Toxikon is a contract research organization providing analytical, preclinical, and toxicology services. It has over 30 years of experience working with medical device, pharmaceutical, and biotech clients. The company has laboratories in the US and Belgium that are ISO 17025 accredited and GMP/GLP compliant. It offers a range of proof-of-concept, preclinical toxicology, and analytical chemistry services to support drug and device development from research through regulatory approval.

1. Contract Laboratory Services
CRO Solutions
BioVille, 19th September 2012
Contact: kevin.breesch@toxikon.be

2. 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)
2 CONFIDENTIAL

3. Company Profile
CONFIDENTIAL

4. 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

5. TOXIKON – COMPANY HISTORY
 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)

6. Pharmaceutical & Biotech Services
Medical Devices Extractables &
Leachables
Markets
» Pharmaceutical Packaging Industry
» Pharmaceutical Industry
» Biotech and Diagnostic Industry

7. 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

8. GROWTH LABORATORY ACTIVITIES - EU

9. 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)

10. Quality Credentials
System/Authority Europe USA
ISO 17025:2005 √ BELAC √ ACLASS
GMP √ FAGG √ FDA
GLP √ WIV √ FDA
FDA registration √ √
AAALAC/MSPCA/OLAW √
NRC √
(radiolabeling studies)
10 CONFIDENTIAL

11. US-laboratories

12. EU-laboratories

13. Proof-of Concept
CONFIDENTIAL

14. 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.

15. 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.

16. Preclincal Toxicology (GLP)
CONFIDENTIAL

17. 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.
17 CONFIDENTIAL

18. 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.
18 CONFIDENTIAL

19. 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.
19 CONFIDENTIAL

20. Analytical Services – material characterization /
Stability (GMP)
CONFIDENTIAL

21. 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

22. THANK YOU!