Providing single use bioreactors for the modern age

Business Model

Cellexus makes a range of disposable bioreactors

for the production of recombinant proteins from bacteria, yeasts and Mammalian cells.

BiopharmaceuticalsFood additives

CosmeticsBiofuels

Worldwide sales dynamics

Increasing trend towards use of disposables

Cost savingsReduced downtime

Reduced risk of contamination

Cost comparisons

stainless steel

single use

-30%Electricity -38%

Space

-62%Steelwork

-87% Water

-95%CleaningMaterial

Reference: Sinclair A, et al 2008. The environmental impact of disposable technologies. BioPharm International Supplements.

Worldwide sales

2013 2014 2015 2016 20170

100

200

300

400

500

600

700

Worldwide market for GMP Disposable Biore-actors ($m)

WW Marketsize

Worldwide sales (fermentation)

21032014

20152016

2017

0

50

100

150

200

250

Disposable fermentation reactor market worldwide $m

CellMaker

Touchscreen User interface

Communications + sensor readers

Gas supply + Mixing + temp control

RegularPlusFelix

8L & 50L sizes

Sterile single-use bags

How it works

Competition: Microbial

These customer driven USPs are evident upon comparison against competitor products in the field of microbial cell culture:

Ease of Use

• Sterile bag prevents cross contamination

• Simple set up and simple to use

• High OTR

• Accurate temperature control using Peltier plates

• Increased performance using enriched air

• Reduced and easily defined costs

• Small footprint

• Fast changeover

Technical Information

CellMaker systems – flexible layout

Step 1 – Menu screen

Step 2 – change parameters

CellMaker PLUS Controller: Software

14

CellMaker Applications

CellMaker REGULAR Applications

• E.coli– Primary host cell for recombinant protein expression

• Scale-up of culture from shaker flask• Increased aeration

– Potential for higher ODs, and higher protein yields– Potential higher yield of poorly soluble protein

• Low temperature induction of protein expression– Potential higher yield of poorly soluble proteins– Potential higher yield of toxic proteins

• Pichia pastoris– Widely used methylotrophic yeast for protein production

• Above benefits (for E.coli) hold true for P.pastoris

• Algae– Diverse group of microorganisms rich in nutrients,

proteins and active compounds• Scale-up of algae culture to support these biodiversity

profiling activities.• Development of recombinant protein expression

technologies in algae• Ability to grow phototrophically or heterotrophically

• Insect cell culture– Popular recombinant protein expression system

• Baculoviral infection of insect cells (Sf9, Sf21, Hi-5)• Suspension culture• Higher oxygen demand following baculoviral infection

CellMaker REGULAR Applications

E.coli: Scale-up from shaker flasks in the CellMaker

0 45 105 135 180 240 300 3300

0.5

1

1.5

2

2.5

3

OD CellMakerOD Shaker

1mM IPTG

Time (min) OD CellMaker OD Shaker0 0.11 0.09

45 0.22 0.14105 0.61 0.54135 1 0.9180 1.7 1.6240 2.4 2.1300 2.7 2.3330 2.8 2.4 1 2 3

Target Protein

1: Uninduced2: CellMaker3: Shaker

3.5hr induction of protein expression in E.coli at 37°C

Data provided by S Whyte (TwistDX)

Shaker flask, Regular and Plus

P. pastoris : Improved protein yield in the CellMaker

• Enhanced aeration of media through sparge tube

• Oxygen enriched gas supply, maintained at 4L/min Oxygen + 2L/min Air

• Higher ODs obtained compared to shaker flasks

• 1.5-fold increase in biomass

• 2-fold increase protein yield

• Protein appropriately glycosylated and secreted

0 24 48 72 960

10

20

30

40

50

60

Pichia pastoris growth at 29°C

CellMaker RegularShaker

Time (hours)

OD

TIME OD (CellMaker) OD (Shaker)

0 0.94 0.94

24 40 33

48 49 33.8

72 50 32.5

96 54 33

Data provided by M Rossmann (LMB, Cambridge)

S. Aureus Bacteriophage: Scale-up in the CellMaker

0 50 100 150 200 250 3000

0.1

0.2

0.3

0.4

S.aureus OD600

OD 600 (3)

Time (mins)

OD

600

Phage addition

Data kindly provided by Y Jia (Novolytics, University of Warwick)

TIME (mins)

OD600 Comments

30 0.09770 0.16290 0.26995 - 1% phage (80ml) added100 0.350 OD taken straight after

phage addition185 0.358 Sign of cell lysis255 0.046 Culture cleared; harvest

• Seed the CellexusBag with S.aureus

• Allow bacteria to progress to early exponential growth phase

• Inoculate with bacteriophage

• Phage-enriched media later harvested following successful phage infection and lysis

• Convenient, user-friendly, consistent system for scale-up of bacteriophage production

• Growing algae utilises windows in CellMaker Enclosure

• Perspex panels allows light through but insulates CellexusBag

• Peltier heat pumps cool CellexuxBag to 26oC (or as low as 15oC)

Algae: Growth in the CellMaker

3

In collaboration with the Welding Institute, Abingdon, Cambridge

CellexusBagTM - the first Cellexus technology

2

3

1

Key to the effective

mixing by gas (airlift)

and propellers (STR) is

the geometry of the

bioreactor.

2 patent applications filed World-wide

Reflector

Low heat, high efficiency lightsource

CellMaker System Features & Benefits

Features BenefitsSimple 30 minute set-up Saves time, simplifies trainingUnique airlift bags Gentle but effective aeration to improve

yieldsOxygen generator (up to 4L/min) Simple installation

Saves moneyNo oxygen bottles to handle

Peltier-driven cooling & heating Greater application scope (e.g. expression of toxic proteins in E.coli clones) Algae at 26oCInsect cell growth (e.g. at 27oC)

Accurate temperature profile (+/-0.1oC) Reliable processes which give optimal protein production

Efficient condenser Removes vapour and odour from exhaust gases, creates better user environment

Highly robust build quality Maximises uptime 8L & 50L units available Choice of enclosure sizes to suit batch Scalable design Flexible designSimple operator software Fast set up time, simplifies training

June14

Thank you for your attention

Cellexus Ltd, Albacom, George Buckman Drive, Dundee, DD2 3SPinfo@cellexus.com