Company Introduction

THE FRONTAGE ADVANTAGEAttention, Efficiency, and Expertise

Who is Frontage Laboratories?

• We are an early phase drug development company

• Started in 2002

• Currently 225 people

• We have grown organically and through acquisition (clinical)

• selected as one of the fastest growing companies in the

Philadelphia region – 4 years in a row

• Facilities in US and China

Working with Frontage:Advantage #1 – Expediting your

development program

ACCOMPLISH MORE WITH ONE SERVICE SUPPLIER

Frontage has all that you need to move your compound from preclinical development through Phase I – II clinical studies and beyond

• API synthesis • Preclinical / ADME Services• Dosage form development • GMP manufacturing • Clinical study execution via 72-bed CRU• Bioanalysis & Biomarker / Immunology• Regulatory filing and support

Working with Frontage:Advantage #2 - 100% Attention

WHAT SETS FRONTAGE APART??

Every project is on the front burner – 100% attention

Communications are easy to manage, coordinated, and routinely scheduled

Our project management leaders each have a minimum 15 years experience in the industry – You receive the best project leadership possible

Cross functional project teams allow for smoother working process and less administration

WE WORK HARD TO MAKE SURE YOUR COMPOUND IS FRONT AND CENTER !!!

Working with Frontage:Advantage #3 – Top Scientific Team

YOUR DRUG DEVELOPMENT PROGRAM REQUIRES THE BEST TALENT

Frontage has a significant number of advanced-degree scientists – >60% of our team

Extensive personal experiences in all phases of drug development – from discovery to clinical, from laboratory to commercial launch

Involved in numerous preclinical, first-in-man, late stage clinical, generic and OTC development projects

QUALITYGlobally managed, centralized data (all sites WATSON LIMS)Globally managed Quality System

SCIENCEFrontage has the best training system in the industry

• Management team has international experience• Scientists receive international training, working hands-on at US

facilitiesUniform testing platforms and ability to pool resources to ensure best scientific coverage Established method transfer procedures

LOGISTICSContinuity of Service is guaranteed by Frontage – if there are any potential shipment issues to China, US laboratory will serve as back-up facility

Working with Frontage: Advantage #4 – Frontage US –China Operation

FRONTAGE - BACKGROUNDService Offerings

Our Locations

Hackensack, NJ (NYC area) Phase I-II Clinical Operations(72 beds) – expanding to 160 beds in 2010

Princeton, NJ CRO support services

Malvern, PA (near Philadelphia)

Bioanalytical and Bioassay services, ADME servicesGMP API manufacturing

Exton, PA(near Philadelphia)

Corporate HeadquartersPharmaceutical Analysis, Formulation Development and GMP CTM Manufacturing

Shanghai, China Bioanalytical and Bioassay services, Pharmaceutical Analysis and Formulations Development

Zhengzhou, China Phase I Clinical Operations (130 Beds)

Beijing, China Clinical Services and Regulatory Affairs,Future home of Formulation Development Beijing Pharmaceuticals Manufacturing Site

Alliances with GLP Preclinical Centers in the US, Shanghai & Suzhou, China

Preclinical Research centers – rodents, canines and non-human primates

More than 200 clients around the world: US, EU, JP, China

Global top 10, mid-size and virtual pharmaceutical and biotech firms

Chinese generic and innovative drug companies

Frontage has had successful FDA inspections (10+) and numerous client inspections and audits for both our US and China facilities

Our Clients

DMPK Preclinical ServicesOverview

WORLD-RENOWNED LEADERSHIPAccomplished team of professionals Thought leaders in drug metabolism - over 100 years of collective experience in DMPK and ADME support and published research

DMPK SERVICESSupport for discovery pharmacokinetic studiesDiscovery-stage in-vitro studies metabolism evaluationsDiscovery-stage ADME studiesDrug development stage DMPK support and metabolic evaluations

EFFICIENT SYSTEMSTechnical leadership allows for quick completion of studiesPrice leadershipCapabilities in US and China

Discovery DMPK Services:PK Studies

n PK in Non-Rodent

n Target Tissue Exposure(Total and Free)

n High-dose Pharmacology Support

n Salt Selection

n Linearity Assessment

n Renal/Biliary Clearance(As Needed)

n Ascending Dose PK Rodent andNon-Rodent

n TK and Formulation Support

n Additional Species PK

n Food Effect

n Interspecies Scaling

ExploratoryExploratory DiscoveryDiscovery Pre-SelectionPre-Selection Lead CandidatesLead Candidates

n PK/PD Biomarker Assessment

n PK in Other Species including Rodents and Non-Rodents(As Needed)

In-Life and Non-GLP Bioanalytical

DTDT

PK in Pharmacology Model(s)

Help with POC, MED exposure

Discovery DMPK Services:In-Vitro DMPK Studies

• Intrinsic Clearance• CYP IC50/MBI

ExploratoryExploratory DiscoveryDiscovery Pre-SelectionPre-Selection Lead candidatesLead candidates

• Metabolite Profiling/ Structure Elucidation - metabolic soft spots - structure optimization• Metabolic Stability

(microsomes / hepatocytes)

• Plasma Profiling/ - pharmacology species - PK and tox species (rodents, dogs, monkeys)

• Cross-species metabolism (microsomes/hepatocytes)• Identification/isolation of major human metabolites

• Metabolism in human plateable hepatocytes• Metabolic pathways elucidated

• Caco-2/MDCK permeability

DTDT

n Plasma/Microsomal Protein Binding

n Blood/Plasma ratio

n CYP Reaction Phenotyping

n P-gp Transport/ Inhibition

n CYP Induction(PXR/Human Hepatocyte)

Drug Development Phase DMPK:Metabolite Studies

14

Phase 2 toPhase 2 to Post-NDAPost-NDAPOC NDAPOC NDA

Phase 0Phase 0 INDIND

Phase 1Phase 1SAD & MADSAD & MAD

n In vitro metabolism - [14C] compound

n Single dose 14C metabolism and mass balance (rodent andnon-rodent)

n Multiple dose metabolite profiles from IND enabling studies

n Enzyme induction(ex vivo), if needed

n Mechanistic studies to support safety assessment(as needed)

n Metabolite profiles from SAD/MAD studies

n Determination of exposure of major human metabolites in tox species

n DDI support and kinetic assessment of metabolite formation [14C] in vitro

n Tissue distribution, brain penetration/target tissue uptake

n 3H mass balance and tissue distribution

n Human [14C] ADME study

n Metabolism support of clinical studies (DDI, pediatric, elderly, hepatic/renal, QTc, etc.)

n Placental transfer, milk excretion

Discovery ADME Studies

Metabolic stability (2 time points) – microsomes / hepatocytes

Intrinsic clearance – microsomes / hepatocytes

In-vitro metabolite identification for structural optimization

Cross-species metabolite profiles across species – microsomes / hepatocytes

CYP-450 inhibition – LC/MS/MS based assays (available May 2010)

CYP reaction phenotyping – cDNA

Plasma protein binding

Discovery ADME Studies

Plasma metabolite profiling

Plasma/blood partitioning studies

Isolation and characterization of metabolites

In-Life PK studies (in-life conduct through partners – internal small mammal capabilities available June 2010)

CACO-2 / MDCK permeability studies (available July 2010)

Quantitative LC/MS analysis (non-GLP) from PK studies

Development DMPK Studies

Reaction phenotyping (cDNA & chemical inhibition)

Metabolite profiling and identification – Tox/FIH studies

Isolation and characterization of metabolites

Delineation of metabolic pathways

CYP inhibition studies. Definitive IC50 & k1 determinations (April 2010)

CYP induction in livers of rodents, canines & primates (June 2010)

Development ADME Studies

Synthesis of metabolites and stable-labeled materials

The Frontage team has specific expertise for development of Metabolites In Safety Testing (MIST) packages.

Identification of metabolitesQuantitation of metabolitesAUC determinations (using non-radiolabeled compounds)

Mass balance studies in rodents – 14C and 3H and tissue distribution studies will come on line second half of this year

DMPK Leadership Team

• Abdul Mutlib: Twenty years of experience in pharmaceutical industry, (PhD) DuPont-Merck, Pfizer, Hoechst-Roussel (Aventis), Wyeth Five years post-doc in academia, 60+ publications, patents Editoral Board: Chemical Research in Toxicology

• Jack Wang:• Jim Burleigh: Experienced technical supervisor with over 25 years of experience (BS) in conducting ADME studies in laboratory animals

• Peter Liu: Experience in developing, validating and implementing complex (MS) LC/MS/MS assays for the quantitation of drugs in biological

matrices in a GLP, GLP-like and non-GLP environments. Twenty years experience in bioanalysis.

DMPK Leadership Team

Team Member Background Description

Abdul Mutlieb (PhD) Twenty years of experience in pharmaceutical industry, DuPont-Merck, Pfizer, Hoechst-Roussel (Aventis), WyethFive years post-doc in academia, 60+ publications, patents, Editoral Board: Chemical Research in Toxicology

Jack Wang (PhD) More than 20 years of experience in mass spectrometry, structure elucidation, drug metabolism and analytical chemistry. 30+ publications, patents, book chapter.

Jim Burleigh (BS) •Experienced technical supervisor with over 25 years of experience in conducting ADME studies in laboratory animals

Peter Liu (MS) •Experience in developing, validating and implementing complex LC/MS/MS assays for the quantitation of drugs in biological matrices in a GLP, GLP-like and non-GLP environments. Twenty years experience in bioanalysis.

DMPK Leadership Team continued:

Team Member Background Description

Li Shen (PhD) More than 10 years of experience in Development Drug Metabolism. Experience in mass balance studies, metabolite profiling, enzyme ID and kinetics, drug-drug interaction, enyme induction and inhibition. Expert in DM studies to support projects from pre-IND through post-registration.

Seonghee Park (PhD) Experience in Caco-2/MDCK permeability assays, other transporter assays, sandwich-cultured hepatocytes, protein binding & in vitro metabolism.

Bioanalytical Services

INDUSTRY - LEADING TECHNICAL CAPABILITIESHighest ratio of advanced degreed scientists working on the benchFrom data management and sample handling to analysis platforms, Frontage has invested in state-of-art technology, including global Watson LIMS systemStreamlined method development - typically completed within 1 weekAnalyte stabilization techniques help Frontage to overcome tough technical challenges – prevents degradation of analytesOne of the largest laboratories on the East Coast, USA and China

EFFICIENT PROJECT MANAGEMENTGlobal study supportOver 35,000 samples analyzed per month in US and China

Bioanalytical Services

LC / MS / MS

Bioanalytical Services

GC & LC/MS/MS METHOD DEVELOPMENT & VALIDATIONDemonstrated success in developing methods for compounds requiring high sensitivity measurements (picogram / mL)Small and large molecule analysisOne of the most proficient labs in US and China – tackling technically challenging projects globally

IMMUNOASSAY DEVELOPMENT & VALIDATIONMSD Electrochemiluminescence PlatformELISAAntibody and platform development

BIOMARKER ASSAY DEVELOPMENT & VALIDATION

17 LC/MS/MS systems in USA (10 API 4000, 3 API 5000, 3 4000 API Q-trap, API365),

6 LC/MS/MS in China (4 API 4000, 1 API 5000, 1 API 4000 Q-trap)

More than 30 HPLC systems

3 MSD Electro-chemilluminescence Instruments

Watson LIMS system – centralized data for US and China

Tomtec and Tecan Liquid handling systems

Ultrasonic Tissue Processing Equipment

Emergency Power Back up

Monitoring system for storage freezers

State-of-Art Equipment and Processes

High Throughput Sample Preparation

State-of-Art Equipment and Processes

Electrochemiluminescence – Large Molecule Analysis

State-of-Art Equipment and Processes

Covaris Ultrasonic Extractor – Tissue Processing

State-of-Art Equipment and Processes

Exton CMC Facilities

• Analytical Labs– 8,000 Sq Fto GMP Analytical Instrumentationo ICH Stability Storage

• Formulation Development & GMP Area ( 10,000 Sq Ft)o Solids R&Do Liquids / Creams / Ointments R&D o Potent Compounds suite (GMP)o Solids Dosage Manufacturing (GMP)o Liquids / Creams / Ointments (GMP)o Sterile Compounding (GMP)

CMC Services - Analytical

GMP & GLP ANALYTICAL SERVICESMethod Development, Validations and Transfers

• HPLC (25 systems), UPLC, GC, LC/MS/MS, GC/MS

ICH Stability Evaluations – over 4,500 cubic feet of storage• Standard and Custom Conditions

Dissolution Testing • Comparator Study Capability with On-line HPLC & UV

Unknown Impurity Identifications• Fraction Collection, Purification, Synthesis, ID by MS & NMR

Finished Product Release Testing & Customer Complaint Investigations – CTM and Commercial ProductsParticle Size Analysis and Wet Chemistry

Analytical Equipment

Analytical Equipment

• 25 HPLC Systems – UV/PDA, CAD, Refractive Index, Fluorescenceo Three vendor platforms for ease of method transfer / robustness

(Waters, Agilent, Shimadzu)

• UPLC Systems – PDA and MS

• 3 GC Systems – FID with Headspace

• Ion Chromatography (Dionex)

• LC/MS/MS and GC/MS - Impurity ID

• 10 Dissolution Systemswith on-line HPLC and UV analysis

• Particle Size Analysis & Wet Chemistry (KF, Titrations)

CMC Services - Stability

CMC Services - Stability

• Stability Chambers Are Fully Compliant With ICH Guidelines

• 7 Walk-in Stability Chambers And 5 Reach-ins With Over 4,500 Total Cubic Feet

• Smaller Chambers And Photo stability Chamber For Special Studies

• Lab Watch Monitoring System

• Emergency Back-up Power Generator for continuous operation

CMC Services - Formulations

FORMULATION DEVELOPMENTRational Development Processes (CTD / QBR formats)Pre-formulation characterization and screening

• Physicochemical evaluations• Excipient compatibility

Immediate and Controlled Release Development Expertise• Oral Solid Dosage Forms – Immediate and Controlled delivery

systems• Sterile – Parenteral, Lyophilized, & Ophthalmic Forms• Creams, Ointments and Gels• Nasal Sprays (including characterization – droplet size,

geometry• High Potency Suites

Proof of Concept Studies in Animals via China facilitiesProcess Optimization and Improvements

Clinical Manufacturing Clinical Manufacturing

• Phase I –II Scale

• Full Range of Capabilities

o Oral Solids -High Shear, Encapsulation, Compression,Tablet Coating, Fluid Bed

o Sterile manufacturing utilizing disposable bag system

o Semi Solids

o Liquids capabilities to 100 L

o High Potency Suites

CMC Services

GMP CONTRACT MANUFACTURING – CLINICAL TRIAL MATERIALS

Oral Solid Dosage Forms• API filling in Capsules – Accurate Dosing System• Standard Tablet and Capsule filling• Tablet in Tablet technology (Tri-layer Tablet Press)• Liquid – filled Capsules• Enteric Coating

Sterile Dosage Forms• Aseptically-filled vials using disposable mixing and filling technology• Nasal Sprays• Suspensions

Topical Dosage Forms• Creams, Ointments, Gels

API’s via chemical synthesis

CMC Services

API SYNTHESIS AND RESEARCH CHEMISTRY

GMP Synthesis of Small Molecules – up to 5 kg scale

Reference Standard Synthesis– Metabolite Synthesis & Cold Labeling– Impurity Identification and Purification Projects– Process Development & Optimization– Sourcing & Scale-up to Commercial

Collaborations

• BEIJING PHARMACEUTICALS GROUP– Large Scale, FDA-inspected GMP manufacturing

• PIERRE FABRE (FRANCE)– Patented Nanotechnologies for enhancing bioavailability of low

permeability / low solubility drugs– Taste masking of bitter API’s

• HERAEUS (GERMANY)– Cytotoxic API Manufacturing via chemical synthesis and fermentation

• SINCLAIR RESEARCH (MISSOURI) & CALVERT LABORATORIES (PA)– GLP Preclinical research centers

• PRECLINICAL RESEARCH CENTERS IN CHINA– Frontage - supervised studies for non-GLP evaluations

Biomarkers & Biologics

Biomarker and Biologics

Immunoanalytical Testing (Ligand-Binding Assays)

Specialized Assays & Services

Biologics:Assays & Services

Biologics: Assays & Services

CELL-BASED ASSAYS (PRE-CLINICAL AND CLINICAL)

• Potency assay • Cytotoxicity and Proliferation assays• Immune function assays• Flowmetric assays• Tissue processing/staining for IHC• Custom assay development for client needs

USA AND CHINA• Frontage provides these services at both facilities• Possible expansion to other countries

US Clinical Research Center: Background

• Founded in 1994 – 16 year track record of service excellence

• 72-bed unit located in Hackensack, New Jersey• On-site, full-time principal investigator with 20 years of

emergency medicine experience• Phase 1 and 2a studies• On-site pharmacy (temperature controlled, limited

access) for study drug storage, packaging / labeling and retention

• Extensive subject database (healthy volunteers / special populations) and dedicated recruiting staff

• Local clinical laboratory with 24-hour turn-around• Central IRB (rapid review process)

Clinical Research Centers:Phase 1 and 2 Studies

• PHASE 1 AND 2A STUDY EXPERIENCE First-in-human Pharmacokinetics Single dose escalation / repeated dose Absolute and relative bioavailability Bioequivalence studies (pilot, pivotal, fed, fasted) Drug-drug interaction (DDI), drug-alcohol and drug-food

interaction studies Oral, injectable, inhaled, intranasal NCEs, peptides, hormones Thorough QT (TQT) study evaluations PD assessments / Biomarkers Safety and tolerability

assessments

Clinical Research Centers:Subject Recruitment

• Proactive recruitment planning & execution• Extensive volunteer database (5000+ subjects)• Wide-ranging media options – newspapers and local

publications, employment guides, local flyers and postings, radio

• Local networking – schools, businesses, health fairs• Dedicated recruiting staff

Clinical Research Centers:Proof-of Concept Studies

– Proof of concept studies• Cardiovascular – endothelial dysfunction, HTN, early CV disease

(Endo-PAT vascular compliance devices)• Metabolic – Type 1 and 2 DM, obesity, metabolic syndrome,

dyslipidemias (dietician, on-site Hologic Dexascanner)• Gastroenterology – sigmoidoscopies, colonoscopies,

gastroesophageal reflux, irritable bowel syndrome, diarrhea • Women’s health – pre- and postmenopausal women, osteoporosis,

hormone replacement, sexual dysfunction• Men’s health – testosterone replacement, osteoporosis, sexual

dysfunction• Dermatologic – acne, actinic keratosis, psoriasis• Inflammation – osteoarthritis, rheumatoid arthritis• Ophthalmologic assessments• Cognitive assessments• Excellent access to specialty physicians as needed

Clinical Research Centers:Study Time Lines

• Rapid IRB submission process (Central IRB)– Study-specific approval typically within 8 business days of

submission– Able to begin screening immediately with IRB-approved generic ICF

• Dosing within 3 weeks

of contract execution

• Same-day shipment of plasma

samples from CRC to

Frontage BioA laboratory

• Prompt (within 48 h) report of preliminary PK/BE results

Clinical Research Centers:Study Metrics

Since 2006, we have performed:

• Over 25 bioequivalence studies (pilot and pivotal)– 2-way and 3-way cross-over– Fed and Fasted– Over 700 healthy male/female volunteers enrolled– Enrollment rate >98%– Completion rate >90%

• Over 25 Phase 1 studies– Over 1000 healthy male/female volunteers and special populations

enrolled

– First-in-human, single and multiple dose, bioavailabilty, formulation, DDI, PK, safety/tolerability

– Enrollment rate >98%– Completion rate >93%

• New US clinic to be constructed• 160-bed state-of-the-art Phase 1 clinic• Northern New Jersey location• Access to public transportation and diverse subject population• Ability to run 3 separate 24/36 subject panels simultaneously• Separate area with hospital beds • Operational 24 hours per day / 7 days per week• On-site pharmacy (storage/preparation/retention)• Flexible site use / expanded recreation & dining areas• Expected to be operational Q2/Q3 2010

• 2009: 120-bed clinic became operational in Zhengzhou, China

Clinical Services Moving Forward

• Full-service CRO for Phase 1-3 studies• Headquarters in Princeton, NJ• Experienced Senior Management Team• Protocol Design, ICF and CRF Development• Project Management• Clinical Data Management (Oracle Clinical)• SAS Programming • Biostatistical & Pharmacokinetic (WinNonlin) Analysis• Medical Writing• Regulatory Support / Submissions

CRO Support Services

• Dedicated 130 bed unit located in Zhengzhou, China

• Fit-Out completed in Q2 2009

• Supported by the First Affiliated Hospital of Zhengzhou University (4,000 bed hospital)

• ICH GCP compliance

• SOPs strictly follow Frontage’s U.S. practices

China Clinical Research Center

Clinical Pharmacology & Regulatory Affairs

• CLINICAL PHARMACOLOGY CONSULTATION

• CONSULTATION ON DRUG DEVELOPMENT & REGISTRATIONS

– Clinical Pharmacology– CMC– Toxicology– Regulatory Project Management

• REGULATORY FILINGS (IND, NDA, & ANDA)

• FDA COMMUNICATIONS– Agent representation– FDA Meeting Management– Liaison Activities

Get the Attention You Deserve

• OUR ORGANIZATION HAS BEEN BUILT WITH YOU IN MIND!– Project management and program managers have proven

industry experience– Key leaders of each business unit have proven track

records in the industry– We are sufficiently staffed in each area to manage

individual service projects or integrated programs– Proven Quality – strong compliance and technical record

in the industry

DISCUSSION & NEXT STEPS