Patient MonitoringEngraftment / PersistenceDisease Status BiomarkersToxicity Biomarkers (CRS)

Apheresis │ Tissue Biopsy

Gene T

rans

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Formulation

Cell SeparationLineage DeletionCell SelectionPopulation Verification

Cell CultureActivation Expansion Differentiation

Quality ControlCell Marker Expression Validation Secretion Profile Validation Product Purity Examination

Pioneering Cell and Gene Therapy Solutions From Discovery to the Clinic

Your vision is to create revolutionary cell and gene therapies to treat life threatening diseases. Bio-Techne and its family of brands is on this journey with you. As a full-solution ancillary reagent and services provider, we will stand by you, providing flexible and pioneering tools to simplify your workflow. From CAR T cells to pluripotent stem cells, let us help you get your therapy to the patients that need it!

Our goal is to provide innovative and flexible solutions that expedite the path of your cell therapy from the laboratory to the clinic. Our ancillary reagents, raw materials, and automated analytic instrumentation provide the framework to confidently build out ex vivo manufacturing procedures. The following five attributes are at the core of our cell and gene therapy mission:

• Innovative Solutions We are invested in creating reagents and technologies that improve the standard of manufacturing, qualification of products, and monitoring of cell therapies.

• Scalability Experienced manufacturing and quality systems at Bio-Techne will ensure that our GMP reagent supply meets your requirements for scale-up.

• Flexibility and Customization Our flexibility extends into GMP custom services for media, proteins, and antibodies. Our reagents are compatible with all closed system technologies, and no challenge is beyond our ability to help.

• Consistency and Reproducibility We apply stringent quality standards to all our cell therapy tools. We guarantee lot-to-lot consistency and proper documentation for every GMP reagent we produce, so you can be confident your process will be reproducible, compliant, and traceable.

• Reduced Risk We are developing cell therapy manufacturing products to help you reduce the risk to patients. We follow GMP regulatory frameworks, and we are re-defining the standard of reagent design.

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visit bio-techne.com/cgt

GMP ancillary and raw materials must provide robust performance in cell manufacturing workflows. With our focus on quality, innovation, supply chain continuity, and traceability, Bio-Techne® GMP-grade reagents are the reliable solution for your cell culture expansion, activation, and differentiation protocols (see boxes, page 4).

• GMP proteins

• GMP small molecules

• GMP media production

• GMP Cloudz™ T Cell Activation Kit

Custom Solutions

Learn about our custom services for cell therapy ancillary and raw materials, including GMP proteins, Cloudz™ kits for cell activation, and cell culture media.

visit bio-techne.com/cgtculture

5′-N

ucle

otid

ase/

CD73

100

101

100

102

103

104

101 102 103 104

Negative Marker Cocktail-PE Negative Marker Cocktail-PE

Negative Marker Cocktail-PE

CD90

/Thy

1

100

101

100

102

103

104

101 102 103 104

Endo

glin

/CD

105

100

101

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102

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101 102 103 104

Stem Cell Characterization with the Human Mesenchymal Stem Cell Verification Flow Kit (Catalog # FMC020).

Obtaining and qualifying a robust starting cell population is the essential first step for an ex vivo manufacturing workflow. By coupling innovative cell selection technologies with robust flow cytometry antibodies for cell qualification, Bio-Techne is creating a new standard for cell separation.

• Multi-color flow cytometry kits for identification of cell lineages and subsets

• Custom-developed Cloudz™ cell separation services

Custom Solutions

Efficient workflows often require customized solutions. Put our decades of experience to work for you. View our custom services for cell therapy ancillary and raw materials, including cell separation.

visit bio-techne.com/cgtseparation

Cell Separation & Characterization

Cell Culture

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Pioneering Technologies for Cell Culture

Pioneering Cell and Gene Therapy Solutions From Discovery to the Clinic

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GMP Cloudz™ T Cell Activation Kit

GMP-grade Ancillary Reagents

A major advance in cell activation technology

• Dissolvable microparticles conjugated with anti-CD3 and anti-CD28 antibodies

• Robust T cell activation and expansion

• Release buffer dissolves particles in < 10 seconds

• Simplified recovery of cells – no beads to remove from cell culture!

• Customizable with other antibodies and proteins for your process

Small Molecules We are the exclusive source of GMP-grade small molecules! Let us help you develop the next stem cell therapy.

• Y-27632 (ROCK inhibitor) enhancing stem cell survival and viability

• SB 431542 (TGF-b RI inhibitor) differentiation and reprogramming protocols

• CHIR 99021 (GSK-3 inhibitor) differentiation and reprogramming protocols

• DAPT (g-Secretase inhibitor) neuronal differentiation protocols

• XAV 939 (Tankyrase inhibitor) cardiomyocyte differentiation protocols

GMP Small Molecule Testing

Purity

Product identification

Water content

Residue on ignition

Residual solvents

Solubility

Bioburden

Endotoxin

Complete Documentation

• Batch-to-batch consistency

• Certificates of Analysis, Certificates of Quality, TSE/BSE Statements

• Equipment maintenance and monitoring records

Recombinant Proteins Often our GMP proteins originate from the same clone, sequence, and expression system as our traditional research grade materials. This makes the switch to GMP as seamless as possible.

• IL-2, -3, -4, -6, -7, -12, -15 • Activin A, FGF basic, Noggin, SCF • And many more … an industry-leading selection of nearly 50 GMP proteins!

visit bio-techne.com/cgtculture

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Luminex® Assay Confirmation of Embryonic and Induced Pluripotent Stem Cell Differentiation. Simultaneous quantitation of 11 key analytes that are upregulated during hepatocyte lineage differentiation.

Fc A

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Direct-labeled Proteins for Confirmation of CAR Expression. Antigen recognition of an anti-CD19/EGFP CAR construct was shown by specific binding of Recombinant Human CD19-Fc Chimera Protein labeled with Atto-647N (left) or unlabeled CD19 (right).

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y = 0.3645x + 224.12R² = 0.9963

Sim

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TM A

ssay

(pg/

mL)

Quantikine® ELISA (pg/mL)

Human TNF-α16000

35000 40000

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y = 0.512x - 82.78R² = 0.999

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Quantikine® ELISA (pg/mL)

Human IFN-γ25000

40000 50000

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y = 0.4662x - 1.2368R² = 0.9896

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mL)

Quantikine® ELISA (pg/mL)

Human IL-1β250

400 500

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0Sim

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ssay

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Quantikine® ELISA (pg/mL)

y = 0.6364x + 47.411R² = 0.9814

Human IL-63000

3000 3500 4000

2500

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1500

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1000

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500

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Correlation Between Immunoassay Platforms for Smooth Transition to Automated Biomarker Testing. High-throughput Simple Plex™ assays are calibrated to their respective Quantikine® ELISA kits during development.

A safe and consistent cell therapy product requires stringent, sensitive, and standardized assays to document purity and quality. Our pioneering technologies allow you to generate reliable and accurate quality control data while ensuring your cell therapy gets to the clinic as fast and as safe as possible.

• Cell Characterization

• Flow Cytometry Antibodies

• Immunoassays

• Product Purity

Custom Solutions

Explore our custom services for cell therapy, including antibodies and multi-analyte immunoassays.

visit bio-techne/cgtquality

Quality Control

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Pioneering Cell and Gene Therapy Solutions From Discovery to the Clinic

Pioneering Technologies for Quality ControlElla and Simple Plex™ AssaysElla is an automated ELISA platform that is ideal for in-process and release testing for cell therapy products. Ella provides unparalleled accuracy, reproducibility, and speed for characterizing cytokine secretion profiles.

• Customizable multiplex cartridge options

• Nearly 200 validated assays

• 21 CFR Part 11-compliant

visit bio-techne.com/cgtquality

Description Specification

Sample Volumne Required 2.5 to 25 µL

Analytes per Sample Up to 4 independent Simple Plex assays per sample

Throughput 72 samples with 1 analyte, or 16 samples with up to 4 analytes

Hands-on Time 5 minutes

Time to Result 60 minutes

Sensitivity Sub-picogram/mL

Reproducibility Single-digit CVs, results in triplicate

Dynamic Range 4–5 logs

Cross-reactivity N/A, Simple Plex assays are run in parallel in individual channels

Automation. Ella runs immunoassays in a microfluidic Simple Plex cartridge. Everything is pre-loaded on the cartridge — even the calibration curve! All you need to do is add your sample and buffers and put the cartridge in Ella.

Reproducibility. Testing across 3 sites, 11 users, 9 Ella instruments, four different assays, and 8 unique serum samples with 2 controls for a total of 704 answers.

Sandwich immunoassays happenin the Glass Nano Reactor (GNR)

Sample

Fluorescent Label

dAb Target/SampleCapture Ab

GNRs

GNRs

Waste dAb-4

dAb-3

dAb-2

dAb-1

FluorRunningBuffer

1 Sample is routed through microfluidic channels.

2 Capture antibody captures target analyte.

3 Stringent wash removes unbound analyte.

4 Detection antibody migrates through microfluidic channel.

5 Stringent wash removes unbound detection antibody.

6 Scan GNRs.

Multi-Site Test(All Results Histogram)

1.5

CV = 7.5%

1.4

1.3

1.2

1.1

1.0

0.9

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0.7

0.6

0.5

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The Dynamic Range of Simple Plex™ Assays enables quantitation of multiple analytes in CAR T cell donor serum with a single dilution factor. The sub-picogram sensitivity allows detection of fainter signals than other assay platforms.

Simple Plex™ Assay Quantitation of Biomarker and Cytokine Levels for Disease Monitoring. Multianalyte detection in serum samples facilitates evaluation of lung disease status in asthma, pneumonia, lung cancer, and COPD patients.

Tracking the clinical safety and efficacy of a cell therapy requires sensitive and fast systems. Ella and Simple Plex™ assays are making real-time monitoring of immune responses a reality (see Box, page 6). Our Simple Plex assays cover dozens of cytokines involved in the cytokine storm as well as these disease status biomarkers:

•Adiponectin/Acrp30

•alpha-Fetoprotein/AFP

•CA125/MUC16

•C-reactive protein/CRP

•Cytokeratin-18

• D-dimer

• Galectin-3

• HE4/WFDC2

• HIV Gag p24

• Mesothelin

• MMP-9

• PCSK9

• PD-L1

• Pentraxin-3/TSG-14

• Periostin/OSF-2

• ST2/IL-33 R

Patient Monitoring

Simple Plex™ assays automate the quantitation of analytes in less than an hour.

For even greater flexibility of biomarker monitoring, our Luminex® assays measure up to 50 analytes simultaneously, from a menu of over 450 analytes.

visit bio-techne/cgtmonitoring

Certification and regulatory guidelines followed for GMP reagents

• Proteins are manufactured in our ISO 9001:2015, ISO 13485:2016-certified facility.

• Small molecules are manufactured following a quality system based on ICH Q7 guidelines.

• USP Chapter <1043>, Ancillary Materials for Cell, Gene, and Tissue-Engineered Products

• USP Chapter <92>, Growth Factors and Cytokines Used in Cell Therapy Manufacturing

• Ph. Eur. General Chapter 5.2.12, Raw Materials of Biological Origin for the Production of Cell-based and Gene Therapy Medicinal Products

Range of Observed Sample Values in CAR T Donors vs Healthy Controls

IL-10

CAR T Sample Range

IL-6 TNF-α IL-15 IP-10

0.1

1

10

100

1000

10000

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mL)

Normal Sample Range Assay Range

Analyte Name LLOQ (pg/mL)

ULOQ (pg/mL)

Average Intra-Assay

Average Inter-Assay

Average Linearity

Very High AbundanceTotal Adiponectin 20.9 51540 8.9% 6.5% 99%CRP 4.55 50550 3.1% 3.7% 102%High AbundanceCD14 16.7 2830 9.7% 7.3% 105%Chitinase-3 Like 1 5.10 52610 6.6% 10.0% 90%MPO 1.57 18530 6.9% 9.2% 102%Medium-High AbundanceE-Cadherin 25.4 14860 3.1% 10.3% 101%E-Selectin 3.80 14020 6.2% 9.0% 93%MMP-8 37.2 9950 9.3% 12.0% 109%ST2 39.10 28180 2.4% 7.7% 98%Medium AbundanceBAFF 1.05 9970 7.2% 7.9% 91%HGF 5.69 15160 7.1% 5.4% 102%IL-2 Ra 3.14 3920 5.6% 7.9% 86%RAGE 3.37 6180 7.0% 9.0% 95%TNF RI 0.80 2980 5.2% 10.9% 99%TNF RII 1.41 2260 4.5% 7.7% 98%Low-Medium AbundanceMIG 13.5 15590 8.2% 10.7% 101%VEGF A 4.84 4490 5.5% 6.7% 107%Low AbundanceIL-6 0.41 3850 3.2% 7.7% 115%IL-8 0.80 2470 5.8% 6.9% 104%IL-13 4.13 13720 3.6% 6.5% 92%TNF-a 1.14 2900 5.0% 4.7% 111%Very Low AbundanceIL-4 0.32 1290 7.5% 11.0% 109%IL-5 0.07 3120 6.5% 9.2% 98%IL-10 0.46 5530 5.3% 7.1% 111%IL-15 0.46 1950 6.9% 5.6% 90%

LLOQ= Lower Limit of Quantification ULOQ= Upper Limit of Quantification

Analytical Performance Characteristics for the Simple Plex™ Platform

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Global info@bio-techne.com bio-techne.com/find-us/distributors TEL +1 612 379 2956North America TEL 800 343 7475 Europe | Middle East | Africa TEL +44 (0)1235 529449China info.cn@bio-techne.com TEL +86 (21) 52380373

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For research use or manufacturing purposes only. Trademarks and registered trademarks are the property of their respective owners.

Bio-Techne and its family of world-class brands offer an unbeatable array of pioneering technologies for Cell and Gene Therapy. We are committed to spurring advances in Cell and Gene Therapy manufacturing with our top-quality reagents, instruments, and services.

>1,700 RECOMBINANTANTIBODIES

NEARLY150 KNOCKOUT-VALIDATED TARGETS

26 FLUORESCENTDYES FOR CONJUGATION

>200 STEM CELLCOMPOUNDS

60 MINUTES TIME TO RESULT FOR SIMPLE PLEX

>200 VALIDATEDSIMPLE PLEX ASSAYS4-5 LOG DYNAMIC RANGE

FOR SIMPLE PLEX ASSAYS

SINGLE-COPYRNA DETECTION

NEARLY 50 GMP-GRADE PROTEINS

UNMATCHED IMMUNOASSAY PLATFORM RANGE

GMP CELL CULTUREMEDIA PRODUCTION

NEW PROBES DESIGNEDIN 2 WEEKS

>30 YEARS OFEXPERIENCE

USED BY ALLTOP 20 GLOBAL PHARMACOMPANIES

X20

1ST GMP SMALL MOLECULESFOR STEM CELL THERAPY

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