Complete Target-to-Clinic Capabilities€¢pls...immune disorders, rare orphan diseases, and ophthalmology Animal Welfare Be sure to ask us about our comprehensive animal welfare program,

CompleteTarget-to-ClinicCapabilities

Providing early-stage drug and device research options for more than 20 years.

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MPI Research Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .3

Anatomic and Clinical Pathology . . . . . . . . . . . . . . . . . . . . . . . . . . .4

Clinical Bioanalytical Analysis for Biologics . . . . . . . . . . . . . . . . .6

Clinical Research . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .8

Developmental and Reproductive Toxicology . . . . . . . . . . . . 10

Drug Metabolism and Pharmacokinetics Research . . . . . . . . 12

General Toxicology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14

Infusion Toxicology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16

In Vitro Research . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18

In Vivo Research . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20

Molecular Imaging and Radiochemistry . . . . . . . . . . . . . . . . . . 22

Neurobehavioral Sciences . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24

Nonclinical Dose Formulation and Analysis . . . . . . . . . . . . . . . 26

Nonclinical Ligand Binding Assays . . . . . . . . . . . . . . . . . . . . . . . 28

Safety Pharmacology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30

Small Molecule Clinical Bioanalytical Analysis. . . . . . . . . . . . . 32

Small Molecule Preclinical Bioanalytical Analysis. . . . . . . . . . 34

Surgical Efficacy and Medical Device Evaluation . . . . . . . . . . 36

Targeted Delivery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38

MPI Research Solutions

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Peace of Mind

MPI Research insists on the highest quality professional standards across all services and at all levels, and is in full compliance with international, federal, and state regulatory agencies. We are

•FullyAAALACaccredited

•IncompliancewithallFDA,EPA, EMEA, OECD, ICH, and JMHW guidances and regulations

•Dedicatedtoqualityperformanceand continuous improvement, with registered QA professionals (RQAP-GLP) and on-staff Lean Six Sigma Blackbelts

•Continuallyconductinginspections of GLP and Bioequivalence studies and reports

•Committedtoconductingongoingoperational and subcontractor audits

Valuable Resources

Sponsors appreciate the wide array of assets and resources that are available at MPI Research, including

•Anextensiveandrobusthistoricalcontrol database

•Aknowledgeablestaffthatisexperienced with all types of test articles, including small and large molecules (recombinant proteins, antibodies, and vaccines), food additives, veterinary compounds, synthetic organic chemicals, pesticides, and petrochemicals

•Standardandspecializedanimalmodels, including rodent, canine, nonhuman primate, swine, rabbit, and feline, and naïve and non-naïve standing colonies of a variety of species

•Opportunitiestoestablishstock animal colonies for quick starts of in-life studies

•A50-bedPhaseIclinicforearlyclinicaldevelopment and bioequivalence trials

•Aggressivereportingtimelines

•Asecurechain-of-custodymanagement and verification system for all test materials

•Scientificexpertsinmanydifferenttherapeutic areas, including oncology, neurology, infectious disease, cardiology, metabolic disorders, inflammation, orthopaedics, renal, immune disorders, rare orphan diseases, and ophthalmology

Animal Welfare

Be sure to ask us about our comprehensive animal welfare program, which includes a dedicated IACUC staff, a post-approval monitoring program, social housing in multiple species, an animal adoption program, and a company employee recognition program related to the care and well-being of our animals.

Embrace the future. Contact us to learn more at [email protected].

Envision a Partner with MoreMPIResearchisafulldrugdevelopmentcontractresearchorganizationwiththeworld’slargestsingle-sitepreclinicalfacility.OurSponsors benefit from our full suite of preclinical and clinical research services allowing for proof-of-concept and first-in-human studies.

Our Sponsors value our collaborative culture that is uniformly committed to helping them move their compounds from bench to regulatory filing with accuracy, quality, and speed. Our experienced staff is flexible in adapting to changes and quickly responds to challenges as they arise.


Anatomic Pathology/Clinical PathologyThe pathology discipline frequently lies at the center of effective preclinical product research and development. Experts in the pathology discipline provide key information on anatomical and clinical pathology-related effects of products and interpreting the biologic and toxicologic significance of these effects for Sponsors and regulators. The accurate assessment and interpretation of pathology endpoints from preclinical animal models is an essential component for establishing the safety profile for clinical development and product registration.

MPI Research performs integrated and comprehensive pathology evaluations by an experienced team of board-certified veterinary anatomic and clinical pathologists. Our highly trained technical and support staff ensure the accurate collection and processing of specimens with efficient reporting of data while maintaining the flexibility to adapt as needs evolve.

Service Highlights

MPI Research is experienced, knowledgeable, and ready to meet your needs by providing

•GLP-compliant,fullyintegrated, on-site laboratories for clinical pathology, necropsy, tissue trimming, and histology with a wide range of pathology services to support your needs

•Accessible,highlyqualifiedpathologyprofessionals who respond to novel, specialized,orchangingneedsquicklyand efficiently

•Robustmulti-specieshistoricalcontroldatabase for anatomic and clinical pathology endpoints

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•Experiencewithtraditionaland novel animal species/models ranging from conventional preclinical species in routine and non-routine study design to nonconventional test species and livestock

•IntegratedProvantis™systemplatformfor rapid, accurate data capture, entry, and reporting

•AperioScanScope®scanners andSpectrum™DigitalPathologySystem for brightfield or fluorescent whole-slide scanning and histomorphometry analysis

•Securechain-of-custodymanagementand verification of all specimens

•DiscoveryandGLP-compliantfulldevelopment studies

•Highlyexperiencedconduct and reporting of rodent carcinogenesis studies

Anatomic Pathology

High-quality anatomic pathology evaluations and reporting are key components in the safety assessment of your compound, device, or combination product. The MPI Research pathology teamincludesoneoftheworld’slargestcollections of experienced, board-certified veterinary pathologists working as an effective team within a single site preclinical CRO. Our on-site team of pathologists has broad experience in the toxicologic pathology community and actively share the garnered experiences to ensure pathology assessments for studies are appropriate and aligned with industry standards. The extensive collective knowledge of the team and the broad experience with a wide variety of compounds (small molecules and biologics), animal models, and study designs—can offer you the peace of mind that evaluations are appropriate,

complete, and accurate for the various stages of product development (early discovery through full development). Our goal is to become your effective partner in developing your product. We can provide pathology consultation during all stages of development toensureSponsors’needsareappropriately addressed in cost efficient design and conduct of studies programs. We use SEND compliant terminology and methods to address evolving regulatory requirements.

As part of our commitment to high-quality pathology assessments/reports, we have been long-time advocates and providers of pathology peer review. Special anatomic pathology services can also be provided for specific study needs, including morphometric, electron microscopic, and immunohistochemical assessments. We are networked with a large contingent of consultant and pathology specialists who can provide highlyspecializedassessmentswhennonconventional needs arise and will facilitate appropriate specimen collection, tissue preparation, specimen shipment, and reporting strategies for your development needs.

Trimming and Histology

•High-throughputcapacityforrapidproduction of high-quality specimens (capabilities to process over 2 million tissues annually)

•Paraffinandfrozentissueprocessingand slide preparation for routine, specialized,anddiagnostic microscopic examination

•Immunofluorescenceandimmunohistochemical techniques (85+validated)

•Specialstainingprocedures (60+validated)

Necropsy

•On-sitenecropsysupervisionbyaboard-certified veterinary pathologist

•High-capacity,multi-species gross pathology facility with dedicated individual small and large animal workstations

•Routineandspecializedproceduresincluding– Whole-body and upper body

perfusions– Perilymphatic perfusions of inner

ear for ototoxicity studies– Harvesting and isolation

of eye structures– Harvesting and isolation of

structures of the central and peripheral nervous systems

– Specializedtissuecollectionforspecial procedures including electron microscopy, qPCR, or mRNA analyses

•Specializeddigitalimagingequipment

Clinical Pathology

MPI Research offers a complete array of traditional clinical pathology endpoints and state-of-the-art biomarker capabilities to support a wide range of investigational studies. GLP-compliant validation and quality control measures ensure that data of the highest quality are generated and accurately reported.

•Hematology

•Clinicalchemistry

•Coagulation/plateletcharacterization

•Urinalysis

•Immunoassays/biomarkers

•Fluidanalysis

•Bloodgasanalysis

•Bonemarrowevaluation

•Cytopathology

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Clinical Bioanalytical Analysis for BiologicsThe human body is remarkable in its ability to wage war against a host of diseases and infections. Understanding the immune system’sarsenalprovidesvaluableknowledgethatdrivessomeofthelatestinnovationsindrugtherapy,especiallyinbiologicallyderived medicines and vaccines. MPI Research understands that proper assessments, along with scientific and regulatory expertise, are paramount in advancing your biologic studies.

MPI Research has developed and validated more than 300 bioanalytical methods for biologics over the past five years. These methods have been validated for the analysis of drugs in plasma, serum, urine or CSF, which include TK/PK, immunogenicity, NAb, and biomarker assays. All methods were validated in accordance with FDA and European Medicines Agency (EMA) guidelines for bioanalytical method validation.

MPIResearchofferscustomizeddevelopment and validation of bioanalytical methods for the detection and quantification of biologics with a wide range of molecule types, including monoclonal therapeutic antibodies, enzymes,proteins,peptides,andoligonucleotides.


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Service Highlights

Bioanalysis of protein therapeutics can be performed using

•Enzyme-linkedimmunosorbent assay (ELISA)

•Homogenoustime-resolvedfluorescence

•Electrochemiluminescence(MSD)

•GyroLab

•Bead-based(e.g.,Luminex)platforms

Speed and Capacity

MPI Research offers comprehensive bioanalytical and pharmacokinetic services for Phase I first-in-human trials and biosimilar programs. Specifically, with our clinic, MPI Research can provide timelines for clinical summary reports inasfewas25daysfromcriticalreagentavailability. Our standard timeline for method development and validation of a protein therapeutic is five weeks. Our routine timeline for sample analysis is 10 days for audited data.

The critical components to achieve these milestones are streamlined workflow processes with a comprehensive training program and a proprietary LIMS with advanced data management and publishing capabilities.

Current Resources

•ELISAmicroplatereaders

•MesoScaleDiscovery(MSD)SectorImager 6000

•Gyrosworkstations

•Bioplex200(Luminex)platform

•PerkinElmerliquidhandlingsystems for automated sample preparation

•TissuesamplepreparationusingCovaris AFA ultrasonic extraction instruments, equipped with cryogenic pulverizationofhardtissues

•ThermoWatsonLIMS™systemfordatamanagement and reporting

•ProprietaryExyLIMSsystemforsampleand data management

•Centralsecurityalarmmonitoringsystem with 24-hour card-controlled facility access

•On-siteemergencypowerbackup forallsamplestoragefreezers (-20°C, -70°C)

•Freezertemperaturemonitoringwithremote notification capability

•ACpowerfailuremonitoringsystemswith immediate notification capability

•Incrementalnightlydatabackupsandfull weekly and monthly backups

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Clinical ResearchJasperClinicoperatesa50+bedunitintheheartofadiversebiomedicalcommunitythathoststop-notchhealthcare(includingaLevel 1 trauma center adjacent to the clinic), life science and medical device research firms, a comprehensive cancer center, and medical school. Our staff has broad scientific expertise across a range of therapeutic areas. We also use up-to-date clinical technology and offer on-site recreation and support services for our study participants.

Our clinical solutions allow Jasper Clinic to partner with Sponsors to advance the clinical development of drugs and devices.

Therapeutic Experience

•Anti-bacterial

•Anti-viral

•Diabetes

•CNS

•Anticoagulant

•Inflammation

•Obesity

•Lipidlowering

•Cardiology– Congestive heart failure

•Pain

•Ophthalmology– Glaucoma– Ocular hypertension– Macular degeneration– Retinal

•Oncology– Non-cytotoxic– Limited patient types

•Dermatology/skincare– Punch biopsy– Gene expression

•Treatmentsforrenaldisease

•Womenshealth– Fertility – Sexual dysfunction


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Types of Studies

•First-in-human– SAD– MAD– Adaptive

•Druginteraction(simpleandcomplex)

•Proof-of-targetengagement

•Proof-of-concept,methodology

•Biomarkervalidation

•Pharmacogeneticdesigns (controlled and stratified)

•Bioavailability/bioequivalency(BA/BE)– Absolute and relative– Pilot and pivotal

•Foodeffect

•Gendereffect

•Ageeffect

•Cognition

•Alcoholinteraction

•Translationalscience(Phase0)

•PhaselcomponentsofPhasell and lll Studies

Pharmacy Schedule

•Clinicalsupplypreparation– Over encapsulation– Sterile dosage forms– Powder in capsule

•ScheduleII-V

Cardiac Safety, QT Studies

•24bedsondigitalcardiactelemetry

•ThoroughQTc

•Holtermonitoring

•ExperiencedECGprovidersfor ECG over-read services

Biomarker Support

•GenomicDNAisolation

•Genotyping

•Geneexpression/bloodtissue

•Rigorousclinicalsampling

•Biomarkervalidation– Safety markers– Efficacy markers

•Knownandnoveltargets

Biomarkers, Genetics, Imaging

•Genotypedvolunteers

•Rapidgenotypingservices

•Specializedbiomarker sample preparation

•Imagingmodalities– PET– fMRI– X-Ray– OCT– Thermal– Dexa– Other

•Methodology

Clinical Development Plans

•Write-from-scratchprojectplanning

•Feasibilityassessment consultation services

•Optimizationofpreclinical activities leading to IND

•Proof-of-concept/target/design

•PhaseIcomponents in Phase II/III studies

•FDAmeetingsubmissionservices

Protocol Writing

•Studydesignandfeasibilityassessment

•Flexibleformatsandtemplates

Partnered CRF, Data Management

•ElectronicorpaperCRFs


•Databasecreationandwarehousing

•Securedigitalaccesstostudydata

•Direct-to-Sponsordatabaseentry

•Lowqueryrate/fastresolution of data queries

•Speedydatabaselock

•CDISC/CDASHcompliant

PK/PD Analysis

•ValidatedWinNonlin®software

•Experiencedpharmacokineticists

•Fastinterimanalysisandinterpretation– Same day in FIH studies

•ProductionofPKsectionofclinicalstudy reports

Regulatory

•SuccessfulSponsorand FDA inspections– No significant findings or FD-483

•Successfulclientsubmissions

Report Writing

•Interpretationofresults


•Fullreportcompilation

•Manuscriptpreparation

MPI Research SolutionsMPI Research Solutions

Developmental and Reproductive ToxicologyThe need to know how a drug candidate affects reproductive and developmental functions, from fertility to embryonic, prenatal and postnatal development, as well as maternal effects, is an important aspect of drug safety testing. Developmental and reproductive toxicology (DART) testing of chemicals and pesticides, small-molecules, and biologics must be vigorous, comprehensive, and reliable.

Conducting quality DART studies on a vast array of compounds from many different industries is proof-positive of the collaborative expertise at MPI Research. By employing the best and brightest from private and public sectors, we enhance our collective skillset while speaking the language of our Sponsors. We understand their needs, and we dedicate ourselves to meeting them.

MPI Research offers industry-leading study designs, with DART expertise set firmly on the competitive edge. These designsarecustomizedtoindividualSponsor needs aligned with regulatory guidances, including FDA, EMEA, and OECD standards. Our capabilities encompass a variety of species and routes of administration, all aimed at determining the safety and biological effects of compounds.

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Service Highlights

•Fertilityandearlyembryonicdevelopment studies (rodent)

•Pre-andpostnataldevelopmentstudies, including maternal function (rodent)

•Embryo-fetaldevelopmentstudies(rodent, rabbit)

•Neonatalandjuvenileanimalstudies

•Developmentalneurotoxicologystudies

•Toxicokineticevaluation

•Maternalevaluations– Necropsy– C-sections– Uterine examinations

•Post-lifefetalevaluationsinmultiplespecies and strains – External morphology– Visceral– Skeletal

•Neurobehavioralassessments– Motor activity– Learning– Memory– Acoustic startle response

•Spermassessments– Concentration– Count– Motility (using Hamilton Thorne IVOSAnalyzer)

– Morphology

•Acompletesuiteofdevelopmentaland fertility studies in cynomolgus monkeys with all necessary endpoints, including – Monitoring of menstrual

and mating cycles– Dosing and handling

of pregnant females– Use of ultrasound in determining

pregnancy status and collecting key measurements such as fetal Heart Rate [HR], Crown-Rump Length [CRL], Bi-Parietal Diameter [BPD], Femur Length [FL], and other important aspects of fetal evaluation

– C-section– Sperm collection and evaluation– Testes volume measurement– Blood collection to determine

hormone and test article concentration

•In vivo specialty studies for endocrine-disrupting chemicals – Uterotrophic– Hershberger assays– Male and female pubertal assays

•Technicalstaffproficientintest article administration – Oral gavage– Dietary– Dermal– Subcutaneous (including implants)– Intravenous– Intramuscular– Intraperitoneal– Intravaginal– Intranasal– Infusion

•Infantformulatesting(pigletmodel)

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Drug Metabolism and Pharmacokinetics ResearchAttritionratesduringclinicaldevelopmentofnewtherapeuticsareashighas95percent—disturbingnewsforbothpatientsanddrugdevelopers. In addition to failure from efficacy and safety concerns, clinical failures can also be attributed to poor pharmacokinetic (PK) properties. Obtaining early, critical drug metabolism and pharmacokinetic (DMPK) information that can be leveraged in the design and execution of the development plan is the secret to addressing DMPK failures. Companies with solid DMPK-based drug development programs have been able to cut clinical failures that are due to DMPK reasons from 40 percent to 10 percent, a four-fold decrease.

MPI Research knows speed and accuracy are essential factors within DMPK in order to provide an efficient and cost-effective strategy for any drug development program. We have the expertise and experience to ensure your studies are conducted quickly and successfully. Our commitment is to help our Sponsors achieve the best possible clinical success rates. A solid combination of experience, regulatory

knowledge, and capability in biology, toxicology, chemistry, pharmacology, and metabolite identification, are all expert qualities that our scientists bring to fuel meaningful results and studies. Our Study Directors are a part oftheSponsor’steam;theysharethesame dedication to precise data that advances insight early in development, andtheyconsistentlyexceedSponsors’expectations.

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Service Highlights

•Ascientificteam,experienced in both drug development and regulatory strategies

•Largecapacitytoconductin vivo PK, mass balance, excretion, and tissue distribution studies

•Extensiveexperiencewithallrelevantanimal species (mouse, rat, dog, swine, nonhuman primate, etc.)

•Creationandmanagementof Sponsor-owned colonies of animals

•Fullyintegratedbioanalyticalandpharmacokinetic analysis

•BroadNuclearRegulatoryCommission(NRC) licensing for a range of radiolabels and designs

•Customstudiesforabsorption,biodistribution, metabolism, and excretion (ADME)

•Industry-leadinglaboratorysoftwareand data-management tools, and experience with all laboratory species

•RapidturnaroundofPK studies: five days from startup to summary reports

PK

•In vivo studies – Pharmacokinetics (dose-to-data

in 72 hours)– Screening of multiple compounds– Cassette dosing– Dose range finding (DRF) and

maximum tolerated dose (MTD)– Leadoptimization– Bioequivalence– Modeling services using the PhoenixWinNonlin®platform

ADME

•In vivo studies with or without mass-balance– Pharmacokinetics and

pharmacodynamics– Tissue distribution– Rates and routes of excretion– Biliary excretion and

hepatobiliary recirculation– Animals (rodents, dogs, and

nonhuman primates) surgically prepared for vascular access and bile collection

•Biodistributionmodalities– Traditional dissection and analysis– Quantitative Whole-Body

Autoradiography (QWBA), traditional two-dimensional and three-dimensional

– Positron Emission Tomography (PET)– Single Photon Emission

Tomography (SPECT)

•Metaboliteidentification– Radiochromatographic profiling andUVorMSmetaboliteprofiling

– High Performance Liquid Chromatography(HPLC)withUVandflow-through radioactivity detection

– Structure elucidation of major metabolites

– ThermoLTQOrbitrapDiscovery™high-resolutionandAPI5000tandem mass spectrometers (MS)

•In vitro metabolism – Protein binding– Metabolite profile and

metabolite identification

° Enzymes,cellfractions(microsomes), cells (hepatocytes), tissues, and in situ preparations

– Reactive metabolites– Stability in microsomes, S9 fraction,

and/or hepatocytes

– Plasma/whole blood partitioning– Elucidation of metabolic pathways– Drug-drug interaction (DDI) studies

(if needed)

° CYP activity profiles, CYP inhibition and induction

° Non-CYP metabolism– Permeability and drug transport

(influx and efflux)

•In vitro transporters– Permeability– Inhibition– Substrates

•In vitro binding– Whole blood partitioning– Plasma binding– Tissue binding

•In vitro toxicity– CellCiphrPremier®– eCiphr®cardiovascular– eCiphr®neurological– Ocular irritation– Skin irritation, absorption, andsensitization

•In vitro gene regulation– Gene induction

•Specialtystudies– Dermal penetration

in multiple species– Melanin binding determination

in Long-Evans rats and Dutch- Belted rabbits

– Dosimetry and preparation of dosimetry memo to support human clinical ADME studies

– Full ocular tissue distribution determination by dissection in multiple species

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General ToxicologyRegulatoryagenciesrequirethatSponsorsunderstandthepotentialrisksfortheirproducts;muchofthatinformationcomesfromgeneral toxicology studies. The foundational role of toxicology is to define the effects of a substance on a living organism, including symptoms and mechanisms of action. As the breadth of compounds in development grows more diverse, toxicology studies are becoming increasingly complex.

Relational science is how MPI Research describes its devotion to regulatory standards while maintaining a close collaborative relationship with our Sponsors. Our toxicology experts understand the crucial importance of accurate results, and they share ourSponsors’goalstoattainpositiveoutcomes. Known for our exceptional background with small molecules, our Sponsors gain further peace of mindwhentheyrealizeourextensiveexperience with biopharmaceuticals and biosimilars. With the data in hand, MPI Research takes partnerships to another level by providing insight and counsel on the next steps to take in the drug development process.

MPI Research encompasses both the legacy and the foresight to meet the drug development challenge. Our general toxicology Study Directors have more than 4,000 toxicology studies under their collective belt. They apply their wealth of knowledge collaboratively, working across all functions, to design studies that meet the specific needs of our Sponsors. Detailed evaluation, expert interpretation, and fast turnaround assure Sponsors the best data to drive decisions. When our Sponsors succeed, we succeed.

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As the drug development process has evolved, so has the nature of general toxicology studies. These studies are far from simple and require the involvement of scientific and technical staff from a multitude of disciplines. To withstand the scrutiny of regulatory review, Sponsors need to have confidence in the design, conduct, and interpretation of their general toxicology studies.

Service Highlights

•DirectaccesstoStudyDirectorsthatuse a consultative approach with Sponsors to develop a program tailored to their specific needs

•Anopen,collegialrelationshipwiththe Study Directors across all service areas, allowing Sponsors to leverage their knowledge in multiple disciplines, and ensure study design and data interpretation are accurate

•Theabilitytoincorporatesafetypharmacology, immunology, and clinical pathology endpoints into toxicology study designs to address the unique needs for a variety of therapeutics being developed

•Currentregulatoryknowledgeof the100+guidancedocumentsissuedbyICH,CDER,CBER,CVM,EPA,EMEA,and other regulatory agencies

•Formulationandbioanalyticalmethodand complete toxicokinetic analysis conducted on-site, allowing for real-time communications regarding the data generated from these analyses

•Constantcollaborationwithcolleaguesin bioanalytical/analytical sciences, immunology, pathology services, and other disciplines for comprehensive and consistent results

•Detailedevaluation,interpretation,and fast turnaround of pathology data by on-site, board-certified clinical and anatomic veterinary pathologists

•Anextensivehistoricalcontroldatabase for acute, subchronic, and chronic toxicology studies, as well as carcinogenicity studies

•Pilot/leadoptimization

•Acutestudies

•Subchronicstudies

•Chronicstudies

•Carcinogenicitystudies

Diverse Animal Models

•Rodents

•Canines

•Nonhumanprimates

•Swine

•Rabbits

•Guineapigs

•Ferrets

•Felines

Routes of Administration

•Oral– Gavage– Dietary– Capsule/tablet– Drinking water

•Dermal

•Intradermal

•Parenteral– Intramuscular– Intraperitoneal– Intravenous– Subcutaneous

•Ocular

•Sublingual

•Intravaginal

•Rectal

•Intranasal

Advanced Electronic Data Support

•Integrated,company-wideProvantis™system for efficient and accurate data capture and reporting– In-life– Clinical pathology– Necropsy– Histopathology– VeterinaryManagement System(VMS)

– NextDocs full standard for the exchange of nonclinical data (SEND) package production

Experience with a Wide Variety of Compounds

•Smallmolecules

•Recombinantproteins,antibodies,peptides, other biopharmaceuticals

•Vaccines

•Foodadditives

•Veterinaryproducts

•Industrialchemicals

•Agrochemicals

•Nanoparticles

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Infusion ToxicologyThe curve of advancements in infusion technology is progressing and rapidly advancing new equipment, more routes of administration, targeted tissue dosing, and increasingly complex routines. With greater capabilities come bigger demands for relevant knowledge and proficiency.Skillfullyapplyingadvancedtechnologies,customizedstudies,andexceedingexpectationsinquality,speed,accuracy,andcost-effectiveness, MPI Research offers the competitive edge that Sponsors need.

With solid infusion toxicology capabilities, the experts at MPI Research provideSponsorswithcustomizedstudies, extensive experience, and robust models. Doing so forges a strong partnership that many Sponsors find indispensable as they move their candidate along the drug development pathway. We are committed to assisting our Sponsors to make a difference in people’slives.

MPI Research offers industry-leading infusion toxicology capabilities and conducts studies across a variety of study designs. Our expert infusion team partners with Sponsors to support the development of their drug and to evaluate their needs to design the most appropriate, logistically feasible model for their infusion toxicology programs.

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Service Highlights

•Extensivecapabilitiesininfusiontechnology, supported by knowledge and experience

•Dedicatedscientificandtechnicalstaff

•Routineevaluationofstudiesbyboard-certified pathologists experienced in recognizingbackgroundpathologiesinherent to infusion models

•Robustmodelsthatallow design flexibility – Ambulatory infusion– Jacket-tether infusion– Peripheral percutaneous infusion– Multi-channel infusion

•Infusionmodelsinmultiplespecies– Rodents– Canines– Rabbits– Swines– Nonhuman primates (including

infant primates)

•Long-terminfusioncapabilities

•Dedicatedsurgicalsuiteand support for small and large animal infusion procedures

•Experiencedveterinaryandsurgicalstaff, including surgeons certified by the Academy of Surgical Research

Advanced Electronic Data Support

•Integrated,company-wideProvantis™system for efficient and accurate data capture, entry, and reporting– In-life– Clinical pathology– Necropsy– Histopathology

Experience with a Variety of Compounds

•Recombinantproteins,antibodies,peptides, other biopharmaceuticals

•Largeandsmallmolecules

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In Vitro ResearchThebesttimetodeterminethefateofanewcompoundisearlyinthepipeline.Recognizingthis,MPIResearchhasbuiltrobustcapabilities for in vitro research internally and in partnership with Cyprotex US, LLC. We offer a variety of study designs for discovery and regulatory submission based on current guidance documents.

Our skillset includes molecular, cell-based, and biochemical analyses, broad experience in study designs and techniques, leading-edge technology in a fully equipped cell and molecular biology laboratory, and a host of customizedapplicationsthatdeliverhigh-quality results.

MPI Research applies the highest quality in vitro expertise, from drug discovery through preclinical and early clinical development. By defining efficacy, mechanism of action, metabolism, drug safety, and pharmacokinetics at the test-tube level, we help Sponsors determine which compounds work best—and safely—on the target organ or receptor.

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Service Highlights

•Cellularandmolecularbiologyassays

•In vitro ADME (metabolism, transporters, and binding)

•In vitro toxicology

•In vitro support of in vivo studies– Biomarkers and gene

expression assays– Stem cell research

Cellular and Molecular Biology Assays

•Quantitativereal-timePCR(qPCR)andreverse transcription qPCR (qRT-PCR), GLP capable

•Robotic,fullyautomatedDNAandRNAsample preparation, GLP capable

•High-throughputflowcytometry, GLP capable

•Automated,microfluidics-basedsizingquantification, and quality control of DNA/RNA, and proteins

•Proteinquantificationincluding protein concentration, ELISA, and western blot analysis

•Microplateassaysforenzymeactivitiesand measurement of biomolecules

•Immunofluorescenceassays

•High-resolutiongelmolecularimaging

In Vitro ADME

•Metabolism– Stability– Metabolite identification– CYP inhibition and induction– Non-CYP metabolism

•Transporters– Permeability– Inhibition– Substrate

•Binding– Whole blood partitioning– Plasma binding– Tissue binding

In Vitro Toxicology

•High-contentimaginganalysisforcell proliferation, cytotoxicity, and mitochondria membrane potential

•High-contentimagingfordrug-induced liver injury (DILI)–CellCiphr®premier–CellomicsToxInsightIVTPlatform

•High-contentimagingforcardiovascular and neuronal toxicity– hERG assay, GLP capable–eCiphr®Cardio–eCiphr®Neuro

•Dermalandoculartoxicity– Ocular irritation– Skin irritation, absorption, andsensitization

In Vitro Support of In Vivo Studies (Biomarkers and Stem Cells)

•GLPqPCRorqRT-PCRanalysisoftissue/blood/fluid samples for preclinical vector biodistribution studies in animals and clinical vector shedding studies in human trials– Plasmid- and viral vector-based

therapy– Human stem cell-based therapy– siRNA therapy–Vaccines

•Biomarkerandgeneexpressionstudiesusing qRT-PCR and qPCR arrays

•SingleNucleotidePolymorphism(SNP)genotyping assays

•Cellularimmunologybyflowcytometry–Validatedimmunophenotyping

panels for peripheral blood leukocytes evaluation in various species (rat, dog, nonhuman primate, mouse, and swine)

– Customizedassaydevelopment in advanced applications, such as rare cell quantification and immune function assessment (up to 10 unique cellular parameters simultaneously detected)

•Isolationandcultureofdendriticcellsand Peripheral Blood Mononuclear Cells (PBMCs)

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With emerging technologies and techniques, investment in in vivo research is yielding greater biological insights more efficiently. MPI Research is on the leading edge of this scientific transformation. We are committed to expanding our capabilities and increasing our knowledge so that we can apply the latest tools to this vital step in drug development and safety assessment. These investments benefit our Sponsors and the people who rely on them.

MPI Research brings immense knowledge and expertise to in vivo research. Comprehending the intricacies of this development step, our scientists devote themselves to increasing their understanding of the cellular and molecular processes involved. As we grow in awareness and skill, we apply these assets to our partnerships with Sponsors. Our goal is to work as a team—across functions and with our Sponsors—tomaximizereturnson in vivo research and quickly drive the right decisions.

In Vivo ResearchTestingcompoundsinlivingorganismsisessentialtounderstandinghowthosesubstancesaffectbiology;soessential,infact,that these studies are required and regulated. Whether determining the therapeutic promise of a new medicine or the safety profile of a chemicalcompound,whatresearcherslearnacrossthespectrumofscientifictestingbeforehumanclinicalstudiesmustbeanalyzed at a critical stage: in vivo.

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Cell- and Gene-Based Therapeutic Models

•Surgicaldeliveryofcell-,plasmid-, and viral vector-based test articles to selected anatomic locations (small and large animals)

•Extensiveexperiencewithimmunocompromised rodents

•Tumorigenicity,biodistribution, and safety assessments of cell and DNA-based test articles

Models for Anticancer Drug Discovery

•Molecularimagingcapabilitiesfortestarticle assessment and biodistribution

Metabolic Disease Models

•Streptozotocin(STZ)-induceddiabetes(rodents and yucatan minipigs)

•Diet-inducedandgenetic diabetes (rodents)

•Hypercholesterolemia/atherosclerosis(minipig;geneknockout)

•Highfatdiet/lowdoseSTZ-induceddiabetes (rats)

•Non-alcoholicsteatohepatitis(NASH)

•Glucosetolerancetests,selectedbiomarker analysis

Infectious Disease Models

•Mouseperitonitis(MRSA,MSSA;Streptococcus pneumonia, PRSP, PSSP)

•Chinchillaacuteotitismedia(Haemophilus influenzae)

•Rabbitotitisexterna (Pseudomonas aeruginosae)

•Vaccinesafetystudies(rodents,ferrets,and canines)

•BSL-2laboratoryandvivariumspace

Ocular Disease and Toxicity

•HeidelbergSpectralisimagingplatform (OCT, fluorescein and ICG angiography, confocal scanning laser ophthalmoscopy)

•Rodentcolorfundicimaging(PhoenixResearchLabsMicronIVplatform)

•Largeanimalwide-field,colorfundicimaging (Clarity Medical Systems RetCam Shuttle platform)

•ERG(dark-adapted,light-adapted,flickerresponses,ISCEVstandards)

•Indirectanddirectophthalmoscopy,slit-lamp biomicroscopy, corneal fluorescein staining

•Hackett-McDonaldscoring(andcustomizedscoringprotocols)

•Tonometry(intraocularpressuremeasurements), gonioscopy, Schirmer tear/phenol red thread testing

•Specializedocularadministrationroutes (intravitreal, intracameral, subconjunctival, subtenon, subretinal, as well as topical and systemic dose routes)

•Aqueous/vitreoushumorcollections;detailed ocular tissue dissections for ocular PK/biodistribution determinations

Cardiovascular Models

•Atherosclerosismodelsinavarietyofspecies (denudation and high fat diet)

•Acutemyocardialinfarction(ischemia/reperfusion)

•Congestiveheartfailure

•Chroniccardiacand peripheral ischemia

•Peripheralarterialdisease

•Thrombosismodels

•Surgicalmodels

Inflammation Models

•Collagen-inducedarthritis(rats,NHPs)

•Bleomycin-inducedlungfibrosis(rats)

•Proteolipoprotein(PLP)-inducedExperimental Autoimmune Encephalomyelitis (EAE)

•Peptidoglycan-polysaccharide (PG-PS)-induced arthritis (rats)

•Adjuvant-inducedarthritis(polyarthritis or monoarthritis in rats)

•Arachidonate-inducedearedema

•Carrageenan-inducedpawedema

•Tactileallodynia(vonFreyfibers),thermal hypersensitivity (modified Hargreave’s),pawvolumemeasurements (plethysmometer)

Orthopaedic Models

•Joint/cartilage

•Bonefracture/defectrepair

•Spinalfusionandspinal instability/fixation

Custom In Vivo Methods and Models

•SerialCSFcollectionmethodology(rats)

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Molecular Imaging and RadiochemistryMolecular imaging is an established technology combining both functional and structural imaging to evaluate specific in vivo processes taking place in real time within the model of interest. The unique characteristics of molecular imaging provide investigators with an early stage solution to evaluate critical principles of new entity development, including exposure at the target site (proof of distribution), binding to the target of interest (target engagement/validation), and expression of the desired pharmacology (proof of activity).

Molecular imaging has become an indispensable tool in evaluating the biological impact of drug and chemical compounds. Through ongoing investment in equipment and expertise, along with our ability to apply them, MPI Research professionally applies imaging technology to advance knowledge that impacts all phases

of the drug development process. Our commitment to our Sponsors is to exceed their expectations and anticipate their programmatic needs for successful entity development. To that end, we have formed a partnership with our long-standing collaborators to establish the 10,000 square foot, two-story Translational Imaging Center.

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Radiochemistry and Advanced Preclinical and Clinical Imaging Research Services

•Radiolabelingofcellulartherapeutics

•Radiolabelingofantibodies,peptides,oligonucleotides, nanoparticles, and small molecules

•Tracersfortranslationalimaging– SPECT and PET for rodent

° Large molecules: 124I, 125I, 123I, 111In, 99mTc,18F

° Small molecules: 125I, 123I, 18F, 11C– PET tracers for nonhuman and

human primates

° Large molecules: 124I, 89Zr,11C, 18F

° Small molecules: 124I, 11C, 18F

•Ourcyclotronproduces11C, 13N, 18F, 124I, 89Zr

•Chemistry– Synthetic, organic, and radiochemical

expertise to label any drug or tracer

•Regulatorysupport:currentANDAs,INDs,DMFs;clinicaltrials

State-of-the-Art Data Analysis and Interpretation

MPI Research and our partners in the Translational Imaging Center provide analysis of imaging datasets in real time, allowing streamlined workflows with application-specific tools.

Key features include

•Powerfulvisualizationofcomplexdataand trends

•Variousthresholdmethodsapplied to individual, multi-modal, and dynamic datasets

•Batchprocessingwithcustomizableanalysis routines for fast, quantitative assessments

•Reliablequantificationofdistributionof radiopharmaceuticals, biologics, and small molecules in whole-body, organ, and sub-organ regions

•Multi-disciplinaryintegrationofin vitro/ex vivocharacterizationandin vivo imaging for a better understanding of distribution, kinetics, and targeting

•Kineticmodeling

•Automatedprocessesfor organ segmentation

•Availabilityofbrainatlasesforrodentsand nonhuman primates

•Dosimetrydocumentationsupport for IRB/clinical submissions

Comprehensive Services

•Smallandlargeanimal imaging modalities

•Allmajorin vivo imaging modalities– SPECT– PET– MRI– CT– DEXA– Fluoroscopy – X-ray– Laser Doppler– Ultrasonography

•Complementaryassays– Ex vivo biodistribution– Animal model development– Histology

•Quantitativeautoradiographylong- and short-lived radioisotopes – Two-dimensional, GLP-compliant– Three-dimensional

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Neurobehavioral SciencesNeurobehavioralsciencesatMPIResearchrepresentsaspecializedareaofinquirywhereinthepotentialinteractionsbetweenpharmacology and complex neurological and behavioral phenomena are explored. Such inquiries are a logical elaboration of core safety pharmacology assays, which focus on the potential deleterious effects of off-target pharmacology on key areas of the central nervous system (CNS). These kinds of studies require considerable scientific expertise, technical skill, and innovation to properly identifyandcharacterizesafetyrisks.

Exceeding expectations in the neurobehavioral sciences is a top priority atMPIResearch.Werecognizetheimportance of being fully aligned with the needs of our Sponsors. Our scientific staff is uniquely qualified in numerous areas of inquiry and is consistently able to deliver enhanced value to Sponsors through our collaborative approach. We understand the unique circumstances of every development program and apply our expertise to deliver exceptional quality data in a timely fashion.

We published the first functional observational battery for dogs and nonhuman primates (NHP) as part of the core safety pharmacology battery.

MPIResearchrecognizesthepivotalnature of studies designed to characterizeCNSsafety.That’swhywe were the first contract research organizationtovalidatefullyGLP-compliant abuse liability assays for rodents and NHPs. Likewise, our constantly developing program in auditory safety evaluation is unmatched in the industry as a model of scientific innovationandservicespecialization.We have recently added a state-of-the-art EEG data collection system that can be linked to video monitoring for the remote radiotelemetry assessment of seizureriskassessments.Ourcontinuedfocus and responsiveness provide the kind of support that our Sponsors both need and deserve toward effectively de-risking their molecules.

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Service Highlights

•Industryleadershipinabuse liability assessment

•State-of-the-artototoxicitytestinglaboratory leading the industry in GLP-compliant in-life and post-life measures of auditory function and recovery– Rodents, cats, and guinea pigs– Understanding of cochlear hair

cell restoration as current focus for consideration

– Capacity to conduct cytocochleogramsandspecializedfluorescent staining to document therapeutic efficacy of new intervention strategies

•KnowledgeableStudyDirectors,experienced in both drug control and health safety regulatory agency requirements – Expert knowledge of U.S. and

international drug control standards– Proficiency in the “8-factor” analysis

conducted independently by the FDA and DEA before NDA approval (The director of our program has a five-year employment history at the Drug Enforcement Administration)

– Clear understanding of the need to conduct neurobehavioral studies before Phase II testing with all drugs that cross the blood-brain barrier, regardless of target or therapeutic indication, particularly those entities possessing a novel mechanism of action

– Expertise with compounds, including biologics, that target known major neurotransmitter systems involved in reward/reinforcement (e.g., dopamine, opiate, serotonin, Gamma-Aminobutyric Acid [GABA]), and which may require appropriate behavioral testing

•GLP-validatedassaysfor– Self-administration (rat, NHP)– Drug discrimination (rat, NHP)– Psychomotor activity

assessment (rodent)– Dependence potential (rodent, NHP)– Conditioned place preference/

aversion (rodent)

Additional Specialized Neurobehavioral Evaluations

•Pain/analgesiaassessment– Tailflick,hotplate,Hargreave’s,

von Frey fiber, and writhing assays (rodent)

– Tail withdrawal (rodent and NHP)

Since pain assessment models should incorporate measures of general motor activity to ensure the selectivity of the new chemical entity and peripheral or CNS pain pathways, we offer

•AcceleratingRotarod Performance (rodent)

•Infra-redmotoractivitymonitoringchambers (Kinder Scientific, rodent)

•MorrisWaterMaze(mice,rats)

•Seizureinduction/blockadeassessment

•Functionalandstructural ototoxicity evaluation – Auditory Brainstem Response

(ABR) electrophysiology– Distortion product otoacoustic

emissions (DPOAE) testing– Semi-quantitative middle/inner ear

histological evaluations– Definitive cytocochleogram

preparation and analysis– Gross and microscopic middle ear

tissue examination

•Integrativeneurologicalevaluationsof objectively verifiable behavioral changes associated with movement disorders, such as – Parkinson’sdisease– Huntington’sdisease– Dystonia, ataxias, and other

paradoxical movement disorders

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Nonclinical Dose Formulation and AnalysisOptimizingdrugexposureisacrucialelementinassessingdrugsafetyandrequirescarefulchoiceofformulation.Evenwithanappropriateformulation,determiningtheappropriatedosinglevelsrequirescarefuldeliberation.Thisisnosmallconsideration; the benefit of any medication, defined by its pharmacokinetic and pharmacodynamic profile, is affected tremendously by its physical form and route of administration. Careful, precise analysis of test formulations assures proper dosing and accurate interpretation of the effect of the drug on the test system.

MPI Research embraces a philosophy of collaboration. For us, “collaboration” ismorethanabuzzword;itisthefoundation of success in contemporary drug development. We bring exceptional analytical skills to the process of understanding drug formulation and its impact on the effectiveness of promising new medications. We engage Sponsors as partners in the process, determined to exceed their expectations with high-quality results.

MPI Research helps Sponsors take that next step with confidence. We offer an extensive menu of tailored, systematic methodologies to determine the right dose formulation strategy. The pharmacokinetic and pharmacodynamics impact of formulation design requires accurate analysis and consistent, validated production of test compound formulations. We are committed to applying our expertise to assist Sponsors in method development, validation, scale-up, and manufacturing of preclinical supplies.

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Service Highlights

•DiverseanalyticalplatformsincludingWaters Alliance, Acquity and Agilent 1200 Liquid Chromatography (LC) systems with photodiode array, fluorescence, and mass spectrometric (MS and MS/MS) detection

•Variousplatformstoanalyzeproteinsand peptides including– HPLC (reversed phase, SEC,

and affinity)– Total protein assays (ultra-violet [UV]spectrophotometricandcolorimetric assays)

•Experiencewithvariousvehicletypesincluding solutions, suspensions, creams, oils, and dietary ad-mixtures

•Flexibleschedulingwithexcesscapacity to accommodate last-minute requests, changes in timelines, and rapid study starts

•Systematicapproachtomethoddevelopment and validation that results in analytical methods being available for routine analysis of formulated materials before dosing

•Start-to-finishcollaborationwithourcolleagues in drug safety, as we execute all aspects of general toxicology, safety pharmacology, and development and reproductive toxicology

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Nonclinical Ligand Binding AssaysThe human body is remarkable in its ability to wage war against a host of diseases and infections. Understanding the immune system’sarsenalprovidesvaluableknowledgethatdrivessomeofthelatestinnovationsindrugtherapy,especiallyinbiologicallyderived medicines and vaccines. An experienced, skilled partner in immunology and associated analytical services brings a powerful, competitiveadvantagetodrugdevelopers.MPIResearchunderstandsthatappropriatecharacterizationofyourbiologicandtheir associated immunomodulatory responses, along with scientific and regulatory expertise, are paramount in advancing your immunochemistry studies.

MPI Research brings exceptional expertise to immunoassay development, validation, and analysis in both knowledge and application. Our Sponsors are turning increased attention to this scientific discipline, and MPI Research is already on the cutting edge. By applying our advanced skill set today, while strategically planning for the emerging biomedical needs of tomorrow, we can increase value and better contribute to the success of our Sponsors.

MPI Research provides that “edge” with unparalleled scientific and regulatory expertise in every critical aspect of immunochemistry. With our speed, accuracy, and experience, MPI Research is the partner of choice.

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Ligand Binding Assay Capabilities

•Customizeddevelopmentandvalidation of regulated bioanalytical methods for detection and quantification of biologics using ELISA, electrochemiluminescence, and fluorescence-based methods on standard spectrophotometer, Meso Scale Discovery, Gyrolab, and Luminex platforms

•Fourtierimmunogenicityassaydevelopment and testing (screening, confirmatory, titration and NAb assays)

•Toxicokineticsandbioinformationalstatistics

•Program-levelsupportofyourbioanalytical needs from drug discovery through early development

•Fit-for-purpose(FFP)validation of commercial and custom-built single or multiplexed biomarker immunoassays (Luminex, Meso Scale Discovery, GyroLab)

•RapidturnaroundonFFP quantitative and immunogenicity assay development and analysis to support candidate selection and your drug discovery needs

•Experiencewithassessingsystemicexposure of a variety of antibody drug conjugates– Kidney damage biomarkers

(TIMP 1 and NGAL)– Alzheimer’sdiseasebiomarkers

(Tau and Aβ42)

•Extensiveexperiencewithmonoclonalantibody analysis, including common biosimilars (Rituxan, Herceptin, Enbrel, Neulasta)

•Experiencewithassessingsystemicexposure of a variety of antibody drug conjugates

•FullyintegratedLIMStotracksample,drug, equipment, and material storage and maintenance

•WasonLIMSforrapiddataanalysis and reporting

Ligand Binding Assay Platforms

•GyroLabworkstations

•MSDSectorImagers

•ELISAplatereaders

•Bioplex200s(Luminex)

•PerkinElmerEnvision(AlphaLISA™)

•PerkinElmerJanusautomated liquid handlers

•TomtecQuadraautomated liquid handlers

•BioTekmicroplatewashers

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Safety PharmacologyDeveloping a predictive understanding of a medication safety profile is more important than ever. As part of this endeavor, modern safetypharmacologystudiesmustbedesignedtopreciselycharacterizepotentialfunctionalliabilities,ideallydeterminingdose-responserelationships including onset, peak response, mechanism(s) of action, and/or potential reversibility. Translating data from key preclinical safety pharmacology studies to human clinical trials and beyond represents a complex enterprise that must be expertly conducted to ensure progression of therapeutic, palatable, and safe drug candidates.

Raising the bar on the performance of safety pharmacology is another way MPI Research continues to advance its commitment to serving Sponsors. Accurate, meaningful, and timely study results that clearly demonstrate the functional safety profile of a drug candidate are essential. As partners with our Sponsors, we are focused on delivering high-quality, timely, and relevant data that facilitate development decisions. Effective collaboration is a powerful contribution to the success of our Sponsors as we assist them in moving their compound to the next phase.

The safety pharmacologists of MPI Research continually strive to adopt and develop the emerging technologies and essential skills that will drive enhanced insight. We facilitate overall program development by employing study designs appropriate to defining pharmacology, with consideration to the individual circumstances of each drug candidate. Our professional approach is collaborative and individualized,likewisefocusingon the unique needs of each Sponsor.

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Services Highlights

•Conformancewithinternationalregulations and guidelines

•Theexperience,insight,andflexibilityrequired for the development of customizedmodelstoappropriatelycharacterizeawiderangeoftherapeutic targets

•Recenttechnologicadvancesallowus to offer our clients the flexibility necessary to ensure the highest quality data while providing the best possible animal care

Cardiovascular System

•Remotetelemetrymonitoringinfreelymoving large and small animals with calibrated continuous data collection, using appropriate analytical methods for quantitative and qualitative data

•Fullyvalidated,non-invasiveremotetelemetry monitoring system for large animals provides an alternative to surgical instrumentation

•hERGassessmentviawholecell patch clamp

•Restrained/anesthetizedmodels

•Cardiacoutput/arterialflow

•Vascular/peripheralresistance

•Ventricularpressure,pulmonary arterial pressure

•Ultrasound/echocardiography

Respiratory System

•Whole-body,head-out,and dual-chamber plethysmography in small animals

•Remote,calibratedtelemetrymonitoring in freely moving large animals with continuous respiratory data collection

•Rate,volume,andsupplementalderived respiratory mechanics parameters

•Bloodgasanalysis

•Lungresistanceandcompliancemeasuresinanesthetizedrodents

Central Nervous System

•FunctionalObservationalBattery(FOB)for small and large animals

•Quantitativelocomotorevaluations

•Higherorderneurofunctionalendpoints

•CNSelectrophysiology (EEG-based sensory, motor, andgeneralizedassessments, including quantitative methods)

Renal System

•Urinaryscreeningand definitive functional evaluations in multiple species

Gastrointestinal System

•Gastricemptyinginrodents

•Gastrointestinaltransit in multiple species

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Small Molecule Clinical Bioanalytical AnalysisThere was a time when bioanalytical services were relatively simple, but that time has passed. MPI Research has moved from nonspecificassaystothecurrentdisciplinethatpreciselyanalyzessmallmolecules,biopharmaceuticals,andtheirmetabolites. Drugdevelopmenthascometodependuponscientists’abilitiestoquantifythesesubstancesinbiologicalsamplesbyusing cutting-edge technology and processes.

Making connections is the heart of the scientific process—testing a hypothesis, analyzingresults,andtakingthenext step. MPI Research makes those connections in the laboratory and with our Sponsors. The answers we seek are of critical importance. In the realm of clinical bioanalytical analysis, we link our expertise across a spectrum of disciplines to deliver results that drive decisions and fuel the next stage in drug development.

MPI Research brings together a wealth of experience in bioanalytical analysis of small molecules, oligonucleotides, peptides, and protein therapeutics. A wide range of technological tools are employed—including a proprietary electronic laboratory notebook (eLN)—with superior analytical services and high-throughput examination to deliver results quickly and precisely.

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Service Highlights

•Regulatedbioanalysisusing liquid chromatography tandem mass spectrometry

•Significantredundancyinliquidchromatography mass spectrometry (LC-MS/MS)(API5000)systemsequipped with high performance liquid chromatography (HPLC) and ultra-high performance liquid chromatography (UHPLC) capabilities

•Gaschromatographytandemmassspectrometry for smaller molecular weight(<150amu),orvolatilecompounds such as fatty acid methyl esters (DHA/EPA) or even neurotransmitters

•Comprehensivebioanalyticalandpharmacokinetic services for first- in-human trials

•Bioequivalencestudiesincludingexpedited analysis for first-to-file opportunities with timelines for clinical summary reports in as few as 20 days from drug availability

•High-throughputanalysisusingstate-of-the-art automation and a proprietary eLN with advanced data management and publishing capabilities

•Routinetimelineforsampleanalysis of five-day turnaround for QC data

•Standardtimelinesformethoddevelopment and validation of a new chemical entity of two weeks for small molecules

Our current resources include

•ABSciexAPI5000MS/MSsystemsequipped with high performance liquid chromatography (HPLC) and ultra-high performance liquid chromatography (UHPLC) capabilities

•WatersSynaptG2highresolution time-of-flight mass spectrometer

•Ultra-violet(UV)andfluorescencedetection HPLC systems

•TomtecandPerkinElmerliquidhandling systems for automated sample preparation

•TissuesamplepreparationusingCovaris adaptive focused acoustics (AFA) ultrasonic extraction instruments, equippedwithcryogenicpulverizationof hard tissues

•CentralizedThermoWatsonLIMS™ for data management and reporting

•Centralsecurityalarmmonitoringsystem with 24-hour, card-controlled facility access

•On-siteemergencypowerbackup forallsamplestoragefreezers (-20°C, -70°C)

•Freezertemperaturemonitoringwithremote notification capability

•ACpowerfailuremonitoringsystemswith immediate notification capability

•Incrementalnightlydatabackupsandfull weekly and monthly backups

•Backupgeneratorsanduninterruptiblepower supplies

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Small Molecule Preclinical Bioanalytical AnalysisWhen it comes to bioanalytical services, one-stop shopping is more than convenient. It is vital to the integrity of the process and to the value of the results—that is, as long as your partner has integrated the right scientific expertise across its operations. This is especially important at the preclinical level in drug development, where go/no-go decisions need to be made early and confidently. A misstep here means lost time and resources. MPI Research offers unrivaled bioanalytical services, fully integrated with our on-site preclinical research laboratories that expedite results and facilitate collaboration. From method development through sample analysis and reporting, we maintain high-quality standards in a responsive working environment.

Asacontractresearchorganization, MPI Research offers immense experience and valuable contributions to our Sponsors. In preclinical bioanalytical analysis, we provide a rich, comprehensive perspective that our Sponsors rely on to accelerate moving their compounds along the drug development pathway.

MPI Research brings superior bioanalytical services to the preclinical realms that are fully intertwined with their discovery and clinical capabilities. Our researchers understand the magnitude of investment required to develop new medicines, so they work hand-in-glove with Sponsors to design effective studies, streamline analysis, employ the latest technology, and deliver accurate data rapidly. We provide quality services that allow our Sponsors to advance new treatments, bringing hope to patients worldwide.

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Service Highlights

•Targetedmethoddevelopmentforsmall molecules, oligonucleotides, peptides, and protein therapeutics by experienced senior scientists

•Structured,systematicapproachthatincorporates orthogonal assay designs when appropriate

•Expertiseinbioanalysisacrossawidevariety of standard and unconventional biomatrices (e.g., ocular, toenail, and muscle)

•Bioanalysisbyliquidchromatographytandem mass spectrometry of protein therapeutics using signature peptides in a bottom-up approach

•Comprehensivepharmacokinetic (PK)/toxicokinetic (TK) analysis services fromleadoptimizationtoclinicalproof-of-concept

•Methodvalidationthatconforms toregulatoryandindividualizedSponsor requirements

•Broadlicensingforradio-nuclearandcontrolled substances

•Proprietaryelectroniclabnotebooksystem for streamlined sample handling, reliable chain-of custody, and efficient reporting

•ThermoWatsonlaboratoryinformationmanagement system

MPI Research uses the most advanced instrumentation and technology available

•Liquidchromatographymassspectrometry (LC-MS/MS) (API5000)systemsequipped with high performance liquid chromatography (HPLC) and ultra-high performance liquid chromatography (UHPLC) capabilities

•WatersSynaptG2highresolution time-of-flight mass spectrometer equippedwithnanosprayionization

•Gaschromatographytandemmassspectrometry (GC-MS/MS)

•HPLCwithultra-violet(UV),fluorescence detection (FLD), and diode array detection (DAD)

Our capabilities also include

•Roboticautomationforhigh-throughput sample preparation

•24/7samplereceiptmanagement

•Extensivestoragecapabilities at -20°C and -80°C

•Backupgeneratorsand uninterruptable power supplies

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Surgical Efficacy and Medical Device EvaluationEnsuring the safety of a drug candidate or medical device is critically important. A developer also needs to know if the product being tested does what it is intended to do and how well it performs. Therefore, it is essential that life science companies can count on an experienced, knowledgeable scientific team.

By placing your medical device or combination product study at MPI Research, you can rely on the most advanced methods, effective evaluations, comprehensive verifications, and accurate validation of your medical device designs.

Like our Sponsors, MPI Research recognizestheincredible advancements and equally superior diagnostic potential that medical devices and combination products provide to healthcare in our society. Our dedicated scientific team works closely with Sponsors to deliver accurate results quickly, consistently, and cost-effectively.

MPI Research provides decades of experience and collaborates with Sponsorstodevelopcustomizedstudiesusing advanced techniques that best meet their needs. Our industry-leading surgical facilities and highly trained staff are all available at one location to provide Sponsors with advanced research capabilities in a wide range of species.

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Services Highlights

•DedicatedStudyDirectors

•Experiencedtechnicalsurgeons– Certified by the Academy

of Surgical Research

•Fullstaffofsurgicaland in-life technicians

•On-siteclinical/surgical veterinarians(DVMs)

•On-siteanatomicand clinical pathologists

•Dedicatednecropsystaff

•ConsultingMDsandsurgicalDVMs

•Threededicatedlargeanimal surgical suites

•Onededicatedsmallanimal surgical suite


State-of-the-Art-Equipment

•Fluoroscopes

•Ultrasounds

•X-ray/faxitron

•ScancomicroCT

•MobileMRI(Siemens1.5TMagnet)

•MobileClinicalCTUnits(32or64slice)

•Intravascularultrasound

•Micro-PETandSPECTscanners

Surgical Facilities



Medical Device Models

•Cardiacandperipheralmodels for cardiovascular

•Orthopaedicmodels

•CentralNervousSystem(CNS)andperipheral models for neurological

•Dental,gastroenterological,drugdelivery, urologic, and wound healing

Surgical Capabilities and Models

•Orthopaedicmodels– Joint/cartilage – Bone fracture/defect repair – Spinal fusion and spinal

instability/fixation

•Renalmodels– Aminoglycoside nephrotoxicity– Renal ischemia-reperfusion injury– Streptozotocin-induceddiabetic

nephropathy– Glomular filtration rate and renal

blood flow evaluations– Renal transplantation– Goldblatt hypertension – Partial nephrectomy for

evaluating hemostasis

•Neurologicalcapabilities– Spinal cord contusion – Intrathecal device implantation– Epidural device implantation– Intracranial device implantation– Stereotaxic administration

•Woundhealingmodels– Full thickness excision – Split thickness wound created

with dermatome– Full thickness incision

•Cardiovascularmodels– Acute myocardial infarction– Congestive heart failure– Chronic cardiac and

peripheral ischemia– Peripheral arterial disease

Stem Cell Surgical Therapies and Study Designs

•Therapies– Autologous cell therapy– Allogeneic cell therapy– Embryonic cell therapy

•Studydesigns– Proof-of-concept– Safety and biodistribution– Tumorigenicity– Allogeneic cell types

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Targeted DeliveryScientists know that most drugs are not targeted to the specific site of the disease in the body. The majority of drugs are delivered throughoutthebody,whichcangreatlyreducethedrug’sefficacy.Targeteddrugdeliveryoffersseveral,preferredadvantages,includingdecreased dosage frequency, a more constant effect of the drug, and fewer, potential systemic side effects.

MPIResearchhastheknowledgeandexpertisetodeliveryourdrugtoprolong,localize,andtargetthecorrectorgansandtissueswithout creating systemic complications. Our highly trained staff is available to explore how we can assist Sponsors and deliver drugs with improved efficacy.

Targeted delivery of drug therapies provides greater expectations for improved/positive medical outcomes. Exceeding those expectations is the vision of our Sponsors—a vision MPI Research shares. Our highly experienced team applies the latest technologies and insights to assist our Sponsors in their work with our cutting-edge,high-quality,andcustomizedstudy protocols. Just as our Sponsors target diseases in unique ways, we target our work to help them succeed.

MPI Research has the expertise to lead the charge and collaborate with Sponsorstodevelopcustomized studies, assuring candidates are moving along the drug development pathway accurately and quickly. Our robust study designs, state-of-the-art surgical facilities, wide selection of animal models, and comprehensive array of delivery routes assure an ideal environment for targeted delivery evaluation.

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Service Highlights

•DedicatedStudyDirectorswithmorethan 70 years of combined experience

•Experiencedtechnicalsurgeons– Certified by the Academy

of Surgical Research– More than 60 years of

combined experience

•Fullstaffofsurgicaland in-life technicians

•On-siteclinical/surgical veterinarians(DVMs)

•On-siteanatomicand clinical pathologists


•ConsultingMDsandsurgicalDVMs



Delivery Routes

Targeted test-article delivery routes available include but are not limited to

•Directintestinal

•Intrahepatic

•Portalvein

•Intramyocardial

•Intra-aortic

•Intraventricular

•Intra-articular

•Arterial/venous

•Intravesicular(bladder)

•Intrathecal/epidural

•Organ-specific

•Intracranial

•Intraprostatic

•Bileductcannulation

•Subretinal

•Intravitreal

•Intraspinal

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MPI ResearchCorporate Headquarters54943NorthMainStreetMattawan, MI 49071 USA

Tel: +1.269.668.3336Fax: [email protected]

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Complete Target-to-Clinic Capabilities€¢pls...immune disorders, rare orphan diseases, and ophthalmology Animal Welfare Be sure to ask us about our comprehensive animal welfare program,