Over 50 years of Scientific Excellence

AAALAC Accredited

GLP Service Provider

Chicago, IL

US based research institute and nonclinical CRO, Chicago, IL

Over 110 full-time staff, greater than one third with advanced degrees

Staff tenure averages 10.4 years

Study director tenure averages 18+ years

Highly experienced, skilled and tenured animal technicians Published team of experts in their respective fields Onsite veterinary, clinical pathology, histopathology

Comprehensive nonclinical services portfolio with niche expertise

High volume of repeat work

Government, academic, and commercial sponsors ◦ Internal grant and contract writing team ◦ Grant writing support and collaborations

Complete nonclinical testing and development services

Drugs, vaccines, biologics, nutraceuticals, biopesticides

Regulatory expertise in EPA and FDA guidelines ◦ Regulatory support

Extensive capabilities in inhalation and aerosol sciences

Multiple species capabilities and experience ◦ Rodent, rabbit, guinea pig, ferret, nonhuman primate, canine, mini-pig

Specialized animal models o Oncology, infectious disease, respiratory, wound

Robust bioanalytical capabilities, preclinical-clinical

Complete micro and molecular biology capabilities

Located in Chicago, IL

Over 125,000 square feet

ABSL/BSL 2-3

Small and Large Animal Facilities

Surgical Suites

Xenograft Isolation Facilities Inhalation Suites for small and large animals

Analytical Chemistry Laboratories

Micro-Molecular Biology Laboratories

Over $20 million invested in last 7 years

AAALAC Accredited

OLAW Assured

Good Laboratory Practice

ICH/OECD Compliant Select Agent Registered

DoD Security Clearance

Active US Army Biosurety Program

ABSL-BSL 2/3

In Vivo Pharmacokinetics and ADME , including radiolabeled ◦ Method development and validation

Genetic Toxicology : mutagenesis, cytotoxicity, chromosomal damage ◦ Ames Assay ◦ Micronucleus Assays, in vitro and in vivo ◦ Comet Assays ◦ Neutral Red Cytotoxicity Assay ◦ Mouse Lymphoma Assay ◦ Structural Chromosome Aberration Assay

Cell Lines: CHO, HPBL, CHL, V-79

Safety Pharmacology: Core Battery Assessment ◦ Cardiovascular Physiology: Telemetry ◦ CNS Function: Neurobehavioral Assessment ◦ Respiratory Physiology: Plesmography ◦ Rodent, Canine, Guinea pig, Nonhuman Primate

Systemic Toxicology including Aerosol Dosing ◦ Experience with a wide range of administration routes and methods ◦ All technicians have 5 or more years experience and BS/MS degrees ◦ Rodent, rabbit, guinea pig, canine, nonhuman primate, mini-pig

Immunotoxicology ◦ ELISA Development ◦ Detection of Cytokines ◦ Plaque Forming Cell Assay ◦ Natural Killer Assay ◦ In Vivo Host Defense Models ◦ Murine Local Lymph Node Assay ◦ Lymphocyte Blastogenesis Assay ◦ Cytotoxic T-lymphocyte Assay

Complete Analytical Chemistry Services

Complete Molecular and Microbiology Services

Smooth transition to Phase I ◦ method cross-validation and early clinical PK-TK analysis

Early clinical phase PK-TK sample analysis

Chronic Toxicology ◦ 6-9-12 month studies

◦ Rodent, rabbit, guinea pig, canine, nonhuman primate, mini-pig

Developmental and Reproductive Toxicology ◦ Rodents, rabbits

Carcinogenicity ◦ 1-2 year studies

Nonclinical: Complete Assay Development and Validation

◦ Pharmacokinetics and ADME

◦ Drug metabolite profiles

◦ Biomarker identification

◦ Protein binding

◦ Tissue and fluid drug concentrations

◦ Drug-drug interactions

◦ In vitro metabolism

◦ Extractables and leachables

Extensive expertise in small molecule trace level analysis ◦ Gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS)

Extensive expertise in elemental trace level analysis ◦ Inductively coupled plasma -mass spectrometry (ICP-MS)

Clinical: Smooth transition from pre-IND to Phase I: 30 days ◦ Cross validation of preclinical PK methods for clinical use

◦ Early clinical PK-TK sample analysis

Biographies and publications available

Types of Studies PK and ADME

Toxicology

Pulmonary sensitization

Sensory irritation

Lung inflammatory studies

Expertise Generation of complex mixtures of vapor/particulate atmospheres

Generation and monitoring of nanoparticles

Generation of viable aerosols

Modeling of pulmonary deposition

Custom designs for dispersion of powders, liquids and mixtures

Pulmonary function measurements

Aerosol Generation Systems Nebulizers, Spray nozzles, Powder dispersion Custom designed systems

Aerosol Atmosphere Monitoring Systems Aerosol concentration Particle size distribution Gas concentration Chemical analysis

Respiratory Disease Models Asthma COPD Pulmonary fibrosis Lung cancer

IITRI Process and System Bacterial cells are diluted with PBS to specified concentrations

◦ Osmolarity of cells is maintained ◦ Washing of cells is unnecessary

Six simultaneously firing nebulizers require less pressure ◦ Lower pressure - less cellular shearing = higher viability ◦ Lower pressure - less foaming - no antifoam = higher viability

100% humidified air provided to animals without dilution air ◦ Higher humidity – less desiccation = higher viability ◦ No dilution air – higher humidity = higher viability

Benefits of IITRI System High-efficiency delivery of viable microorganisms

High accuracy for delivery of specified doses

Biographies and publications available

Starting culture concentration (CFU/mL)

1e+6 1e+7 1e+8 1e+9

1e+6 1e+7 1e+8 1e+9

Sp

ray F

ac

tor

(Fs)

1e-10

1e-9

1e-8

1e-7

1e-6

1e-5

1e-4

1e-3

1e-2

1e-1

1e+0

1e-10

1e-9

1e-8

1e-7

1e-6

1e-5

1e-4

1e-3

1e-2

1e-1

1e+0

Comparison of Spray Factor with Multiple Concentrations

Infectious Disease Model Development

Vaccines, anti-bacterials, anti-virals ◦ Immunogenicity, Efficacy, PK, Safety-Toxicology ◦ Various dosing routes including aerosol ◦ BSL2-3

Influenza experience specifically

◦ Ferret and guinea pig models, transmission models ◦ Multiple seasonal influenza strains, H3N2 and H1N1 ◦ Pandemic H1N1 and H5N1 strains including highly pathogenic H5N1

Extensive Pathogen and Toxin Library Evaluation of decontamination materials Validation of bio-detection methods

Microbiology

◦ ELISAs

◦ Hemagglutination inhibition assays

◦ Viral neutralization assays

◦ Bacterial/viral extraction and isolation

Molecular Biology

◦ Real-time, quantitative PCR

◦ Microbial forensics

◦ Gene expression, cloning and DNA sequencing

◦ Biomarker identification and detection

Biographies and publications available

IITRI is the largest nonclinical contractor to the NCI ◦ Screening ◦ Efficacy ◦ Pharmacokinetics ◦ Full safety testing, toxicology

Cancer Biology: In Vitro and In Vivo Studies ◦ Mechanism of action ◦ Drug-drug interactions ◦ Drug concentration in tissues ◦ Gene expression, cloning and DNA sequencing ◦ Well established xenograft models ◦ Development of new xenograft models ◦ Highly experienced in the testing of natural compounds ◦ Growth initiative: orthotopic model development

Biographies and publications available

IITRI and EPA, 1985-1994 ◦ Cooperative agreement with EPA ◦ Assessment of toxicity and pathogenicity testing methods and protocols ◦ This work markedly changed FIFRA, now OPPTS guidelines

Well-versed in US and Canadian guidelines Member of the Biopesticide Industry Alliance

Complete Safety and Pathogenicity Testing

◦ Acute eye irritation ◦ Acute dermal irritation ◦ Skin sensitization ◦ Dermal toxicity and pathogenicity ◦ Injection toxicity and pathogenicity ◦ Pulmonary toxicity and pathogenicity ◦ Oral toxicity and pathogenicity ◦ Reproductive toxicity ◦ Immunotoxicity ◦ Storage stability

Biographies and publications available

Incision Site Wound: topical treatment ◦ Models surgical site wounds and cuts, various bacteria

Groin Wound: topical treatment ◦ Models MRSA (or other) SC infection with sepsis

Deep Puncture Thigh Wound: topical, injectable, PO ◦ Models deep puncture wound often leading to sepsis

Peritonitis Wound, two types ◦ Caecal ligature and puncture: to assess direct site treatment

◦ IP injection of bacteria: to assess surgical gels used internally

Scientific excellence since 1936

Highly experienced, tenured and published team

Hands on study directors for personalized attention

Technical expertise for a variety of complex and diverse programs

Fully integrated nonclinical developmental services

Many long-standing industry relationships including co-authored work

Applied regulatory expertise in support of full program development

Robust analytical capabilities to support nonclinical and early clinical studies

From grant writing support to development, efficacy and safety testing, IITRI supports all your nonclinical in vivo and analytical needs at a single US facility.

Jessica Humphreys, BSN

717-467-5186 717-668-3133

www.linkedin.com/in/jessicahumphreys jhumphreys@iitri.org

www.iitri.org