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Viral Vectors:finding the good in everyone

A global and integrated offer from vector developmentto final product release:

> Process transfer, development, optimization, scale-up and validation> Assays transfer, development and validation> Small to large scale manufacturing> Upstream, downstream and aseptic Fill & Finish> Pre-clinical, clinical and commercial applications> Wide range of Viral Vectors manufactured (AAV, Lentivirus, Adenovirus, HSV, VSV...)

Viral Vectors can contribute to transform lives of patients with severe diseases:Novasep, as a reliable , is committed and proud to be part of this rewarding challenge by offering a support to your clinical & commercial manufacture of Viral Vectors.

A strong track recordA strong track record

FINDING THE GOOD IN EVERYONEFINDING THE GOOD IN EVERYONE

Our specific know-how in a wide range of Viral Vectors includes: AAV, Lentivirus, Adenovirus, HSV, VSV, VEEV... for cell & gene therapy, CAR-T, immunotherapy, vaccination and other therapies.

produced and released by Novasep in the last 5 years.

For 20 years, Novasep has acquired experience in the development and manufacturing of biomolecules.

Senrise-IV, our commercial production facility

Senefill, our new commercial facility for aseptic Fill & Finish

Senrise-IV is dedicated to the production of your Viral Vectors.

To support the launch of your product, Novasep has opened a new commercial facility for aseptic Fill & Finish operations: Senefill.

Our commercial solutionsOur commercial solutions

• 2 independant cGMP manufacturing lines • USP & DSP• Suspension and/or adherent modes• Up to 2,000L scale• Commissioned in Q1 2019• Seneffe, Belgium

Guided tourGuided tour

>150 cGMP

BATCHES

• A full state-of-the-art facility • Fully automatic filling under isolator• Up to 10,000 vials per session• Filling of Viral Vectors, plasmids

and other biologics (mAbs, proteins...) • Stand alone services as well as integrated

drug product manufacturing• Commissioned in H2 2019• Seneffe, Belgium

Guided tourGuided tour

A complete offering including transfer, development, optimization and validation.

Our clinical solutionsOur clinical solutions

Downstream processing (DSP)• Large set of purification technologies: chromatography, TFF, filtration...• Scalable up to 1,000L

Production servicesProduction services

Upstream processing (USP)Adherent mode• Disposable support CS10/HS36 • Fixed-bed bioreactors (e.g.: iCELLis®)• Microcarriers in bioreactors

Suspension mode• Batch, fed-batch & perfusion• Disposable technology• Scalable up to 1,000L

Novasep has a fully dedicated plant for Fill & Finish (F&F) offering flexibility for standard & custom services. Our dedicated team can also provide stand alone services.

• Semi-automatic or automatic filling• Hundreds to 4,000 vials per session• Customizable (volume, stoppers, vials)• 2mL to 100mL vials • Filled volume: 0.25mL to 100mL

F&F servicesF&F services

Our 2 sites in BelgiumOur 2 sites in BelgiumSeneffe: clinical and commercial productionGMP: USP, DSP & F&FQC labs Mid- to Large scale up to 2,000L

Gosselies: clinical productionProcess & Analytical development GMP: USP & DSP Small to Mid- scale up to 200L

EASY ACCESS AND IN THE HEART OF BELGIUM’S LARGEST BIOTECH HUB:

• 5 minutes from Charleroi airport • 1-hour from Brussels or Lille airports• 20 minutes by car between our 2 sites

Following its recent investments with Senrise-IV and Senefill, Novasep has launched a unique 2-year turnkey plant offer to accelerate commercial production of Viral Vectors.

oXYgeneoXYgeneTM A fully integrated offer for Viral Vector production

• Parternship solution• Design, construction and operation of customer dedicated facilities• 2 years • On Novasep sites• Senefill: plant ready to serve oXYgeneTM customers

Key informationKey information

DRUG PRODUCT RELEASED

BY NOVASEP QUALIFIED

PERSON

Enjoy the visit

BELGIUMGERMANY

NETHERLANDS

FRANCE

LUXEMBOURG

GOSSELIESSENEFFE

BRUSSELS

AsiaNovasep Asia+86 21 6045 1600

EuropeNovasep+33 437 282 030

North AmericaNovasep, LLC+1 610 494 0447

Rest of the worldNovasep+33 437 282 030 03

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© 2019 Groupe Novasep SAS. Groupe Novasep SAS and/or its affiliates (hereafter Groupe Novasep) own or license the copyrights, trademarks, names, logos, and other rights to the information in this brochure. No right or license is granted to any other losses for access or reliance and not from access. Any unauthorized use without the express prior written consent of Groupe Novasep is prohibited. Disclaimers: The information contained in this brochure are provided “as is”, for informational purposes only, without any representation or warranty of accuracy or completeness. In no event will Groupe Novasep be liable to any party for any damages or any other losses from access or reliance upon any information contained in this brochure.

Services and technologies for the life science industries

www.novasep.com

Viral Vectors CapabilitiesViral Vectors CapabilitiesMODE PERFORMANCE SUITES DESIGN

Clinical facility, manufacturing suites

for small to mid-scale production

Suspension using bioreactors ranging from 50L to 200L

Adherence mode in CS10 or HS36

Up to 4 productions in parallel

8 suites Grade C production suites with operations under grade B

Modular area

cGMP multiprocess/ multiproduct facility Clinical facility,

manufacturing suites for mid

to large-scale production

Suspension using bioreactors ranging from 50L to 1,000L

Adherence mode in CS10 or HS36

Up to 2 productions in parallel

3 suites

Senrise-IV, commercial facility

Suspension and/or adherent modes

Up to 2,000L scale (USP and DSP)

2 cGMP manufacturing lines Grade C production suites with operations under grade B

Clinical Fill & Finish facility

Semi-automatic or automatic filling

From hundreds of vials up to 4,000 vials per session

1 suite

Grade B aseptic suite with operations under grade A

(RABS)

Senefill, commercial Fill & Finish facility

Automatic filling under isolator

Up to 10,000 vials per session

1 suite

Grade C aseptic suite with operations under

grade B and grade A (isolator)

Contact our experts: cmo.biopharma@novasep.com

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NOVASEP HAS PRODUCED NUMEROUS CLINICAL GRADE BATCHES OF AAV’S DIFFERENT SEROTYPES, USING BACULOVIRUS/SF9 AND TRANSFECTION TECHNOLOGIES, IN BOTH ADHERENCE AND SUSPENSION MODES.

Parental virus is apathogenic

Long-term expression of the transgene

Episomal vector

Low immunogenicity

Transduce non-dividing & dividing cells

Numerous serotypes with different tropisms

Low DNA packaging capacity (4.5kb)

Empty vector particles generated during the manufacturing process

Pre-existing immunity

Highly resistant vector particles

AAV Vectors:finding the good in everyone

AAV Serotype Production System Process Production scale Project Clinical stage(s)

Recombinant AAV1HeLa

SuspensionSTR

AdV Helper Up to 1 000L SUB PD Phase III

Recombinant AAV2HEK293Adherent

CS10Transient transfection 24CS10

PD & cGMPDS & DP

Phase I, II & III

Recombinant AAV3HEK293

iCELLis® 500Transient transfection iCELLis® 500

PD & cGMPDS & DP

Phase I/II

Recombinant AAV5HEK293Adherent

CS10Transient transfection 24CS10

PD & cGMPDS & DP

Phase I/II

Recombinant AAV8HEK293

SuspensionSTR

Transient transfection 200L SUBPD & cGMP

DS & DPPhase I/II

Recombinant AAVrh10

HEK293Adherent

CS10Transient transfection 24CS10

PD & cGMPDS & DP

Phase III

sf9 Baculovirus infection 200L SUBPD & cGMP

DS & DPPhase I/II

20+ CLINICAL BATCHES PRODUCED... AND STILL COUNTING

Drawbacks

Various genetic eye diseases

Cystic fibrosis

Haemophilia

Cancer

AAV PROFILE

Benefits

Applications CNS

And many others...

Did you know?Did you know?

NOVASEP HAS PERFORMED 5 PROJECTS BASED ON ADV, ESSENTIALLY FOR ONCOLYTIC APPLICATION UP TO THE SCALE OF 50L IN BIOREACTORS.

Benefits Drawbacks Ensure high level of transgene expression

Transduce non-dividing & dividing cells

Larger cloning capacity

Tumor-targeted replication of specifically designed oncolytic adenovectors

Vector particles produced at high titer

Highly immunogenic

The vector genome does not integrate into the host cell genome

Transient transgene expression only

Pre-existing immunity (AdV5)

Risk of inflammatory response

Type Production System Process Application Project Clinical stage(s)

Oncolytic AdV5HeLa

SuspensionPerfused STR

Infection CancerPD, scale-up

& cGMPDS & DP

Phase I/II10L STR

Chimeric Oncolytic AdVHEK293

SuspensionSTR

Infection CancerPD, scale-up

& cGMPDS & DP

Phase I/II50L STR

ADV CLINICAL BATCHES PRODUCED... AND STILL COUNTING

ADENOVIRUS (ADV) PROFILE

Adenovirus Vectors:finding the good in everyone

Cancer therapy (oncolytic AdV)

Vectorized vaccines

Applications

Did you know?Did you know?

NOVASEP HAS PERFORMED MORE THAN 30 PROJECTS ON DIFFERENT TYPES OF OTHER VIRAL VECTORS, INCLUDING HSV, VEEV, EITHER IN SUSPENSION OR IN ADHERENCE MODES.

Type Production System Process Application Project Clinical stage(s)

Recombinant Measles VirusMRC5CF10

Infection VaccinecGMP

DS & DPPhase I/II 24CF10

Oncolytic undisclosed VirusHeLa

SuspensionSTR

Infection CancerPD, scale-up

& cGMPDS & DP

Phase I/II 50L SUB

Recombinant VEEV(Venesuelian Equine Encephalitis Virus)

VEROAdherent

CS10

Transfection by electroporation

VaccinecGMP

DS & DPPhase I/II

CS10

Recombinant VSV(Vesicular Stomatitis Virus)

VERO Adherent

CS10Infection Vaccine

cGMPDS & DP

Phase I/II15CF10

Recombinant VSV(Vesicular Stomatitis Virus)

VERO Perfused STRmicrocarriers

Infection VaccinePD, scale-up

& cGMPDS & DP

Phase I/II50L SUB

PD in progress

Recombinant HSVVERO

AdherentHS36

Infection CancerPD & cGMP

DS & DPPhase I/II15HS36

Attenuated Influenza Virus (A/H1N1, H3N2, H5N1 & B)

VEROAdherent

CF10Infection Vaccine

PD & cGMPDS & DP

Phase I/II 15L / 15CF10

Recombinant DengueVEROSTR

microcarriersInfection Vaccine

PD & scale-up

DS

Pre-clinical50L SUB

Oncolytic H1 virusHuman T-cells

Wave BRInfection Cancer PD, USP

Pre-clinical25L Wave

Baculovirus vectors encoding VLP or recombinant protein

Sf9 or Hi-5Suspension

STRInfection Vaccine

PD, scale-up & cGMPDS & DP

Phase I/II 10L & 50L SUB

Wild type HIV (BSL3)Human T-cells

STRInfection Vaccine

PD, scale-up

Phase I/II 50L SUB

30+ CLINICAL BATCHES PRODUCED... AND STILL COUNTING

Other Viral Vectors:finding the good in everyone

Mainly vectorized vaccines

Oncolytic vectors

Rec. proteins: sub-unit vaccines, mAbs, ADCs, conjugates, cytokines, various therapeutical proteins

Applications

Did you know?Did you know?

NOVASEP HAS PRODUCED MORE THAN 40 BATCHES OF LENTIVECTORS BASED ON HIV-1 AND ON EIAV (EQUINE), IN BOTH ADHERENCE AND SUSPENSION MODES.

Benefits Drawbacks Long-term expression of the transgene

The vector genome integrates into host cell genome

Low immunogenicity

Transduce non-dividing & dividing cells

VSV-G pseudotyped LV have a broad host-cell range and confer a high particle stability

DNA packaging capacity relatively limited (10kb)

Possible insertional mutagenesis

Enveloped particles are poorly resistant, which makes their storage, production and purification difficult

Few pseudotypes available (mainly VSV-G)

Type Production System Process Application Project Clinical stage(s)

Lentiviral vectors based on EIAV

HEK-293TAdherent

CF10Transient transfection Gene Therapy

cGMPDS & DP

Phase I/II 24CF10

Lentiviral vectors based on HIV

HEK-293TAdherent

CF10 & HS36Transient transfection Vaccine

PD, scale-up & cGMPDS & DP

Phase I/II25L / 25CF10

120L / 15HS36

Lentiviral vectorsHEK-293T

SuspensionTransient transfection Gene Therapy

PD, scale-up & cGMPDS & DP

Phase II/III50 and 200L STR

40+ CLINICAL BATCHES PRODUCED... AND STILL COUNTING

LENTIVECTOR PROFILE

Lentivirus Vectors:finding the good in everyone

Correction of inherited genetic defects

Cancer immunotherapy via CAR-T cell therapy

Applications

Did you know?Did you know?

Learn more about

AAV, Lentivirus, Adenovirus and HSV vectors in our dedicated publications including case studies!