Tr a n s l a t i n g p r e - c l i n i c a l f i n d i n g s

i n t o s u c c e s s f u l c l i n i c a l t r i a l s

Wahid Awad, Ph.D, Chief Business Officer

ARO 2021

CILcare is the leading external innovation R&D partner in

hearing disorders

2

Paris,

France

Montpellier, France

Headquarter

PK/PD

Boston, MA, USA

GLP facilities

Copenhagen,

Denmark

Pharmaceutical

Nutraceutical

Veterinary

Medical devices

+120Studies

+60Sponsors

2Labs

Established in France, US & Denmark, CILcare operates worldwide since its inception in 2014

A CATALYST of the hearing disorders area!

3

• Strongly involved in patient

associations

• Collaborating with a global

network of preclinical & clinical

CRO partners & consultants

• Frequently publishing in

international peer review journals

SPONSORS

• Working with internationally

recognized KOL from industry &

academia

• Continuously building strategic

industrial partnerships

• Speaking in international

scientific conferences

ARO

Patients

Think clinical development

Portfolio Screening

Design TPP

+

R&D Plans

Pre-formulation

+

PK

Preclinical

Efficacy

Ototoxicitytesting

&

GLP Tox

IND Phase I Phase II

I n d i c a t i o n ● r o u t e o f a d m i n i s t r a t i o n ● e n d p o i n t s

4

In preclinical studies, select the best:

MODEL DRUG REGIMEN READ-OUTS

Clinical protocol

Models for auditory research & development

5

COCHLEAR

EXPLANTS

ZEBRAFISHOTIC

CELL LINE

SCREENING PHASE

PK TOLERANCE GLP-OTOTOXICITYEFFICACY

RODENTS & LARGE SPECIES

Mice Rats Guinea pigs Chinchillas Mini pigs Sheep

Select your model to target your clinical indication

6

• Age-

related

hearing

loss

• Salicylate-

induced

tinnitus

• Noise-

induced

tinnitus

• Noise-

induced

hearing

loss

• Otitis

media

• Drug-

induced

hearing

loss

• Gene

therapy

PRESBYCUSIS TINNITUS HEARING LOSS OTOTOXICITY GENETIC DEAFNESS OTITIS MEDIA

MICESAMP8

RATSLong Evans

RATSWistar

GUINEA PIGSHartley

RATSWistar

MICECBA

RODENTS

MINI PIGS

SHEEP

CHINCHILLAS

Bastard F1N1

Design efficacy study mimicking clinical situation

Formulation

Administration regimen

Read-outs

7

Differentiate POC studies from efficacy studies in terms of:

Preventive versus

curative / regenerative treatment

For slow / Sustained release

Translational read-outs

Select translational and complementary measures

MEMRI

BEHAVIORAL MEASURES

GPIAS(Gap-Prepulse Inhibition of the

Acoustic Startle reflex)

OTOSCOPY

COCHLEOGRAM

HISTOLOGY

Non invasive & recognized read-outs Complementary measurements

DPOAE(Distorsion Product

OtoAcoustic Emissions)

RIBBON

SYNAPSES COUNT

GROSS

ASSESSMENT

OF THE MIDDLE

EAR

CLINICAL SIGNS

GENE & PROTEIN

ARRAYSBiochemical biomarkers

ABR(Auditory Brainstem

Responses)

WAVE I

ANALYSIS

TYMPANOMETRY

SEM(Scanning Electron

Microscopy)

8

Expert

team

Reproducible

data over

time

Working on robust and reproducible models

9

Experiments

conducted in a

high-quality

acoustic

environment

High

throughput

measures

Cisplatin 13mg/kg L+R

Frequency (Hz)

0 5000 10000 15000 20000 25000 30000 35000

AB

R t

hre

sh

old

s (

dB

SP

L)

Me

an

± S

EM

10

20

30

40

50

60

70

80 Baseline (n=50)

T+3days (n=50)

l l ll l l

www.cilcare.com l info@cilcare.com

Thank you for your attention !Feel free to contact me:

wahid.awad@cilcare.com