Biomedical Research Models, Inc. (BRM) is a biomedical research company located in Worcester, MA that offers pre-clinical research services (CRO/Contract Research Organization) to the health industry. From early discovery to early toxicology New Drug Application (NDA), BRM is able to conduct in vivo phases of nonclinical programs including: pharmacokinetics; in vivo lead compound screening; proof of concept; efficacy assessment; pharmacology; mechanism of action; early lead optimization toxicology; as well as provide supportive colony maintenance and on-site client room use agreements.

1. Biomedical Research Models, Inc.
Contract Discovery and Preclinical Research

2. What Makes Us Different
• Scientific Reputation and Expertise
◦ $20M+ in United States Public Health Service
Grants/Contracts
◦ Preclinical Testing Contract for Type 1 Diabetes
• Model Development
• IP- Proprietary Animal Models
◦ Metabolic and Autoimmune Diseases
• Colony Management and Dedicated
Use Agreements
◦ Favorable Discovery Model
• Focused on Helping Nominate
Drug Candidates for Development

3. Biomedical Research Models, Inc.
• Established in 1996
• OLAW assured - 1999
• AAALAC accredited - 2006
• USDA Registered - 2008
• Worcester, MA location~45 FTEs

4. Areas of Expertise
Autoimmune Diseases Neuro-Degenerative Diseases
• Type 1 Diabetes • Multiple Sclerosis
• Lupus • Diabetic Neuropathies
• Rheumatoid Arthritis • Diabetic Encephalopathies
• Multiple Sclerosis • Alzheimer Disease
• Amyotrophic Lateral • Amyotrophic Lateral Sclerosis
Sclerosis
• Inflammatory Inflammation and Pain
Bowel Disease • Delayed-type hypersensitivity
• Rheumatoid Arthritis
Metabolic Diseases • Inflammatory Bowel Disease
• Type 2 Diabetes • Osteoarthritis
• Metabolic Syndrome • Wound Healing
• Obesity
• Dyslipidemia Virology
• Renal Models • Virus Infection Models
• Vaccines/Antiviral

5. Proprietary Rat Models:
Diabetes
• BioBreeding Diabetic Prone (BBDP/Wor) Rat
◦ > 85% spontaneous incidence of Type 1 Diabetes (T1D)
◦ Diabetic complications including
neuropathies, retinopathy and encephalopathy's
(cognition)
• BioBreeding Zucker Diabetic Rat (BBZDR/Wor)
◦ Males develop obesity & Type 2 Diabetic (T2D)
• Similar to ZDF, plus inbred and hypertensive
• Develops diabetic complications including:
retinopathy, neuropathy, atherosclerosis and
end stage renal disease (ESRD)
• Alzheimer’s disease
◦ Females develop obesity and Metabolic Syndrome

6. Proprietary Rat Models:
Autoimmune Diseases
• BioBreeding Diabetic Resistant (BBDR/Wor) Rat
◦ T1D controls (0% T1D incidence in VAF housing)
◦ Inducible Autoimmunity
• Viral Induced Autoimmunity (VIA)
• TLR modeling
• Rheumatoid Arthritis (RA)
• Multiple Autoimmune Disease (MAD) Rat
◦ 2010 Awarded NIH grant to characterize IBD, RA
◦ ~2-3% spontaneous incidence of T1D
◦ VIA by β herpes virus or parvovirus
◦ TLR modeling
• WAG.rnu
◦ Aythmic nude rat
◦ Used for transplantation and adoptive transfer
◦ “Super nude” via proprietary treatment

7. Colony Management
• Genetic rodent capabilities
◦ Mating & breeding
◦ PCR genotyping / RT PCR
◦ Quarantine rederivation
◦ Embryo transfer & cesarean rederivation
◦ Procedural manipulations
◦ Pharmacology & toxicology
• Semi-rigid isolator animal housing
• In vitro Laboratories

8. Discovery Research
High Throughput-Customized Screening
• Species: mouse, rat, guinea pig, rabbit, dog, marmoset
• Small molecule, peptide, proteins and
cell-based products
• In vitro and ex vivo assays
• Acute, repeat dosing and infusion
• PK/PD parameters (non-compartmental and compartmental)
• Fluid collections (blood, urine, CSF, etc…)
including microdialysis
• Dose linearity and tolerability
• Abbreviated protocol
• One-week turn around time

9. Discovery Toxicology
• Non-GLP
◦ Discovery and early development support
◦ Dose-ranging finding
◦ Dose escalation and tolerability
◦ Drug exposure
• Acute single dose, 7 or 14 days
• Chronic dose, 7 – 14 days
• Clinical pathology and chemistry
• Gross necropsy with limited or extensive
histopathology

10. Laboratory Services
• Tissue culture and cell line maintenance
• Serological and immunochemistry analyses
• Immunoassays (ELISA, EIA)
• Histology and immunohistochemistry
• Flow cytometry/FACS Analysis
• PCR/Real time PCR
◦ DNA/RNA extraction
• Fluid analysis
◦ Blood
◦ Urine
◦ CSF
◦ Tissue homogenization
◦ Cell isolation

11. Credentials
Publications
• Tikhonenko M. et al., 2013. N-3 polyunsaturated Fatty acids prevent diabetic retinopathy by inhibition
of retinal vascular damage and enhanced endothelial progenitor cell reparative function. PLoS One.
8 (1):e55177. Epub 2013 Jan 29.
• Christian W. Grant et al., 2012. Development of Standardized Insulin Treatment Protocols for
Spontaneous Rodent Models of Type 1 Diabetes. Comparative Medicine. 62: 381-390.
• Mordes JP, Bortell R, Guberski DL, Rossini AA, Greiner DL. Autoimmune diabetes mellitus in the BB rat.
In: Sima AAF, Shafrir E, eds. Frontiers in animal diabetes research, Primer on animal models of diabetes.
Reading, UK: Hardwood Academic Publishers; 1-41.
• Yang K, Whalen BJ,, Tirabassi R, et al., A DNA vaccine prime followed by a liposome-encapsulated
protein boost confers enhanced mucosal immune responses and protection. J Immunol. 2008 May
1;180(9):6159-67.
Presentations
• Christian W. Grant, Lisa M. Spain, Catherine Moran-Paul, Shane Duclos, Dennis L. Guberski, Guillermo
Arreaza-Rubin. Results From The NIDDK Preclinical Testing Program For Prevention and Reversal of
Type 1 Diabetes. Focis 2012
• Christian W. Grant, Catherine Moran-Paul, Shane K. Duclos, Rebecca S. Tirabassi1, Lisa M.
Spain, Guillermo Arreaza-Rubin, and Dennis L. Guberski. Increased severity of insulitis without
decrease in beta cell mass in pre-diabetic non-obese diabetic (NOD) mice with impaired glucose
tolerance. QUAD 2012
• Barak Yahalom, Barbara Whalen, Maria L. Pedersen, James E. Staruk, Christian W. Grant, and Joan F.
Flanagan. Validation of a Reproducible Animal Model for Crohn’s Disease. IRA 2012
• Kari E. Harbert, Melissa M. Haskell, DVM, and Alain Stricker-Krongrad, Ph.D. Using the Conscious
Guinea Pig to Evaluate human Ether-à-go-go Related Gene (hERG) Channel Blockers. QUAD 2012