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Juliette van den Dolder, PhD CEO

The solution in 3D cell culturing

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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

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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.

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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 organs 2D cell culture ware

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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

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The solution: synthetic hydrogel PIC hydrogel

hot cold

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

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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 .

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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 Stiffness After 4 days

Neuron Myoblast Osteoblast

Huebsch et al. Cell 2006, 126, 677

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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

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RUO products Diagnostic products Therapeutic products

2016 2018 2021 2026

Sales & marketing Product development

R&D + product development Sales & marketing

R&D + product development Sales & marketing

Business model & Market approach

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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%.

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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

- - + - +

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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