GREATER ACCESS & AUTONOMY
through innovation in bioproduction
Confidential presentation
Vaccine Technology Summit 2023
Cambridge, MA
20 MARCH 2022
Compact mRNA Production through
Process Intensification & Innovation

2
mRNA Production
TODAY

3
Conventional mRNA production: uniformity in variety
https://doi.org/10.3390/biomedicines10010050 DOI: 10.13140/RG.2.2.34118.80966
https://repository.upenn.edu/cbe_sdr/132
https://doi.org/10.1016/j.trsl.2021.11.009
https://doi.org/10.1021/acs.iecr.2c01217

4
Conventional
mRNA
production:
uniformity
in variety
n
INCUBATION TFF CHROMATOGRAPHY TFF
• Facility footprint
• Acquisition of individual production systems:
– Investment
– Need for installation, commissioning,
qualification of each
– Available equipment scales vs. (GMP!) process
needs?
PROCESS INFRASTRUCTURE
• Batch operation: system idle time, transfer of
intermediates between unit steps (➜ process hold,
operator intervention, increased total process
duration…)
• Several UF / DF operations ➜ volume of TFF
buffers, process waste
• Cumulative loss of material over DSP = decrease in
yield
PROCESS OPERATION
PROCESS SUPPLY
• Long bill of materials: complex supply chain
management, vendor qualification & control,
QC requirements
• Many suppliers = many failure points
PROCESS DEVELOPMENT
• Development of custom or generic (“template”)
mRNA process
• Process optimization, characterization, qualification -
including mixing of process solutions, storage of
prepared solutions and intermediates,
chromatography resin lifetime studies…
• Process scale-up from R&D to mass scale
INCUBATION
CHROMATOGRAPHY TFF
Implications

5
mRNA Process
Intensification &
Innovation

6
Building Ntensify™
the start of the
Nfinity™ platform

7
In partnership with
Width System: 2065 mm
Height System: 2400 mm
Width Chamber Opening: 1950 mm
Height Chamber Opening: 600 mm
User Interface: 560 mm
Depth System: 786 mm
Batch Size: up to ~5 g (~ 12 h operation)
Weight: 840 kg
LAF Flow Rate: 0.45 m/s
Integrated Particle Counter

8
USP DSP

9

10

11

12
The power of process intensification and innovation
GMP
1 3
Upgrade
Mini Maxi
Midi
2
R&D
• Optimized, generic process
• Ready-to-use reaction mixes
• No scale-up (scale-out / scale-in-time)
• One fully automated, integrated system
• Easy installation
• Limited facility impact (small Grade D / ISO 8 room)
• Lower COGS

13
Our upstream process consistently delivers a high yield of capped
mRNA transcripts and low impurity levels…
YIELD
Reactions: 245
Constructs: 45
4.0
7.2
CAPPING
EFFICIENCY
Reactions: 111
Constructs: 19
87.5
97.9

14
Our upstream process consistently delivers a high yield of capped
mRNA transcripts and low impurity levels…
RESIDUAL
DNA
Reactions: 39
Constructs: 6
0.03
29.5
dsRNA
CONTENT
Reactions:
UTP: 83; mUTP: 36
Constructs:
UTP: 36; mUTP: 31
38.9
397.4
75.8
727.0

15
Our upstream process consistently delivers a high yield of capped
mRNA transcripts and low impurity levels…
1166 bases
4284 bases 1999 bases
2080 bases
3979 bases
4060 bases

16
… requiring minimal downstream processing with minimal product losses
73.5
106.1
YIELD
Runs: 28 | Constructs: 3
0.82
1.09
INTEGRITY
(PRE/POST)
Runs: 22 | Constructs: 3
0.2
1.1
RESIDUAL
PROTEIN
Runs: 19 | Constructs: 3

17
What’s NEXT?

18
Quantoom’s Nfinity™ platform:
from sequence to formulation
NfinityTM Platform
RNA
Synthesis
RNA
Purification
Encapsulation &
Formulation
DNA
Linear DNA
Fill &
Finish
Nplify Ntensify Ncapsulate
mRNA Workflow

THANK YOU
for your attention!
19