Presentation by Juliëtte van den Dolder from Noviocell; From technology to business. During SMB meeting on December 15, 2016 at SMB Life Sciences / Novio Tech Campus in Nijmegen, NL.

1. 1
Juliette van den Dolder, PhD
CEO
The solution in 3D cell culturing

2. 2
Noviocell, spin-off from Radboud
• Spin-off: founded Nov 2015
• Prof A. Rowan, Dept Molecular Chemistry,
RU Prof W. Feitz & Dr E. Oosterwijk, Dept
Urology, RIMLS, Radboud UMC
• Our mission is to accelerate life science
research in (stem) cell growth and
differentiation by making 3D cell culture
feasible for every (stem) cell biology
researcher.
• Polyisocyanopeptide (PIC) hydrogel is a fully
synthetic biomimetic extracellular matrix
with identical biomechanical properties as
natural matrices

3. 3
Challenge: Lack of effective cancer therapies
• For example, there is no adequate cure for pancreatic cancer at the
moment and the survival rate of pancreatic cancer is extremely low,
estimated around 3-6 % after 5 years.
• The use of organoids is considered to be the solution to accelerate the
development of new therapies for pancreatic cancer.
• Organoid technologies have significant potential as effective patient
avatars
• Tumor organoids and matching
normal organoids identify associations
between: oncogenic drivers, gene-drug
interactions, efficacy of drugs and
other therapies
Cerebral organoid
M. Lancaster et al.

4. 4
Stem cell researchers need 3D scaffold to mimic
human nature
• 3D mini-organs or organoids for diagnostics or personal medicine
• Currently, natural ECM materials like mouse tumor derived
scaffolds or bovine collagen are used
3D human organs2D cell culture ware

5. 5
Natural gels cannot be used for clinical
applications
Drawbacks Natural matrices (Matrigel)
Batch to batch variation - their exact composition
cannot be defined
Pathogen transmission and immunogenicity
Technical challenges in handling - difficulties in cell
or organoid isolation
Technical challenges with downstream processing
after culturing - imaging
Experimental inertness - inability to experimentally
vary composition
Due to their composition, they cannot be used for
clinical applications

6. 6
The solution: synthetic hydrogel PIC hydrogel
hotcold
Advantages of PIC hydrogel
No batch to batch variation – because of
synthetic origin
Excellent cell growth and differentiation
Biomechanical properties similar to
natural matrices - same elasticity as
collagen
Easy to use - reversible thermosensitive
no difficulties in cell or organoid isolation
& no difficulties with down stream
processing or imaging after culturing
Biofunctionality - make your own
functional hydrogel by clicking your
growth factor of choice to the polymer
Biodegradable and non-toxic

7. 7
Mimic architecture of Extracellular Matrix
A. Representation of the hydrogen-bond network that stabilizes the secondary
helical structure of the PIC.
B. The structure of the PIC hydrogel visualised with atomic force microscopy.
C. Comparison of the stiffness of PIC vs. different natural matrices as a function of
stress .

8. 8
Stem cells respond to extracellular matrix
Discher et al. Science 2009, 324, 1673; Yamada et al. Cell 2006, 126, 645.;
R. Das, O. Zouani Biomaterials 2014, 35, 5278.
Substrate StiffnessAfter
4 days
Neuron Myoblast Osteoblast
Huebsch et al.
Cell 2006, 126, 677

9. 9
Increasing critical stress in polymer gels (P1 to P6)
Lipid droplets in cells (indicating adipogenic commitment) by Oil
Red O staining (Scale bar: 10 µm)
hMSCs commitment analysis after 4 days
Experiment indicates preferential adipogenesis in gels with lower critical stress; gels with
higher critical stress favor osteogenesis
Das RK, Rowan AE. Nat Mater.2015

10. 10
RUO products Diagnostic products Therapeutic products
2016 2018 2021 2026
Sales & marketingProduct development
R&D + product development Sales & marketing
R&D + product development
Sales &
marketing
Business model & Market approach

11. 11
The current market is dominated by Matrigel®
Matrigel:
 ±70% market share (market share> 95% scientific
publications)
 Worldwide revenue ± €160M
3D cell culture market:
• is worth €433 million in 2015, estimated to reach €1.5
billion by 2024 with a CAGR of 14.8%. Scaffold-based
technologies account for a revenue share of over 40%.

12. 12
PIC hydrogel the best alternative for Matrigel
Analysis of synthetic competitors
Puramatrix Hystem Mebiol Hydromatrix Noviogel
Synthetic + + + + +
No chemicals or
enzymes
- - + - +
No crosslinking + - + + +
Tune able strain
stiffness
- - - - +
Tune able
biofunctionality
+ - - - +
Reversible
thermosensitivity
- - + - +

13. 13
Take home message
Contact details:
Juliette van den Dolder
+31 (0)6 46155064
j.vandendolder@noviocell.com
Reinier Postlaan 2
6525 GC Nijmegen
The Netherlands
• PIC hydrogel is an innovative
solution for 3D cell culture and
future clinical applications
• Innovative product in a fast
growing market that are
unmatched by our
competitors