VP, Bioanalytical Operations October 13, 2011 Agenda Platform - PowerPoint PPT Presentation

Afshin Safavi, Ph.D. VP, Bioanalytical Operations October 13, 2011

Agenda Platform BioAgilytix vs. Instrument Preclinical- Current Clinical vs. Immunoassay Manufacturing Platforms Assay Needs

Introducing BioAgilytix Labs

Company Overview  Founded in 2008  Located in RTP, NC  CRO focusing on Ligand- Binding and Immunoassay

Preferred Provider & Employer • Top 5 Pharmaceutical Trusted • Top 10 Biotech Partner • Top 5 Agriculture Recognized Nominee- Life Sciences Company of the Year- 2010 #7 in the Triangle Area; #74 in the South - 2011 Business Winner 2011 Finalist 2010 Award Winning Employer A Business Partner with Proven Sustainability

Our Focused Service Offerings Immunoassays Multiplexing PK Immunogenicity Cell-based Assays PD Biomarkers Non-GLP, Spirit-of-GLP, GLP & GMP

Supporting Various Stages of Drug Development Post Discovery Preclinical Clinical Marketing

Supporting Various Stages of Drug Manufacturing Process Small Scale Large Scale Pre-Clinical Material Manufacturing Clinical Material Manufacturing  Product release Assays Under GMP  Lot release testing  Stability Support  Dose formulation analysis  Manufacturing monitoring  Process improvement

Support for Various Therapeutic Areas Oncology Diabetes/Metabolic CNS Inflammatory Infectious Disease Toxicity

Supporting Transgenic Plant Protein Analysis

The BioAgilytix Difference  Expertise  Quality  Transparency  On time  On budget A Very Simple Commitment To All Of Our Clients

Preclinical- Clinical vs. Manufacturing Assay Needs

Need for an Ideal Platform  A common theme throughout drug development is to “ do more with less ” and reduce the cost of drug development.  Assay laboratories must harness potential synergies between technology platforms, innovative optimization approaches, robotics, software programs , and LIMS .

Plan Ahead Are the Reagents and Instrument Available by All? Can Everyone Be Trained on the Platform? Pharmaceutical and biotechnology companies spend lots of time and money developing sensitive and robust assays Most CROs offer ELISA and RIA

Choose an Ideal Platform To Support Your Project An Ideal Platform is One That is Applicable Through All Stages of Drug Development Process Clinical Discovery And Manufacturing And Post Marketing Preclinical

Regulatory Requirements Different Levels of Regulation May Be Required for Each Step Of the Drug Development Process Laboratory GMP Scale, GMP-Like Pre-Clinical Material Manufacturing Clinical Material Manufacturing Post Discovery Preclinical Clinical Marketing Non-GLP Spirit-of- Spirit-of- GLP GLP Non-GLP Spirit-of-GLP GLP GLP GLP

Bioanalytical Requirements Different Analytical/Bioanalytical Requirements May Be Needed for Each Step Of Drug Development Post Discovery Preclinical Clinical Marketing Assay range Intra- and inter-batch precision Intra- and inter-batch accuracy Specificity Selectivity Dilutional linearity LLOQ and ULOQ Short/long-term, and F/T stability

Platform Versus Instrument

Immunoassay Instrument Market  7 Billion Dollars Market  Over 85 companies Play in this market:  Abbott Laboratories  Beckman Coulter  Biomerieux  Bio-Rad Laboratories Inc.  Roche Diagnostics  Siemens Healthcare Diagnostics  Ortho-Clinical Diagnostics

Platform Versus Instrument Platform measureable output (Technology) (signal) Instrument Conversion of signal into (Tool) interpretable information

Platform Versus Instrument (cont.) One platform in one instrument Multiple platforms in one instrument

Preclinical-Clinical VS. Manufacturing Assay Needs Preclinical-Clinical Manufacturing Platform Parameter (Discovery-GLP) (GMP) Sensitivity ++++ ++ Precision ++++ Dynamic range ++++ ++ Matrix interference ++++ ++ Robustness and ruggedness ++++

Preclinical-Clinical VS. Manufacturing Assay Needs (Cont.) Preclinical-Clinical Manufacturing Platform Parameter (Discovery-GLP) (GMP) Total assay time +++ ++ Multiplexing ++ + Throughput +++ + Adaptability to automation ++ ++ Ease of implementation ++ ++

Preclinical-Clinical VS. Manufacturing Assay Needs (Cont.) Preclinical-Clinical Manufacturing Platform Parameter (Discovery-GLP) (GMP) Cost of implementation ++ ++ Instrument routine operation +++ Physical characteristics of an + + instrument Service and Maintenance +++ Software ++

Current Immunoassay Platforms and Instruments

Existing Immunoassay Detection Modes  Absorbance  Photon counting  Refraction index  Combination

Existing Immunoassay Detection Molecules  Iodine-125  TMB, HRP  Luminol  Europium chelate  Ruthenium chelate  Fluorescein  Alexa Fluor  Label-free

Existing Immunoassay Platforms  Radioactive  Colorimetric  Fluorescence  Luminescence  Luminescence Proximity Assay  Electro-chemiluminesence  Time Resolved Fluorescence  Time-Resolved Fluorescence Proximity  Fluorescence Polarization  Surface Plasmon Resonance  Imaging

RIA • Developed in the 1950s by R. Yallow and S. Berson. • Known concentration of radio-labeled antigen competing with antigen in sample for binding to antibody. • Very sensitive Gamma Counter • Requires special precautions and licensing

ELISA / FIA • Most Common immunoassay platform since early 1970s • Many reagent and instrument providers • 0.5-2 day assay • 1-2 log dynamic range • Matrix effect

DELFIA • Dissociation Enhanced Lanthanide Fluorescence Immunoassay • Plate-based ELISA with lanthanide fluorophore detection • Large Stokes Shift results in low background • Multiplex up to 4 labels – Europium – Samarium, – Terbium – Dysprosium

HTRF • Homogeneous Time- Resolved Fluorescence • Time-Resolved Fluorescent Resonance Energy Transfer (TR-FRET) • Excited energy of europium is transferred to allophy- cocyanine (APC)

AlphaLISA • Bead-based ELISA • Mix and Read • No wash • Need 1-2 biomarker antibodies for development • Improved acceptor beads have a tighter emission range

MSD-ECL • MesoScale Discovery Electrochemiluminescence • 3-4 log dynamic range • Sensitivity in low pg/ml range • Detection Mode: • Electrochemiluminescence • Measurement of light emitted from excited Ruthenium fluorophore.

SearchLight • Imaging system • Chemiluminescence • 2-min read time • Image of entire plate at once SignaturePLUS ™ Analyzer

GYROS • Fluorescence Based Assay • AlexaFluor 647 Dye • Use of Micro-fluidics • Fast development • Requires limited sample volumes • Fully automated system

Singulex • Fluorescence + Flow Cytometry • Use of magnetic beads • Single molecule reading • Fully automated system • Very sensitive • Measuring low level proteins

Luminex • The bead populations are detected using a 635 nm laser and they are identified based on the ratio of proprietary dyes found in the beads. • The captured analytes are detected using a 532 nm laser which is used to excite the fluorochrome phycoerythrin (PE) that is attached to a detection reagent

LICOR • Imaging system • Near-IR Dyes: IRDye 800CW and IRDye 680LT • Extremely low background • Many appliations: • Immunoassay • Cell based assay • Western blot

American Association of Pharmaceutical Scientists: 21 st Century Lab Characterization and Supply of Critical Reagents for Ligand Binding Assays BioAgilytix, Centocor/J&J, BMS, Genentech, Pfizer/Wyeth, Amgen, Genzyme, Biogen, Radix Biosolutions, Mesoscale Discovery, Millipore, ThermoFisher Ligand-Binding and Immunoassay Platforms: Balancing Innovation with Business Risk BioAgilytix, Amgen, Bristol-Myers Squibb, Biogen Idec, Genentech, Radix BioSolutions, Midwest BioResearch, Gyros, PerkinElmer, Molecular Devices, Mesoscale Discovery

American Association of Pharmaceutical Scientists: 21 st Century Lab The 21 st Century Lab: Automation of Ligand Binding Assays BioAgilytix, Amgen, Roche, Thermo fisher, Genentech, Xyntek, Radix Biosolutions eSolutions: Electronic Laboratory Data Management BioAgilytix, Amgen, Genentech, Indigio Bio, Novartis, Radix Biosolutions, Wyeth, Molecular Devices

Preclinical-Clinical Studies and Manufacturing Processes Bring With it a Set of Bioanalytical Having assay Requirements and Platforms That Associated Challenges Meets the Required Regulatory and Assay Needs is the Key to Success

Questions?

Jim Petrilla Afshin Safavi, Ph.D. Mike McCartney President & CEO VP, Business Development VP, Bioanalytical Operations james.petrilla@bioagilytix.com afshin.safavi@bioagilytix.com Michael.McCartney@bioagilytix.com 919.381.6163 919.381.6164 919.381-6097 ext. 219