Lab Pilot and Process Chromatography Systems Sepragen Corporation

Lab, Pilot and Process Chromatography Systems Sepragen Corporation Confidential Sepragen Property 1

Downstream Products Mission To provide breakthrough products that enable faster production and lower cost development and manufacture of life saving biological drugs. Values We bring our unbridled innovative spirit in service of you, the customer. We will reach for products and solutions that will help you develop and manufacture life saving drugs rapidly and cost effectively within the framework of compliance. We operate with a spirit of fairness, integrity, teamwork and mutual respect. We deliver what we promise. Sepragen Corporation 2

Sepragen Corporation Innovators in Bioprocessing • Sepragen has provided state of the art bio-processing technology to the biotech companies for over 25 years. Holds 16 patents. • Sepragen focused on processing of bio-processing: • Inventors of Radial Flow Chromatography • Quantasep Chromatography Systems and Skids • Quantasep 3000 SU Single use Chromatography Systems • Sepraflo Single Use Ion Exchange Resins • QS Buffer Dilution System • The purification products are already used in the biotech industry at Amgen, Baxter, GSK in FDA approved drug manufacture. • Twenty + FDA approved drugs and over 200 global installations. • Current Products address a served market in excess of $10 Bn Sepragen Corporation confidential 3

Our Customers The “Who’s Who” of Pharma and Biotech 4 confidential

Downstream Products Radial Flow Chromatography Columns Quanta. Sep Chromatography System Quanta. Sep SU system with disposable flowpath 4 X Faster than Competitive Columns Automate and run separations with 50% less footprint and 2 X capacity Small Footprint No Cleaning Validation Rapid changeover between batches Sepragen Corporation confidential 5

Sepraflo Resins 4 X better price performance than competition Customized Chromatography Skids Scaling capabilities New Downstream Products in Launch In-Buffer Dilution System Reduce Plant Footprint Capex & FTEs Confidential Sepragen Property Sepragen Corporation 6

Why choose Sepragen’s Quantasep Systems? Flexibility, Ease and Innovative Compact c. GMP Design § Hardware – Fully Integrated system – Compact foot-print – Real time air ejection – Leak Detect – multimode detector – Pump stall feed-back § Software – Intuitive method builder – Easy P&ID Control – Comprehensive reports – Chromatograms & analysis Sepragen Corporation Confidential Sepragen Property 7

Precision Rotary piston pumps with stepper motor control • Positive displacement • Stepper motor control • No check valve for good clean-ability • Low pulsation • Small displacement/ rev= even flow Sepragen Corporation 8

Pump Features • Positive displacement (Ceramic piston and lining) • Stepper motor control • No check valve for good clean-ability • Low pulsation • Small displacement/ even flow 9 Sepragen Corporation

Superior Gradient Performance. Quantasep 1000 100: 1 Turn down ratio on pumps Sepragen Corporation 10

Cleaning Validation Study • Process: • Inoculate • Incubate • Wash in Na. OH • Water Wash • Swab at test 31 points Sepragen Corporation 11

Results of Microbial challenge study on Quantasep 1000 Location S. Aureus E. Coli P. Aerg. C. Albicans A. niger Inlet A 0 0 0 Inlet B 0 0 0 Pump A 0 0 0 Pump B 0 0 0 Manifold A 0 0 0 Manifold B 0 0 0 Pressure 0 0 0 Mixer 0 0 0 Col Outlet 0 0 0 Col. Inlet 0 0 0 Bypass In 0 0 0 Bypass Out 0 0 0 UV flow cell 0 0 0 Cond. sensor 0 0 0 0 0 p. H Ref 0 0 0 Fraction comm 0 0 0 Fraction 1 0 0 0 Air Outlet 0 0 0 Air Inlet 0 0 0 Sepragen Corporation 12

Benefits of Quantasep’s Auto Air Ejection system Auto Air Ejection n. Protects against dilution of Product n. No Unnecessary Gradient formation n. Provides Protection of Column from any amount of air n. Can be used to detect end of sample Bubble Trap n. Causes Dilution of Product n. Unnecessary Gradient formation n. Doesn’t provide Protection of Column large air incursion n. Increases Hold Up volume Manual air valve Air Outlet Air Ultrasonic air sensor Flow Out Flow In 3 way valve Flow in Flow Out Sepragen Corporation 13

• Reduce Hold Up Volume • Minimize mixing of step change buffers • Improve Cleanability • Minimize sample loss in bubble trap Elution Peak with Sepragen Active Air Ejection as compared to conventional Bubble Trap Sepragen Corporation 14

Lab Quantasep Product Line: Quantasep 100 and 1000 Models: Integrated, compact, rugged and sanitary systems • Hardware Feature Set: Quantasep 100 • Two Pumps (Rotating Piston, positive displacement) • 12 inlets and 10 fractions • 3 columns • Forward flow, reverse flow and bypass • UV, p. H, temp and Conductivity detection • Sensors for pressure, air, leak and rpm check • Stainless Steel Fluid-handling compartment • Biocompatible materials of construction • Outputs for remote data logging • Fraction collector interface trigger • Emergency pause Quantasep 1000 Sepragen Corporation 15

Quantasep 1000 LXLab, Pilot and Production Scale Systems: • Quanta. Sep 1000 LX Dual Flow Capabilities: • Quantasep 1000 LX • • Quantasep 1000 LX has dual flow-paths: 0100 ml/min and 0 -1000 ml/min; Run in either mode by simply clicking on QSep 100 or Qsep 1000 c. GMP mode on Start-Up Screen Quantasep 1000 LX ideal Scale Up system • Do PD work with 0 -100 ml/ min flow-path • Use with up to capabilities to work with bioreactors from 3 L to 20 L Quantasep 1000 LX c. GMP sanitary desgn • Run in c. GMP mode with large flow-path with 21 CFR Pt 11 software • Quantasep 1000 LX Sepragen Corporation Quantasep 1000 LX 16

Quanta. Sep 1000 LX vs Akta Avant 150 and Akta Pilot Features Qsep 1000 LX Akta Avant 150 Akta Pilot 600 Comments/Options Bench top Yes Yes Quantasep has smaller footprint Flow-paths per system Two One Quantasep 1000 LX covers greater flow rate range than two independent Aktas combined (column sizes 5 ml to 10 L) Sanitary Design yes No Yes (partial) Akta Avant is not sanitary and will not work for c. GMP (uses threaded fittings) and rotary valves. Quantasep is sanitary, no threaded fittings, all diaphragm valves Sample injector yes No In Quantasep sample loops are standard Detectors UV, Cond, p. H, air, pressure All sensors standard. In Quantasep 1000 LX two UV wavelengths (280 and 260 nm)are standard rather than 3 for GE. Akta uses it to stop flow not like the Quantasep 1000 LX which removes air dynamically. Pumps 4 2 2 2 Pumps are standard. With Quantasep 1000 LX no pump priming is required. Buffer Selection 6 x 2 +6 x 2 6 x 2 for either system 4 x 2 and 4 x 2 Six buffer selection valves are standard on each pump in Quantasep Fraction Collection 10 standard outlets and Optional FC Yes for Akta Avant 150 No, only 6 outlets Quantasep 1000 LX fraction. Sepragen collector has. Corporation 10 standard outlets and FC with up to two trays can be provided as 17 an option. Triggered by Quantasep software

Quanta. Sep 1000 LX vs Akta Avant and Akta Pilot Hardware Qsep 1000 LX Akta Avant Akta Pilot Benefits Turndown Ratio of Pumps 100: 1 30: 1 Greater dynamic range Typical Flow Range for each pump 0 -100 ml/min and 101000 ml/min 10 -150 ml/min 20 -600 ml/min Akta Avant 150 cannot accurately do under 10 ml/min and Akta Avant 25 is needed. Akta pilot cannot do over 600 ml/min, Akta Process is needed. One Quantasep 1000 LX system can do under 10 ml/min to 1 pm i. e. smaller and bigger columns than either and both GE systems put together Gradient (at 50% FS) 5 -95% 10 -90% Quantasep 1000 LX has a 100: 1 turn down ratio so better gradients are possible at lower flowrates Online Buffer Dilution Yes Yes Better dilution accuracy System Dead (hold up) Volume 7 ml small flow path and 120 ml for large flow-path ~10 ml 500 ml Better chromatography, less dilution, better gradient, lower peak volume Footprint 22”x 27”x 46” 30”x 60”x 72” 30’x 60’x 72” Quantasep system has smaller footprint than either Akta Auto Air Ejection Electronic ( NO) Bubble trap (NO) Bubble trap Akta does not use auto bubble ejection; bubble trap difficult to clean, cannot use with gradient, causes dilution Leak Detection Yes No No Akta systems do not alarm or stop run in Sepragen Corporation event of leak. Especially dangerous with high 18 flow like Akta Pilot

Advantages of Quanta. Sep Software vs Akta Avant 150 and Akta Pilot 600 Software Features Quantasep 1000 LX GE Akta Avant GE Akta Pilot Benefits Point and Click Operation from Process Diagram Manual Operation Yes No No Easier usage, more intuitive interface; Less training time Auto programming of methods Yes Yes Buffer selection; Flow setting; step and fraction switch conditions based on time, volume, bed volume, UV slope, p. H, Cond, Air, pressure, time and UV 21 CFR Pt 11 compliance software with encrypted database, journal, secure multilevel access Yes Yes Quantasep has all standard features found on Akta Chromatogram and data analysis Yes, in real time Yes, post run only Quantasep marks peaks during run and provides peak AS, HETP, % Area, multiple sensor trends, run overlays for comparison, zoom, pan, configurable y axis for all sensor ranges and x axis for time, volume etc. ; gradient plots Auto Pause, manual intervention; zero UV base line, begin run marker, sample injector bypass Yes Yes Quantasep software is capable of all such tasks that Akta can do Gradients, manual and auto Yes Sepragen Corporation Yes Quantasep has Up to 10 step or linear segments

Lab, Pilot and Production Scale Quantasep Systems: Quantasep 1000 LX, Quantasep 1800 and Quantasep 5000 Models • Quanta. Sep 1000 LX Capabilities: • Quantasep 1000 LX • Quantasep 1800 Capabilities • • Quantasep 1000 LX has dual flow-paths: 0100 ml/min and 0 -1000 ml/min; Run in either mode by simply clicking on QSep 100 or Qsep 1000 c. GMP mode on Start-Up Screen Run 100 L/hr are in a compact, bench top c. GMP sanitary system, perfect for 250 L 500 L bioreactor Quantasep 5000 Capabilities • Run upto 300 L/hr with a mobile c. GMP system sanitary system , Perfect for 500 to 2000 L bioreactors • Quantasep 5000 Sepragen Corporation Quantasep 1800 20

Lab, Pilot and Production Scale Quantasep Systems: Quantasep 1000 LX, Quantasep 1800 and Quantasep 5000 Models • Quanta. Sep 1000 LX Capabilities: • Quantasep 1000 LX • Quantasep 1800 Capabilities • • Quantasep 1000 LX has dual flow-paths: 0100 ml/min and 0 -1000 ml/min; Run in either mode by simply clicking on QSep 100 or Qsep 1000 c. GMP mode on Start-Up Screen Run 100 L/hr are in a compact, bench top c. GMP sanitary system, perfect for 250 L 500 L bioreactor Quantasep 5000 Capabilities • Run upto 300 L/hr with a mobile c. GMP system sanitary system , Perfect for 500 to 2000 L bioreactors • Quantasep 5000 Sepragen Corporation Quantasep 1800 21

Lab, Pilot and Production Scale Quantasep Systems: Quantasep 1000 LX, Quantasep 1800 and Quantasep 5000 Models • Quanta. Sep 1000 LX Capabilities: • Quantasep 1000 LX • Quantasep 1800 Capabilities • • Quantasep 1000 LX has dual flow-paths: 0100 ml/min and 0 -1000 ml/min; Run in either mode by simply clicking on QSep 100 or Qsep 1000 c. GMP mode on Start-Up Screen Run 100 L/hr are in a compact, bench top c. GMP sanitary system, perfect for 250 L 500 L bioreactor Quantasep 5000 Capabilities • Run upto 300 L/hr with a mobile c. GMP system sanitary system , Perfect for 500 to 2000 L bioreactors • Quantasep 5000 Sepragen Corporation Quantasep 1800 22

Inside Look at Quantasep 10000 (10 lpm) Chrom Systems • Compact, easy to service design • Muli-headed dual PD pumps • Sanitary construction • Pneumatic single block diaphragm valve manifolds • All necessary sensors Sepragen Corporation

Custom Skids 5 LPM and 30 LPM • Open Frame, easy to service design • Pneumatic control, constant pressure operation • Sanitary construction • Pneumatic single block diaphragm valve manifolds • All necessary sensors Sepragen Corporation 24

2 5 Purification of MAb using 250 ml RFC packed with Protein A media on Qsep 100 system • Column size: 250 ml RFC • Resin: MAb Select • Flow rate: 100 ml/ min • Titer: 4 gms/l • Load: 1. 75 L (7 gms) • Recovery: 92% • Processing Time: 45 min Sepragen Corporation

Customizable Quantasep Open Skid Configuration • Customized Open Architecture: Mobile skid construction with user specified number of valves, pumps and pre and post column sensors for air, flowrate, pressure, conductivity, UV and p. H • Operational up to 50 psi • Gradient and isocratic capability • Easy Access to Fluid components for serviceability • Optional plastic or 316 L SS Flow-path • Optional Hazex standard of construction for flammables liquids • Complete TOP, FAT, SAT, IOQ and commissioning and Installation • Software PLC/SCADA/ C# uses encrypted database and is 21 CFR Pt 11 compliant • Can interface via OPC to Delta V, Foxboro, Siemens, Schneider, Allen Bradley confidential 26 Sepragen Corporation

Project Management • URS Definition with Client • Preliminary Design • P&ID • Design • General Arrangement • Solid Modeling • Electrical Schematics • Software Screens • Design Review • Procurement • Fabrication • Sub-Assembly • SA Testing • Assembly Testing • Functional Testing • Documentation (IOM, TOP) and Tagging • Crating and Ship • SAT • Install and Commissioning • On-going PM Sepragen Corporation

Case Study 10 ml/min c. GMP system From concept through design, fabrication and installation • Skid for Commercial Botox mfg • Created FRS by getting seemingly conflicting input from Engr, Mfg, Safety, PD and IT • Got convergence by recommending an open frame fluid-handling skid coupled by a nitrogen purged electrical enclosure operating inside a hood with gloves for access and fumigation and exhaust capability • Computer and HMI outside hood Sepragen Corporation

Custom Quantasep Process Chromatography Skids at GSK, Novartis, Neose • Gradient 2 Pump 10 -40 Liter per minute per pump, 5 -95% Gradient • 10 Inlets, 2 Outlets, Filter, Bubble Trap, Column fwd, Rev & Bypass • Pre and post column p. H and Cond sensors, Multi wavelength UV • Sanitary 316 L SS Piping, 304 SS Moblie Ex Proof Skid • Air sensor, Auto air removal and Bubble Trap with control system • Leak sensor, Pressure Sensor • Filter, Flow through and Bypass • CE, BASEEFA (class 1 Div 1, T 4) Certified ATEX explosion proof skid Sepragen Corporation

QS Chromatography System (1000 LPH) with IBD Chromatography using 10 X concentrated Buffers § Full Chromatography Functionality including Manual and Auto operation, gradients, UV, sensors, valves, c. GMP reports, chromatograms and analysis capability § Four Pumps for sample/ WFI, Concentrates, acid and base; 2 Flow meters, 3 p. H sensors, 2 conductivity sensors and one UV sensors § Total Flow Accuracy +/- 1% actual flow or 0. 3% FS § Composition Accuracy +/- 2% or 0. 5% FS § p. H Control +/- 0. 1 p. H § Footprint 34” x 27”x 50” Sepragen Corporation confidential 30

3 1 QS Buffer Dilution System • Capabilities • Flow rates 5 lpm to 30 lpm • Footprint 30” x 27”x 42” • 110 V and 90 psi instrument quality air • Total Flow Accuracy +/- 3% actual flow or 0. 3% FS • Composition Accuracy +/- 5% or 0. 5% FS • p. H Control +/- 0. 1 p. H Confidential Sepragen Property Sepragen Corporation

Performance: On-line Buffer Dilution Skids Concentrate 20%(5 X) 10%(10 X) 5%(20 X) Sepragen Corporation confidential 32

QS Column Packing System LX • PC Driven Automated packing system • Reproducibility and consistency of packing • Different recipes for different columns and resins • Automated air removal, Slurry packing, bed stabilization and bed integrity testing • c. GMP documentation of column qualification • Batch record reports and electronic storage Sepragen Corporation confidential 33

Single Use Flow-path Quantasep Systems Sepragen Corporation 34

Quantasep 3000 SU S. S Fluid Handling Module • • • Bench top System Dual Pump System Quick disconnect fittings Easily wipe- downable c. GMP suitable Sepragen Corporation

Quantasep 3000 SU- Single Use • Ergonomic Design • Touch- screen built in computer & keyboard • Easily removable front and side panels • Removable flow- path Sepragen Corporation

Quantasep 300 SU 100/ 300 ml/min system Inside look at the flow-path (1. 6 mm and 3. 2 mm) UV sensor flowcell Peristaltic Pumps A & B Inlet Valves Manifolds A &B Pressure sensor Pre-column Device (bubble-trap/ filter) Lines to and from column p. H sensor Air sensor Flowmeter Fraction Valve Manifold Conductivity Sensor Quick Disconnect Fittings Sepragen Corporation

3 8 Quantasep- Single Use Flowpath • • • First Single Use bench top system No Cleaning Validation time Down time between batches minimized Remove tubing path and flow cell Easy Change –over Low cost of system and flowpath Sepragen Corporation

39 Critical Software Features of the Quantasep Software n WINDOWS 10 Based SOFTWARE PLATFORM n Intuitive method builder n Pt. and Click Manual and Auto Dashboard Control n Event and Alarm Log n Gradients and Buffer Dilution n Comprehensive run documentation and report n Trending and Data Analysis n 21 CFR Pt. 11 Compliance software n Security n Data Export Confidential Sepragen Property Sepragen Corporation

Manual Operating Screen • Simply Click on valves to select buffer, fraction and flow direction • Enter flowrate values near pump icon • Run Manual linear or step gradients from screen • Go through or bypass precolumn filter • For lab systems, inject sample manually or through sample loop • Monitor all sensors values Sepragen Corporation 40

Software Features Easy operation, monitoring& control • Operation from graphical P&ID screen • Manual or Automated Modes • Unlimited Recipes with buffer and fraction changes based on time, volume, bed volumes, sensor values, air, pressure • Real-time Chromatogram with all sensor and flow variables with settable and autoadjust ranges • Linear and step gradients • Constant Flow and Constant Pressure Operation • Real time event and alarm log for pressure, air and leaks • Manual Intervention in auto runs • Auto air eject • On-screen calibration of pumps and sensors • Chromatogram Analysis of HETP and Asymmetry Sepragen Corporation 41

Operating SCREENS For Auto Run AND Chromatogram Sepragen Corporation

Peak Identification and analysis Sepragen Corporation

4 4 Librarian for easy filing, retrieval and management of methods and run data Sepragen Corporation

Intuitive Method Builder n Tabular Excel type format - eliminates the hassle of programming n Step changes on time, volume, bed volume, air, UV Slope, Air, % Peak Max, and Combined Variables n Automatic method validation Sepragen Corporation 45

Conductivity Sensor Calibration using the Quantasep Software Sepragen Corporation 46

Sensor Calibration from Quantasep Software Sepragen Corporation

Qsep Auto Gradient Run Sepragen Corporation

Real time overlays of Multiple Chromatograms Sepragen Corporation

Reports n. Validation 4 track alarms, events, notes and any manual changes n. Automatic analysis report n. Calibration Report 4 Calibration data 4 Time between calibrations n. Method and column information Sepragen Corporation 50

Calibration History and Report Sepragen Corporation 51

Password controlled security system More Software Features Chromatogram replay and zoom capabilities Linear or step gradient programmability Generic file formats for easy export Settable alarm conditions Built-in audit tracking capability Sepragen Corporation 52

53 Summary § Precision Engineered Sanitary Chromatography Systems § 100: 1 turn down ratios extend usability across small and large columns § Small Footprint can ensure usability in small suites § Buffer Dilution capability save space and FTE § 50% less Hold up volumes ensures better quality product and easy cleanability § Documentation for compliance § Easy to use and train Sepragen Corporation confidential