
• Develop educational content and provide targeted training
• Maintain an observatory of all ISCT success stories
• Secure funding for ISCT research and technological
development
• Drive necessary standardisation and interoperability efforts

20. Alliance is focused on PoP

21. Alliance: Lobbying & Influencing
• A European Trade Association for in
silico medicine
• Market focused
• A platform for industries and research
institutions to discuss bottlenecks to
progress on in silico medicine
• The go-to Association for all things in
silico in European Politics.

22. General Benefits for Members
• Targeted at all those with a vested interest in the in
silico market eg: Pharma, Medtech, Cosmetics,
Software industries, Research institutions
• Ability to set the policy and advocacy agenda of
the Association in year 2
• Access to Rohde Public Policy expertise/VPH
PAWG analysis of all Regulatory and policy issues
affecting specific market interests
• Potential opportunity to create new funding
streams for in silico research: Public Private
Partnership

23. Public Private Partnership
• EC conversation -> invitation to
consider more ambitious
alternative to Alliance concept
• Work with industry to scope a
plan and make a proposal
• Industry-driven, EC, Academics
• Implications- financial (huge),
governance, oversight, legal and
ethical, management
• Potential to move from
demonstrating evidence of utility
to full implementation and
ultimately routine practice

24. Written interest from …

25. PPP: PoP -> Adoption

26. Current Status
• Outreach to industry ongoing
• Likely that key MEP will be honorary President
of the Alliance
• First gathering of emerging Alliance partners in
Barcelona in June
• Exploratory discussions with EMA held
• Active discussions with EFPIA- link to IMI2 and
SGGs
• Contact with EC ongoing to ensure feasible
timeline for PPP submission

27. “The Virtual Physiological Human (VPH) will
revolutionise the way health knowledge is
produced, stored and managed as well as the
way in which healthcare is currently delivered”
- European Commission

28. AVICENNA
EVENT 5
Hosted by AQuAS
Agency for Health Quality and Assessment of Catalonia
4th and 5th June 2015, Barcelona, Spain
In Silico Clinical Trials: the future is now

29. Thank you
Adriano Henney