Faster from First Time in Human to Proof of Concept

Charité Research OrganisationJuly 2016

Founded in 1710

Largest university hospital in Germany

17 centres with over 100 clinics

CHARITÉ – UNIVERSITÄTSMEDIZIN BERLIN

CHARITÉ RESEARCH ORGANISATION CHARITÉ OWNED - OPERATIONALLY INDEPENDENT – FOR PROFIT

Phase I/II unit with 30+ beds, 500sqm out-patient facility and a dedicated team

Facilitate a single centre solution for early clinical studies in HVs and patients whenever possible

Deliver Proof of Concept faster via more effective use of university hospital resources

267 FTIH- POC PROJECTS TO DATEFROM MORE THAN 50 INDUSTRY SPONSORS

Projects By Primary Area, March 2016

Cardiolo

gy

Clinica

l Pha

rmac

ology

Consu

ltanc

y

Dermato

logy

Endoc

rinolo

gy

Gastro

enter

ology

Immun

ology

Infec

tiolog

y

Nephro

logy

Neurol

ogy

Nutritio

n

Oncolo

gy

Psych

iatry

Pulmon

ology

Rheum

atolog

y

Urolog

yOthe

r0

2

4

6

8

10

12

14

16

18

20

22

24

26

28

30

Completed In Progress In Preparation

OPERATIONAL CHALLENGES IN EARLY CLINICAL TRIALS

Recruitment

Expertise

Resources

CRO RESOURCES

Around 100 FTEs and 50 support staff

CRO SERVICES

Internalised Partnered

Scientific & Regulatory Consultancy

Project Management

Protocol Development

Ethical & Regulatory Submissions

Clinical Conduct

Medical Writing

Routine Laboratory Analysis

Biomarker Validation & Analysis

GMP Pharmacy

Monitoring

Data Management

Statistical Analysis

CRO’s CENTRES OF EXCELLENCE APPROACH

Independent Phase I/II unit

and team

Methodological and scientific support from therapeutic

area experts

Access to key technologies such

as MRI

Access to specialist biomarker research and laboratory capabilities

Patient recruitment via dedicated team using database and advertising

Clinicians share expertise Clinics provide access

Scientists utilise

research

IMAGING CENTRE OF EXCELLENCE

MRI with central scoring services, PD Dr. med. Kay-Geert Hermann

Ultrasound expertise via Prof. Dr. med. Marina Backhaus, developed US 7 score

Leading the way in use of Florescence Optical Imaging in rheumatology

BIOMARKER CENTRE OF EXCELLENCE

Prof. Hans-Dieter VolkScientific Director

PD Dr. Gerlald GrützHead of Laboratory

Immunological Study Laboratory (ISL)

10 colour flow cytometer

Hematology analyzer

Multiplex ECL

Multi-analyte ELISA

Multiplex Luminex

ELISA-Reader

Off the shelf assays

Transfer and validation of sponsor assays

Research laboratory

DIN EN ISO 15189

DIN EN ISO/IEC 17025

EXCELLENCE IN ALL PARTNERSHIPS

Accredited laboratory providing routine and advanced analysis capabilities, serving the

pharma and CRO industries for more than 15 years

Pharmacy with GMP license and dedicated clinical trials support, serving the pharma

and CRO industries for more than 20 years, providing on-site pharmacist support and

manufacturing capabilities

Patients Enrolled Per Site 0 - 5

% of Sites Contributing Zero

Patients20-30%

CHALLENGING THE CONVENTIONAL PATIENT STUDY APPROACH

It’s expensive to set-up and quite ineffective

Would be much better if you could bring (most of) the patients to a single central unit…

DOES A PHASE III-STYLE APPROACH WORK IN EARLY DEVELOPMENT?

Tends to limit what you can do in a study – lowest common denominator, logistics issues

CRO RECRUITMENT APPROACH

Appeal directly to the patient

Financially compensate the patient properly+

Have the resources to treat the patient with utmost respect

+

SINGLE CENTRE PHASE IIa SJÖGREN’S STUDY – GERMAN WIDE RECRUITMENT

Work with KOL’s for indication expertise

German wide recruitment using FB and Google

Allowed 1 site solution instead of 17 site solution

All patients received financial compensation

n=27 patients enrolled, 11 from Berlin, 16 from German wide recruitment

FTIH-POC STUDY EXAMPLES

Indication Key Criteria Phase Type Design Enrolled n= Screened n=Avg. Enrolment Rate / Month

Key Methods

RA DAS28 ≥ 3.2 FTIH Single-CentreSAD i.v., SAD s.c., MAD s.c.

92 134 8

DAS28, MRI, ultrasound, PD markers, local RO assessments

SLE

SELENA-SLEDAI 2-9, autoantibody positive

Phase I Multi-CentreMAD s.c., SD s.c.

21 56 3

SLELENA-SLEDAI, BILAG, Lupus-QoL, PD markers

Sjögren's

ESSDAI ≥ 6, elevated serum titers, antibody positive

Phase IIa Single-Centre SAD i.v. 27 55 3

ESSDAI, PD markers, salivary flow, salivary gland biopsy

RA & Psoriasis

RA: diagnosis > 3 months, on MTXPsoriasis: Diagnosis > 6 months, stable, no MTX

Phase I Single-CentreMAD i.v., MAD s.c.

RA: 24Psoriasis: 60

RA: 48Psoriasis: 156

RA: 8Psoriasis: 8

PASI, target lesion score, PD markers

HV & Crohn's

HV: restricted lab rangesCrohn's: remission with CDAI ≤ 150

FTIH Single-CentreSAD i.v., SAD s.c.

HV: 64Crohn's: 24

HV: 184Crohn's: 37

HV: 8Crohn's: 6

CDAI, PD markers

FTIH-POC STUDY EXAMPLES

Indication Key Criteria Phase Type Design Enrolled n= Screened n=Avg. Enrolment Rate / Month

Key Methods

HV & Asthma

HV: restricted lab & ECG rangesAsthma: FEV1 ≥ 70% pedicted with ≥ 12% reversibility

FTIH Single-Centre MAD oralHV: 80Asthma: 54

HV: 235Asthma: 98 (pre-screening study 244)

HV: 80Asthma: 27

Spirometry, PD markers

MS (Progressive)

Diagnosis of primary forms of MS

FTIH Single-CentreSAD i.v., SAD s.c.

44 87 4EDSS, MRI, PD markers

HIVHIV-1 Clade B, C

Phase IIa Multi-Centre MAD. Oral 91 150 8Long in-house stays (30 days), viral load, CD4+

HCV HCV GT1, GT3 Phase I Single-Centre MAD Oral 54 102 3 Viral load

HV & T2D

HV: restricted lab & ECG rangesT2D: overweight, metformin

Phase I Single-Centre MAD s.c.HV: 40T2D: 36

HV: 129T2D: 116

HV: 16T2D: 6

Long in-house stays (21 days), PD markers, holters

INNOVATION – PRE-SCREENING STUDIES

n=244 asthma patients identified and pre-screened against key study inc/exc. criteria before

and during conduct of HV part

n=108 considered to be “probably” eligible for main study

n=98 entered into main study screening

n=54 enrolled in just over 2 months in 2 parallel

cohorts of 27

Pre-screening study approved by local ethics

Core block of patients identified to push to main

study

Ultimately n=98 retained for main study screening

n=54 enrolled

INNOVATION – WORLD FIRSTS

World’s first clinical trial (CV area) conducted under micro-gravity conditions somewhere over the Atlantic Ocean

THANK YOU

Charité Research Organisation GmbHCharitéplatz 1, 10117 Berlin, Germany

www.charite-research.org