Contact: kevin.breesch@toxikon.be

Contract Laboratory Services

CRO SolutionsBioVille, 19th September 2012

CONTENT OF PRESENTATION

» History

» Company Profile

» Current Services

» Proof-of-Concept (R&D)

» Preclincal Tox: in vivo and in vitro toxicology (GLP)

» Analytical Services – material characterization / Stability

(GMP)

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Company Profile

TOXIKON – COMPANY PROFILE

C.R.O.

Headquarters: Bedford, MA

European Lab Facility: Leuven, Belgium

30 Years of experience in Preclinical Testing for the Medical Device,

Pharma and Biotech Industry

> 10 Years of analytical and microbiology expertise Medical Device

and the Pharma Industry

FDA Registered, ISO 17025 Accredited, GMP & GLP compliance

testing

>190 Researchers

1977 company founded as Cambridge Diagnostics

1982 became Toxikon Corporation

1991 opened European office, Belgium

2002 Focus on E&L and Medical Devices

2007 new facility European labs (2000 m²)

TOXIKON – COMPANY HISTORY

Medical Devices

Markets

» Pharmaceutical Packaging Industry

» Pharmaceutical Industry

» Biotech and Diagnostic Industry

Pharmaceutical & Biotech Services

Extractables & Leachables

Facts & Figures

» Privately owned company

» Total sales US (2011) : EUR 25 MIO

» Total sales Europe (2011) : EUR 8 MIO

» Toxikon US : 145 Employees

» Toxikon EU : 45 Employees

» 30% at PhD level

GROWTH LABORATORY ACTIVITIES - EU

TOXIKON Europe – COMPANY PROFILE

Analytical chemistry In support of:» Extractables & Leachables» Stability & Lot Release testing

State of the Art Technology:» GC/MS, HS-GC/MS, PTV-GC/MS, GC-TOF, GC-FID» LC-UV (DAD), LC/MS (Ion Trap), LC/MSMS, Orbitrap» ICP-OES, AAS, IC, TOC, IR

Microbiology testing Services (Europe)» Sterility Testing (EP 2.6.1 / USP <71>)» Sterilization & Cleaning Validation Studies» Bioburden (MLT EP 2.6.12) testing, EM & microbial

identification (MID)» Bacterial Endotoxin testing (EP 2.6.14)

Quality Credentials

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System/Authority Europe USA

ISO 17025:2005 √ BELAC √ ACLASS

GMP √ FAGG √ FDA

GLP √ WIV √ FDA

FDA registration √ √

AAALAC/MSPCA/OLAW √

NRC (radiolabeling studies)

√

US-laboratories

EU-laboratories

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Proof-of Concept

Proof-of-concept

» PK/PD studies» Oncology (Xenograft Tumor Models)

• Prostate cancer: LNcap, DU145, PC-3• Lung Cancer:NCI-H460, NCI-H69, HOP-92• Breast cancer: MDA-MB-468, MCF-7, MCF-7 (MDR+), MDA-MB-

231• Liver Cancer: PLC-5, Hep3B• Colon: HT29, COLO-205• Pancreatic Cancer:PANC-1• Brain: US7MG• Promyelocytic: HL-60, THP-1• B cell lymphoma: Ramos, RaJI

These are the models we have validated and using for our clients. However we can develop any other type of tumor models.

Proof-of-concept

» Inflammatory Diseases • Rheumatoid Arthritis (RA)• Inflammatory Bowel Diseases (IBD)• Multiple Sclerosis • Atopic Dermatitis• Allergic Contact Dermatitis (ACD)• Lung Disease• Diabetes and Obesity Models

» Ocular Programs• Dry eye• EAU Uveitis• Glaucoma / IOP• Corneal NV / AMD• Choroidal NV / AMD (Subretinal NV)• Retinal NV / AMD, DR

These are the models we have validated and using for our clients. However we can develop any other type of tumor models.

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Preclincal Toxicology (GLP)

Preclincal Toxicology (GLP)

Biological License Application (BLA)

Enabling Studies

» A BLA for a biologic drug (i.e. native molecule, protein, antibody, cytokine, etc.) follows ICH Guidance S6 which specifies a case-by-case program design:• Single dose and repeat dose toxicity• Genetic toxicology: AMES, Chromab and MNT• Reproductive end developmental toxicity• Carcinogenicity • Tissue-Cross-Reactivity (mAb)

» Study desings in order to mimic the clinical dosing regimen, using preferably GMP material, as intended for Marketing Authorizations

» Proteins i.e. break down to native amino acids and so are “safe” and produce safe metabolites.

» Generally, no genotoxicity tests are required.

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IND Programs

Biological License Application (BLA)

Enabling Studies (cont.)

» Toxicity mechanisms are: off-target effects and exaggerated pharmacology requiring tox studies in at least one relevant or surrogate species. Primates are often the tox species.

» Safety Pharmacology on major physiological systems CNS, CVS and respiratory can be integrated in toxicity studies

» Biologics, require immunotoxicity/ neutralizing antibody evaluations with assay development and validation to examine blood samples.

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IND Programs

Biological License Application (BLA)

Enabling Studies (cont.)

» Toxicity mechanisms are: off-target effects and exaggerated pharmacology requiring tox studies in at least one relevant or surrogate species. Primates are often the tox species.

» Safety Pharmacology (CNS, CVS, pulmonary) can be integrated in toxicity studies

» Biologics, require immunotoxicity/ neutralizing antibody evaluations with assay development and validation to examine blood samples.

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Analytical Services – material characterization / Stability (GMP)

Analytical Services (GMP/GLP)

» Compound purity and stability (ICH Q5C) • SEC HPLC• SDS-PAGE• IEF• Cell Potency assay• ELISA

» Other parameters• Particulate matter• Osmolarity• Sterility• Endotoxins• Mycoplasma• Residual DNA• Viral clearance

THANK YOU!