Insights from a Global Collaboration Accelerating Vaccine Development with an Optimized VLP Platform

Merck KGaA
Darmstadt, Germany
Naomi Baer
Business Development Consultant
Process Solution
Youssef Gaabouri
Associate Director & Head of Sales
Middle East and Africa
Process Solution
Building strong technical partnerships
Insights from a Global Collaboration
Accelerating Vaccine Development
with an Optimized VLP Platform
Jose M. Galarza, Ph.D.
CEO & President
TechnoVax Inc.

2
The Life Science business of
Merck KGaA, Darmstadt, Germany
operates as MilliporeSigma
in the U.S. and Canada.
Collaborating to improve vaccine accessibility | May 2022

0 Youssef Gaabouri
1
0 Naomi Baer
2
0 José M Galarza
3

➢ Innovative Biotech
➢ Advanced Biotech Grant Winner
➢ Technical collaborations – Product Development
➢ Small Scale to Commercial Scale
➢ Product confirmation qualification results
➢ Next Steps for VLP Vaccine
➢ Our Integrated Offering
Outline

Local vaccine players in Africa, most producing
limited volumes(< 1% of local needs)
Most of the local production is focused on
distribution, fill & finish of Drug Product(DP)
“Routine platforms” (egg based, bacterial,
inactivated or attenuated viral vaccines) present in
Egypt, North Africa, Senegal.. South Africa
Strong support from public institution (Institut
Pasteur).
Africa vaccine area and main players (2020)
6
Manufacturing of the Drug Substance and/or have some of the
manufacturing value chain steps
Small API and / or High interest of entering in a local Manufacturing
phase
No production
Source: Capital IQ, Press search, Companies websites, VMPA study

Local strategy : 3 models for expanding manufacturing capacity
7
0 12 24 36
Elapsed time in Months
72
48
Budget
100 Millions €, excluding Clinical trials if applicable and tech transfer for bulk. Assumptions: Green field project.
Routine
production
Fill & Finish
Outbreak
platform model
Short
Term
Long
Term
> 72
Model Description
Reverse integration of fill & finish activities
with imported bulk(DP). Usually it starts with
packaging & labelling using existing
filling/storage capacity. Could be greenfield
project. Bulk provider is key
Expansion of existing manufacturing sites for
drug substance manufacturing. Few eligible
sites in Africa (Egypt, Senegal, North& South
Africa mainly..). High CAPEX & regulatory
challenges
New facility using novel platform modalities
(mRNA, VLP..). Lower CAPEX due to process
optimized & efficiency. Able to manage multi-
vaccine type and give fast answer in case of
pandemic episodes
˜

Our company & Innovative Biotech
Approach
Establish a strategic plan with high level
commitment
Existing of building Filling capacity: Help to make a
valuable business model for DP and prepare DS
manufacturing via Life Science Service & Process Solutions
divisions : from conceptual design to Plant construction.
Know-How, Tech transfer: Use our company process
capabilities: Process Dev., Process optimization..
People, Training: Connect the dots with our company’s
Network and Reliable partners. Propose a training plan
Building viable ecosystem
8

Our company Collaborates with Innovative Biotech
Nigeria – TechnoVax US to Support Establishment of
First Vaccine Production Facility in Nigeria
Our company to accelerate self-sufficient
vaccine development and manufacturing in
West Africa
This collaboration is part of the West African
pandemic readiness program, which
aims to localize vaccine development in the
African nations
9 19-APR-2022 Africa Council meeting

EB Grant Program
Our 2019 winner is …
11 Collaborating to improve vaccine accessibility | May 2022
TechnoVax, Inc.
VLP TECHNOLOGY
❖ Adenovirus(multivalent)
❖ Influenza
❖ RSV
❖ Zika
❖ Dengue
❖ COVID-19

• Virus-like particles (VLPs) are biological nanoparticles composed of
viral structural proteins, frequently major proteins in the capsid or
envelop.
• Contain repetitive high-density displays of viral surface proteins that
elicit strong immune responses.
• Self-assemble into structures morphologically resembling viruses.
• No genetic material – no replications, non-infectious.
• 20 to 200 nm in size and is similar to the size of the corresponding
viruses, allows them to be taken up by dendritic cells (DCs) and
antigen-presenting cells (APCs).
• Can be produced in a variety of cell culture systems, against
different strains of a virus other than those for which the vaccine
was formulated.
• They sometimes require adjuvants to increase their immunogenicity
• Proven technology (Hepatitis B and Human Papillomavirus licensed
vaccines)
Virus Like Particles (VLPs) have the shape of virus
but no genetic materials, good immune response & no risk of pathogenicity
13

Cell culture Clarification
Nucleic acid
digestion
Sterile
filtration
Final
Formulation
HEK-293 Suspension cell line
Cell culture media & supplements
Upstream chemicals
Single-use bioreactors
Sterile Filtration
Biosafety testing
Product characterization
Validation services
Master Cell Banking
Benzonase®
endonuclease
Mixers
Chromatography
Ion exchange
chromatography
resins
Membrane-based
chromatography
Single-use systems &
multi-use skids
Buffers
Mixers
Storage assemblies
Biosafety testing
Validation services
Tangential flow
filtration
Buffers
TFF cassettes
and capsules
Single-use
systems & multi-
use skids
Mixers
Storage
assemblies
Validation
services
Sterilizing
filters
Housings
Integrity testers
Storage
assemblies
Sterile
connectors
Sampling
solutions
Validation
services
Excipients
Bioavailability
enhancers
Buffers
Storage
assemblies
Sampling
solutions
Biosafety testing
Validation
services
Make Purify Formulate
Buffers
Depth filters
Pleated filters
Single-use systems
Validation services
Assure
Final Fill
Single-use final
fill assemblies
Storage
assemblies
Biosafety
testing
Validation
services
14
 * viral clearance unit operation applicable for only AAV vector production
Virus Like Particles (VLP) Production

VLP Process Template Bench Scale
Sterile Filtration Formulation chromatography Ultrafiltration
Cell Culture DNA Digestion Clarification Bioburden Reduction

VLP Process Template 500L Scale – Mobius® Single-use Systems
Cell Culture 3L 50L Bioreactor 200L / 100L Bioreactor DNA Digestion Clarification
Phase 1 Final Fill Facility Ultrafiltration
Chromatography Steps
Phase 2 Manufacturing Facility
17

Facility Design, Build & start up
Full support for SCALABLE
PROCESS DEVELOPMENT
Proven, ready to use, single-use
USP/DSP template at < 2kL
Integrated Single-Use process
Media Buffers & CIP
Pre-clinical Ph I Ph II Ph III Commercial
USA Bulk Fill Finish Nigeria Commercial
Designing & validating an entire
single-use process
USP/DSP Process
development TOOLBOX
18

 Defined process for
production and
purification of SARS-
CoV-2 VLPs
• Confirmed formation
of VLPs by electron
microscopy
• Identified presence
structural proteins in
purified VLPs by
Western Blot
• Assessed
immunogenicity of
VLP vaccination in
mouse model and
analyzed functional
antibody response by
pseudovirus
neutralization assay
Defined
process
Confirmed
formation
Identified
presence
1 2 3 Assessed
immunogenicity
4
Summary of Work in Progress

Western Blot Analysis of Purified VLPs
Anti-Spike
~180 kDa
Anti-Matrix
~25 kDa
Anti-Nucleocapsid
~55 kDa
190
115
80
70
50
30
25
15
190
115
80
70
50
30
25
15
190
115
80
70
50
30
25
15
kDa
:
kDa
:
kDa
:
Collaborating toimprove vaccine accessibility | May 2022
21

Electron microscopy images of SARS-Co-2 virus-like particles (VLP) negatively stained with phospho-tungstic
acid (A-C) and Immunogold labeled anti-spike (D)
A B C
D
SARS-CoV-2 Virus-Like Particles
22

16 32 64
128
256
512
1024
2048
4096
8192
0.00
0.25
0.50
0.75
1.00
1.25
VLP + Alum
Dilution Factor
Absorbance
(450
nm)
Pre-Immunization
Spike Immunized control
VLP + Alum
1
6
3
2
6
4
1
2
8
2
5
6
5
1
2
1
0
2
4
2
0
4
8
4
0
9
6
8
1
9
2
0.00
0.25
0.50
0.75
1.00
1.25
VLP + SNP
Dilution Factor
Absorbance
(450
nm)
Pre-Immunization
VLP + SNP
1
6
3
2
6
4
1
2
8
2
5
6
5
1
2
1
0
2
4
2
0
4
8
4
0
9
6
8
1
9
2
0.00
0.25
0.50
0.75
1.00
1.25
VLP + AddaVax
Dilution Factor
Absorbance
(450
nm)
Pre-Immunization
VLP + AddaVax
1
6
3
2
6
4
1
2
8
2
5
6
5
1
2
1
0
2
4
2
0
4
8
4
0
9
6
8
1
9
2
0.00
0.25
0.50
0.75
1.00
1.25
VLP only
Dilution Factor
Absorbance
(450
nm)
Pre-Immunization
VLP
Immunization with SARS-CoV-2 VLPs
Yields S-Specific Antibodies
23

SARS-CoV-2 VLP Vaccine
Comparison of Neutralization of Beta and Delta Variants
24
Neutralization of Beta Variant Neutralization of Delta Variant
A B
COVID-19 VLP vaccine immunization of mice produces high levels of neutralizing antibodies
against both Beta and Delta variants of SARS-CoV-2.
V
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S
10
100
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ID
50
✱✱
✱✱✱
✱
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Comparison of Neutralization of Beta and Delta Variants
25
Neutralization of Beta Variant Neutralization of Delta Variant
C D
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✱
✱ ✱
✱✱✱
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✱
✱

Neutralizing Activity Against Beta Variant Correlates with
Neutralizing Activity Against Delta Variant
26
Neutralization of Beta and Delta Variant
E
V
L
P
+
A
l
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m
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a
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P
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VLP + Alum Female
VLP + Alum Male
VLP + SNP Female
VLP + SNP Male
VLP + AddaVax Female
VLP + AddaVax Male
VLP Female
VLP Male
0 1000 2000 3000 4000 5000
0
1000
2000
3000
4000
5000
Beta Variant ID50
Delta
Variant
ID
50

Next Steps for
SARS –CoV-2 VLPs
Vaccine

• Efficacy study
• Wild type Syrian hamster
model
Looking forward
• Phase I Clinical Trial
• Passive transfer study
• ACE2 transgenic mouse
model
Coming soon for VLP based COVID-19 Vaccine

1
Clinical trials for this
vaccine candidate
are being conducted
in Ghana, Nigeria,
and South Africa –
Set to be
completed in Q3
2022
Next Steps for Global project
2
Production of the
VLP vaccine will be
conducted initially in
the US while the
facility in Nigeria is
being constructed
3
Production will be
transferred to
Nigeria for Fill &
Finish following
clinical trials (Q4
2022) –
Full production by
Q3 2023
4
In the short-term,
utilize the platform
to develop a vaccine
for HIV/AIDS, which
impacts a large
portion of the
African population
5
Establish domestic
vaccine
manufacturing
capabilities with a
robust template in
Nigeria to serve the
African community
29

Collaborations
PRICELESS!
What is the value we’re bringing
INTEGRATED SOLUTIONS to our customers
Extensive Life
Science portfolio &
Services
Know-How
Resources
Personal network
Internal network
One stop shop
Open partnership

Innovative Biotech LTD
Simon Agwale, Ph. D
West African Health
Organization
Sybil Nana Ama Ossei-
Agyeman-Yeboah
• Ryan Mazboudi
• Jose M. Galarza, Ph.D
• Ke Wen
• Matthew Resch
• Hannah Mulhall
• Kaitlyn Garvey
• Brandi Brone
• Sohal Shah
TechnoVax Inc.
Our Company
• Naomi Baer
• Claire Scanlan
• Thomas Elich
• Tyler Cheung
• Youssef Gaabouri
• Mochao Zhao
• Carole Inglevert
• Alexandra Steele
• Meghan Rozell
• Patrick McGee
• Jerome Dalin
• Joel Ngoje
City College University
of New York
• Paul Gottlieb
• Reza Khayat
• Jorge Morales
• Alexandra Alimova
Acknowledgements
32

For more information about Vaccine Production:
please visit SigmaAldrich.com/Vaccine-manufacturing
Thank You! Questions ?
Millipore, SAFC, BioReliance, Emprove, Benzonase, Mobius and the vibrant M are trademarks of Merck KGaA, Darmstadt, Germany or its affiliates. All other
trademarks are the property of their respective owners. Detailed information on trademarks is available via publicly accessible resources.
© 2022 Merck KGaA, Darmstadt, Germany and/or its affiliates. All Rights Reserved.

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