IMI2, Hôpital Saint-Antoine, Paris/ 09-Sept-2014

IMI Projects : SMEs Contributions and Benefits from Large Public-Private Initiatives on Precompetitive Projects

Prof. Hüseyin FIRAT, MD,PhD

IMI SAFE-T Applicant Consortium coordinatorPartner of the IMI BT-Cure and Pharmacog consortia

OverviewBiomarker Discovery, Development and Regulatory Qualification

Firalis

Amoneta

Diagnostic

TcLandExpression

Biomarkers on Cardiovascular DiseasesFounded in 2007

Biomarkers on Inflamatory DiseasesAcquired by Firalis in July 2013

Biomarkers on AlzheimerCreated on January 2014

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IMI SAFE-T Consortium

IMI Pharmacog Consortium

IMI BT-Cure Consortium

Company Overview

Thanks to IMI projects, Firalis gained overall expertise and cumulated know-how, andbecome an acknowledged key player in the field of biomarker qualification.

Firalis develops, manufactures and markets biomarkers (BM) and BM-based tools for drugdevelopment and clinical applications.

Firalis business model stands on a tripod :

I. BIOMARKER R&D : Firalis research activities focus on biomarker qualification in specificcardiovascular disorders. In this parallel, Firalis joined several international programs includingthe IMI-JU SAFE-T Project, where it has coordinated the consortium during initial phase.

II. BIOMARKER PRODUCTS : Firalis develops, manufactures and markets BM-based diagnosticsolutions; which are first marketed as «Research-Use-Only» (RUO) kits and then transforminto «In Vitro Diagnostics» (IVD) tools, upon clinical validation and regulatory qualification ofbiomarkers used in the corresponding kit.

III. BIOMARKER SERVICES : Firalis is conducting several research projects with and for the bio-pharmaceutical industry.

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Cardiovascular IVD Products

• CardioScan100• VascularScan100• Extension of RUO range• IVD clinical studies

• Extension of RUO and IVD range• Regulatory filing for IVD products• Marketing • Co-development of BM candidates

SAFE-T Project Impact at Firalis

developing biomarkers for cardiovascular disorders

Co-CHIPS ProjectOSEO funded Firalis SAS University of FREIBURG / IMTEK

Laboratory facilities :

Assay development, & Testing

• First Products RUO• Pre-IDE for IVD candidates

ISO17025 accreditated and ISO13485 certified labsISO9001 certified R&D NF96 900 compliant Biobanking

(1) RUO : Research Use Only(2) IVD : In Vitro Diagnostic

Validation of RUO products

Qualification of RUO products In clinical samples

Co-SAVE Project: biomarkers for drug-induced cardiovascular risks

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Firalis clinical BM qualification platform

The qualification of biomarkers requires close cross-talks in numerous fields of expertise. Firalis created a network of clinical centers of excellences, biobanks, biomarker laboratory, statistic and data mining groups to accelerate the translation of candidate biomarkers toward qualification in key contexts of use.

• ISO 17025: for testing

and calibration

laboratories

• ISO 9001: Quality

Management Systems

• ISO13485: Assay

development activities

• NFS96-900F: Quality of

biological resource

centres (BRCs)

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Key servicing activities

Biomarker

identification

Biomarker Assay

development

Biomarker data

analysis

Biomarker clinical

qualification

• Sample screening

• Literature search

• System biology

• Ab production

• Development of assays

• Validation of assays

• Testing activities

• Integrative data analysis

from pre & clinical studies

• x-omic data analysis

• Pathway analysis

•Predictive modelling

• Clinical Study design

• Biobanking

• Database creation and

maintenance

• Regulatory consultancy

Biomarker solutionsBiobanking and analytics

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Analytical testing Platform

Bead based MultiplexedimmunoassaysBioRad Luminex 200

Multimode readerELISA: Colorimetric, Fluorometric, Chemoluminescent

Ultra-sensitive immunoassaysSingulex Erenna® technology

qPCRABI PRISM 7900High throuput PCRand TLDA assays

Clinical chemistrySIEMENS Dimension EXL 200BiochemistryImmunology/serologyEnzymology

Planar Phase MultiplexedImmunoassaysMeso Scale DiscoverySector Imager 6000

Edge System by HTG MolecularFully Automated, Extraction Free Gene Expression Analysis

Multianalyte immunoessayCyplex platform

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IMI SAFE-T ConsortiumThe first launched IMI-JU project

First funded IMI-JU Project Initiated by Firalis as applicant coordinator

Start: June 2009, Duration: 6 years, Global budget: ~36 Mio €

Public consortium coordinator

Within SAFE-T, Firalis particularly focuses on drug induced cardiovascular toxicities

PSTC

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IMI SAFE-T ConsortiumThe first launched IMI-JU project

Three organs needing better clinical monitoring of drug-induced injuries

Kidney: current standards such as Urea and creatine increase only once 50-60% of kidney function is lost

Liver: current standards are not sufficiently sensitive and specific and do not adequately discriminate normal physiologic adaptation from pathologic phenomenon

Vascular System: currently no biomarkers available for drug-induced vascular injury in human

Objectives

Evaluate candidate safety BMs for monitoring drug-induced organ toxicities

Develop assays and devices for clinical application of safety BMs

Compile enough evidence to qualify safety BMs for regulatory decision making in drug development

Gain evidence for how safety BMs may also be used in the diagnosis of diseases and in clinical practice

• Duration: 5 years• Global budget: ~36 Mio €• Kickoff meeting: June 15, 2009

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SAFE-T Structure and Deliverables

• Evidence-based decision

making

• More reliable causality

assessment

• Better mechanistic

understanding

• Safer translation to

clinical development

• Earlier and more specific

signal detection

• Enhanced clinical

monitoring

Improved patient safety

Reduced attrition rates

Accelerated and safer

approval of innovative

medicines

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Key Achievements at Year 5Most challenges addressed, few concerns remaining

Excellent collaboration within the consortium

Biomarker qualification strategy defined

Biomarker candidates prioritized, assay development completed

Central biobank for sample storage up and running

Database and data capture system up andrunning

Collaboration with US based consortia : PSTC/C-Path initiated, VCRC and DILIN

New partners included in 2010/2011 toincrease capacity for clinical studies

Aquisition of 2/3 SMEs by bigmultinationals, a sign of attractivity andexcellence ?

Regulatory interactions via briefing meetings with EMA/FDA

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SAFE-T participants >200, www.safe-t.eu

Key Message from SAFE-T Experience

Large public–private cooperation, such as SAFE-T, provide great opportunities to develop precompetitive tools for drug development

All participants need to put their heart and soul,

Appropriate time provided to plan and execute such complex project

The IMI consortia are in an ideal position to provide their lessons learned

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IMI Program Attractivity for SMEsPros & Cons

Pros

• International working experience with EFPIA-Academia-other SMEs

• World-wide visibility, scientific and clinical excellence

• Possibility to collaborate with other consortia (e.g., PSTC/C-Path) and Health Authorities

• Acquisition of know-how, increased scientific and operational competence

• Ability to work in a quality environment with regulatory advise

• Availability and access to a variety of in-kind contributions from EFPIA members

• Possibility to exploit the IPs and market products for the Pharma industry

• Eased access to the Pharma market as potential clients

Cons

• Various perceptions of IP rights across the different stakeholders

• SMEs invest and lose money without direct benefit (Low indirect cost rate)

• EFPIA in-kind contribution is as yet significantly below target

• Collaboration with non-EU projects may lead to a diversion on EU research funding

• Redundant or un-necessary in-kind contribution from EFPIA, no reporting system established yet

• Acquisition of SMEs by big structures, introducing an imbalance among the SME partners

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Key Partners & References

Web-Imagint-FP7

Partners

Web-Mitocare-FP7 http://www.imi-safe-t.eu/

Clients

Othercollaborators

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• Located in a very active region of the Biovalley(Switzerland, Germany, France)

• 620 m² of lab space and biobanking, L2/L3 facilities

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