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. Biopharmaceuticals Food additives Cosmetics Biofuels

Worldwide sales dynamics Increasing trend towards use of disposables Cost savings Reduced downtime Reduced risk of contamination

Cost comparisons stainless steel single use -30% Electricity -30% Electricity -38% Space -38% Space -62% Steelwork -62% Steelwork -87% Water -95% Cleaning Material Reference: Sinclair A, et al The environmental impact of disposable technologies. BioPharm International Supplements.

Worldwide sales

Worldwide sales (fermentation)

CellMaker Touchscreen User interface Communications + sensor readers Gas supply + Mixing + temp control Regular Plus Felix 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 Time (min)OD CellMakerOD Shaker Target Protein 1: Uninduced 2: CellMaker 3: 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 TIMEOD (CellMaker)OD (Shaker) Data provided by M Rossmann (LMB, Cambridge)

S. Aureus Bacteriophage: Scale-up in the CellMaker Data kindly provided by Y Jia (Novolytics, University of Warwick) TIME (mins) OD 600 Comments % phage (80ml) added OD taken straight after phage addition Sign of cell lysis 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 26 o C (or as low as 15 o C) Algae: Growth in the CellMaker Reflector Low heat, high efficiency light source

CellMaker System Features & Benefits FeaturesBenefits Simple 30 minute set-upSaves time, simplifies training Unique airlift bagsGentle but effective aeration to improve yields Oxygen generator (up to 4L/min)Simple installation Saves money No oxygen bottles to handle Peltier-driven cooling & heatingGreater application scope (e.g. expression of toxic proteins in E.coli clones) Algae at 26 o C Insect cell growth (e.g. at 27 o C) Accurate temperature profile (+/-0.1 o C)Reliable processes which give optimal protein production Efficient condenserRemoves vapour and odour from exhaust gases, creates better user environment Highly robust build qualityMaximises uptime 8L & 50L units availableChoice of enclosure sizes to suit batch Scalable designFlexible design Simple operator softwareFast set up time, simplifies training

June14 Thank you for your attention Cellexus Ltd, Albacom, George Buckman Drive, Dundee, DD2 3SP