Corporate presentation 2015

www.neuroservice.com
CORPORATE
PRESENTATION
November, 2015

SUMMARY
OUR
SOLUTIONS
OUR
COMMITMENTS
YOUR
INTERLOCUTORS
WHO
WE ARE
OUR
TECHNIQUES
OUR FOCUS
AREAS

WHO WE ARE
OUR
SOLUTIONS
OUR
COMMITMENTS
YOUR
INTERLOCUTORS
WHO
WE ARE
OUR
TECHNIQUES
OUR FOCUS
AREAS

WHO WE ARE
Core business activity
A Contract Research Organization (CRO)
Testing the effect of ANY COMPOUNDS
on Central Nervous System tissues

WHAT WE DO
Core business activity
IN VITRO TESTS
UNDER PHYSIOLOGICAL CONDITIONS
In rodent (or human) acute brain slices
In rodent spinal cord slices
In rodent cultured neurons

www.neuroservice.comwww.neuroservice.com
WHAT WE DO
In vitro Electrophysiological recordings

WHAT WE PROPOSE FOR DRUG DISCOVERY
Your remote laboratory
Hits
Leads
Advanced
candidate
IND
LEAD
SELECTION &
OPTIMIZATION
MECHANISM
OF ACTION
SAFETY &
TOXICOLOGY
PROFILING
CLINICAL RESEARCH
R&DPRÉ-CLINICAL
DEVELOPMENT

WHO WE ARE
Key features
Launched in 2006
150 studies
Clients: Pfizer, Roche, CHDI…
25 people – 2 laboratories
Capital: 520 000€
Income 2014 : 2,7 M€
80

OUR TECHNIQUES
OUR
SOLUTIONS
OUR
COMMITMENTS
YOUR
INTERLOCUTORS
WHO
WE ARE
OUR
TECHNIQUES
OUR FOCUS
AREAS

OUR TECHNIQUES
Multi-Electrode Arrays (MEA) technique

OUR TECHNIQUES
Patch-Clamp technique

OUR TECHNIQUES: THE IDEAL COMBINATION
Patch-Clamp
Electrode
MEA Electrode

OUR TECHNIQUES: A COMPREHENSIVE COMBINATION
Different structures and protocols
MATERIAL STRUCTURE PROTOCOL
Input/Output Properties
Paired-Pulse Protocol
Basal Synaptic Transmission
Long-Term Potentiation
Long-Term Depression
Short-Term Potentiation
Firing Activity
Dose-Response Protocol
Spontaneous Postsynaptic Current
Agonist Evoked Postsynaptic Current
Pharmacology of Intracellular Pathways
Hippocampus
Cortex
Cerebellum
Spinal Cord with or without root
Ventral Tegmental Area
Striatum
Substantia Nigra
Locus Coeruleus
Periaqueductal Gray Matter
Dorsal Raphe
Amygdala
Thalamus
Dorsal Vagal Nucleus
i
In vitro
rodent slices

OUR TECHNIQUES: THE IDEAL COMBINATION
In vitro evaluation of compounds under the most physiologically relevant conditions
Robust and reproducible high quality data
Reducing animal and compound use
Exceptional macroscopic view of neuronal
networks
Ability to record multiple evoked-responses in
parallel within a single slice
Mid-throughput production capabilities
Refined investigation of compounds’ effect on
single proteins/receptors
Large catalog of CNS structures and neuronal
cell types to address effects on specific neurons,
neurotransmitter systems or receptors
NEURONAL NETWORK SINGLE NEURON
PATCH-CLAMPMEA (Multi-Electrode Arrays))

HAND-MADE MID-THROUGHPUT SLICE ELECTROPHYSIOLOGY
10 MEA SET-UP
UP TO 200 VALIDATED SLICES / WEEK
PATCH-CLAMP RECORDINGSMEA RECORDINGS
8 PATCH-CLAMP SET-UP
UP TO 50 VALIDATED NEURONS / WEEK
LARGE BANDWIDTH

OUR FOCUS AREAS
OUR
SOLUTIONS
OUR
COMMITMENTS
YOUR
INTERLOCUTORS
WHO
WE ARE
OUR
TECHNIQUES
OUR FOCUS
AREAS
Drug Discovery
Safety

OUR THERAPEUTIC AREAS
SOLUTIONS
FOR CNS
DRUG
DISCOVERY
SOLUTIONS
FOR
SAFETY
Testing the effect of any
type of drug, molecule…
on CNS and investigate its
mechanism of action
NEURODEGENERATIVE
DESEASES
PAIN
COGNITION
EPILEPSY
PSYCHIATRY
ALZHEIMER
HUNTINGTON
PARKINSON

SOLUTIONS FOR
CNS DRUG DISCOVERY

MEA RECORDINGS
Spontaneous firing in Cerebellum

MEA RECORDINGS
Spontaneous Firing in Substantia Nigra
0 . 0
0 . 2
0 . 4
0 . 6
0 . 8
1 . 0
Normalizedspontaneousfiring
C o n t r o l 2 0 µ M
i s r a d i p i n e
p = 0 . 0 1 2
p < 0 . 0 0 1
3 0 µ M
d o p a m i n e
0 1 0 2 0 3 0 4 0 5 0 6 0
0 . 0
0 . 5
1 . 0
1 . 5
T i m e ( m i n )
Normalizedspontaneousfiring
3 0 µ M d o p a m i n e ( 1 5 m i n ) + 2 0 µ M i s r a d i p i n e ( 2 0 m i n )
( 5 r a t s , 6 s l i c e s , 1 1 e l e t r o d e s )
c
o
n
tro
l
3
0
µ
M
d
o
p
a
m
in
e
w
a
sh
o
u
t
2
0
µ
M
isra
d
ip
in
e

MEA RECORDINGS
LTD - LTP in hippocampal slices
Between 1 and 20 Hz, the stimulations train
induces Long-Term Depression (LTD) of evoked-
responses.
At 100 Hz and 200 Hz, the stimulations train
induces Long-Term Potentiation (LTP) of evoked-
responses.
Stimulation trains with a wide range of frequencies (from 1 to 200 Hz) provide a means to
determine the LTD/LTP “crossover point”.
1
H
z
10
H
z
20
H
z
50
H
z
100
H
z
200
H
z
-1 0 0
-5 0
0
5 0
%offEPSPchange
(atendpoint)
LT D
LTP
C ro sso v e r
p oin t
The LTD/LTP crossover point is close to 50
Hz. Indeed, a 50 Hz stimulation train does
not substantially modify the fEPSP
amplitude.
21

MEA RECORDINGS
4-AP-induced EDs in hippocampal slices
5 3 5 6 5 9 5 1 2 5 1 5 5
0 .0
0 .1
0 .2
0 .3
0 .4
0 .5
T im e (m in )
EDrate(Hz)
Averaged/1min
5 0 µ M 4 -A P
[1 ] [2 ]
cp d x
3 0 0 µ M P h e n o b a rb ita l
[3 ]
0 20 40 60 80 100
0.0
0.2
0.4
0.6
Time (min)
EDrate(Hz)
Averaged/30s
50 µM 4-AP
Phenobarbital
100 µM 500 µM300 µM
Phenobarbital induced a stable reduction
of the ED frequency over a 2.5 hours
recording period (orange trace).
Application of a new AED (cpd x, for 3
concentrations), with Phenobarbital, is
examined over the same period (blue
trace).
50 µM 4-AP rapidly triggers EDs which
stabilizes around 0.4 Hz. Then, application
of increasing concentration of
Phenobarbital shows a dose-response
decrease of the ED frequency.
DRUG-DRUG INTERACTIONS

MEA RECORDINGS
Kainate-induced oscillations in hippocampal slices

MEA RECORDINGS
Tg2576 model profiling
 The strength of synaptic transmission is significantly lower in WT than in Tg2576 mice.
 The paired-pulse facilitation is significantly impaired in Tg2576, especially for the shortest inter-
stimulus intervals.
 The LTP amplitude is significantly altered in Tg2576, compared to that in WT mice.
I/O cu rv e
0 2 0 0 4 0 0 6 0 0 8 0 0
0
5 0 0
1 0 0 0
1 5 0 0
2 0 0 0
T g 2 5 7 6
W T
S tim u lu s In te n sity (µA )
fEPSP(µV)
P a ire d P u lse R a tio
0 1 0 0 2 0 0 3 0 0
0 .6
1 .0
1 .4
1 .8
T g 2 5 7 6
W T
In te r-stim u lu s In te rv a l (m s)
fEPSP2/fEPSP1
Lo n g -T e rm P o te n tia tio n
0 1 0 2 0 3 0 4 0 5 0 6 0 7 0
1 .0
1 .4
1 .8
2 .2
T g 2 5 7 6
W T
T im e (m in )
NormalizedfEPSPamplitude
24

SOLUTIONS FOR DRUG DISCOVERY
mIPSC in hippocampal pyramidal neurons
CHOLINERGIC RECEPTOR-MEDIATED INCREASE
OF CA1 PYRAMIDAL NEURONS FIRING
CARBACHOL &
PIRENZEPINE
EXPERIMENT
Miniature inhibitory postsynaptic currents (mIPSCs) in
hippocampal neurons
DATA
mIPSC frequency, amplitude distribution and detailed
analysis of the average mIPSC waveform
(including amplitude, rise time, decay time)

PATCH-CLAMP RECORDINGS
Characterization of sodium currents in DRG from neuropathic animals
Mice DRG (12 weeks) Rat DRG (12 weeks)
Control n=10
Neuropathic n=11
Control
Control
Or
Neuropathic

PATCH-CLAMP RECORDINGS
Recording of the evoked Glycine currents in lamina II neurons from spinal cord
100 pA
5 s
100 pA
5 s
20 µM Glycine
20 µM Glycine
100 pA
5 s
20 µM Glycine
Control
Control + PAM X
Control + PAM X
+ Strychnine
Normalizedamplitude
100 %
200 %
300 %
0 %
20 µM Glycine
20 µM Glycine
20 µM Glycine

HUMAN BRAIN SLICE RECORDINGS
NMDA currents recordings in human cortex slices
Evoked-currents are completely blocked by a selective NMDA antagonist.
NB: All experiments could also be provided on AMPA/Kainate and GABA-A receptors.
40 ms
50 pA
CONTROL
R-CPP 10 µM
4 8 12 16
0
-50
-100
-150
-200
-250
EPSC-Amplitude(pA)
Time (min)
R-CPP
Vhold = -30 mV

SOLUTIONS FOR SAFETY

SOLUTIONS FOR SAFETY
Focus areas
CUSTOMER WORK FLOW
Advanced candidate
MECHANISM
OF ACTION
SAFETY &
TOXICOLOGY
PROFILING
CLINICAL RESEARCH
Safety Studies
!

NEUROSAFETY PACKAGE
General profiling on synaptic properties
●
At least one effect detected
!
PROPOSAL FOR FURTHER INVESTIGATION

PRO-CONVULSIVE PACKAGE
Prediction of convulsive properties
●
At least one effect detected
TEST 1, TEST 2 or TEST 3
TEST 1 TEST 2 TEST 3 OK● ●●
!
PROPOSAL FOR FURTHER INVESTIGATION

OUR SOLUTIONS
OUR
SOLUTIONS
OUR
COMMITMENTS
YOUR
INTERLOCUTORS
WHO
WE ARE
OUR
TECHNIQUES
OUR FOCUS
AREAS

OUR SOLUTIONS
Neuroservice: your remote laboratory
Outsourced R&D Assays Customized Solutions Packages
DRIVE
OUR RESSOURCES
CUSTOMIZE
OUR ASSAYS
CHOOSE
A READY TO USE
SOLUTION
Highly experienced team in
neurophysiology,
neuropharmacology
and neurotoxicology
Portfolio of 150 studies
• High quality data
•Short turnaround time
•Mid-throughput production
capabilities
4 packages:

OUTSOURCED R&D
Highly skilled scientists
Flexible Multi-Platform
FTE Contract

R&D CONTRACT
The study: how does it work?
START
STOP
RUN 1 RUN 2
MONTH 1 MONTH 2 MONTH 3…
RUN 3 RUN 4
INVOICE1
INVOICE2
INVOICE3
GO GO GO

CUSTOMIZED SOLUTIONS
More than 400 studies performed !
Fee for Service
Contract

OUR COMMITMENTS
OUR
SOLUTIONS
OUR
COMMITMENTS
YOUR
INTERLOCUTORS
WHO
WE ARE
OUR
TECHNIQUES
OUR FOCUS
AREAS

OUR COMMITMENTS
QUALITY ROBUST AND REPRODUCIBLE DATA
SHORT TURNAROUND 200 VALIDATED SLICES OR 50 NEURONS / WEEK
EXPERTISE INTERACTIVE AND EXPERT SUPPORT
FLEXIBILITY STEP-BY-STEP STUDY PLANS
ETHICS MINIMIZED ANIMAL USE

YOUR INTERLOCUTORS
OUR
SOLUTIONS
OUR
COMMITMENTS
YOUR
INTERLOCUTORS
WHO
WE ARE
OUR
TECHNIQUES
OUR FOCUS
AREAS

YOUR INTERLOCUTORS
BRUNO BUISSON, PhD
Founder
General manager &
Chief scientist
SCIENTIFIC TEAM
Based in JapanBased in USA
TATSUO MIYAUCHI, PhD
Scientific liaison
JEFFREY SPROUSE, PhD
Scientific liaison
OLIVIER TOURY
Co-Founder
Deputy general manager &
Chief of business
development
MAI SAITO
Asia Business Developer
LINDA HOUAICHI
USA & Europe Business
Developer
ESTHER STEIDL, MsSc
Co-founder
Head of the Multi-Electrode
Array laboratory
BOGDAN SAVA, PhD
Head of the Patch-Clamp
laboratory
BUSINESS TEAM

www.neuroservice.comYour partner for hands-on CNS electrophysiology
Domaine de St Hilaire
595, rue Pierre CS 30531
13 593 Aix-en-Provence
Cedex 3
FRANCE
Tel : +33 (0)442 991 220
contact@neuroservice.com

Corporate presentation 2015

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