1. The GS Gene Expression System™

2. The GS System™ is a widely accepted, industry-leading expression system
Owned and licensed by Lonza
A mammalian gene expression system
For therapeutic proteins and monoclonal antibodies
GS-CHO and GS-NS0 cell lines
Widely Accepted
Over 110 companies, 75 academic institutions
Over 95 products in the clinic
100s of high-yielding cell lines created (last 15 years)

3. Principles of the Glutamine Synthetase (GS) System
ATP
ADP + Pi
NH4+ + glutamate
glutamine
methionine sulphoximine (MSX)
MSX = a glutamate analogue that binds to GS irreversibly

4. The GS Gene Expression System™ is accessible at all stages of production
Discovery
Development
Manufacture
Distribution
basic research
disease discovery
drug discovery
drug development
clinical trials
production
packaging
marketing sales distribution
Lonza Development Services & Manufacturing
GS vector & cell line construction
cGMP cell banking
process development & scale up
cGMP production
regulatory support
Customer In-Licensing Lonza’s GS Technology
GS vector & cell line construction
cGMP cell banking
process development & scale up
cGMP production
regulatory support

5. Using the GS System™ is proven to improve yields and speed
High-yielding cell lines
Up to 9.6 g/L GS-CHO 1.9g/L GS-NS0 in chemically defined, animal component-free medium
Speed
No need for rounds of gene amplification
Scale Up
Predictable (1 to 20,000L currently)
Regulatory Acceptance
10 licensed products: Zenapax® (Roche), Synagis® (MedImmune), Soliris® (Alexion), & 5 mAbs, 2 protein
Ease of use
Complete support package

6. Using the GS System™ leads to higher product concentrations
Product concentrations for GS-CHO cell lines making different antibodies in Lonza’s cGMP manufacturing bioreactors
Product Concentration (g/L)

7. The majority of products will achieve more then 2g/L using the GS System™
Product concentrations for GS-CHO cell lines making different antibodies in Lonza’s cGMP manufacturing bioreactors
Number of Cell Lines (Each Making a Different Product)
Product Concentration (g/L)

8. Increasing productivity with the GS System™ lowers relative cost
Assumptions
Product Requirement: 35kg/yr
65% yield across purification

9. The GS System™ is used for a number of well-known commercial products
Zenapax™
Roche - humanized antibody
Treatment of prophylaxis of acute organ rejection in kidney transplant rejection patients
Synagis™
MedImmune - humanized antibody
Prevention of serious lower tract disease caused by RSV (Respiratory Syncytial Virus)
4 additional mAbs: Alexion’s Soliris® and 3 non-disclosed

10. The GS System™ and out-licensing team ensures your needs are meet
Arun Nataraj Director of Licensing & Technology Sales
Isabella Sharratt Sales & Business Development Administrator
Qingyu Cao
Licensing and Technology Manager
General
228 Bath Road, Slough SL1 4DX, Great Britain
Online

11. The GS out-licensing package provides timely, comprehensive support
Patents
Materials
Standard 0.4 series GS vectors
Host cell lines from cGMP cell banks
NSO
CHOK1SV
Transfection Medium System

12. Our GS out-licensing package offers access to years of specific know-how
GS manuals: methodologies, equipment
Vector sequences
Regulatory support
Vector information
Characterization and testing status of host cell banks
Support for media and feeds in regulatory submissions
Working with Lonza’s proprietary media and feeds
Technical updates; Support:

13. GS System Optional Packages / Updates and Improvements
2011: GS-CHO Chemically Defined Animal Component Free (CDACF) Live Version 8 Media System
2011: Light Path™ Discovery Material Supply
2011: Epibase™ Server for Immunogenicity Risk Mitigation
2010: Genetic Characterisation Service
2010: pConPlus vectors
2010: Potelligent® CHOK1SV Cell Line Technology
2007: GS-NS0 and GS-CHOK1 Host Cell Protein ELISA assay reagents and know-how
2006: GS-NS0 and GS-CHOK1SV Host Cell Protein Western Blotting assay reagents and know-how

14. Lonza also offers the GS System™ to customers for research purposes
Research Evaluation Agreement (REA)
Commerical Customers
any product – research use only
Annual fee: £35K

15. The GS System™ license is designed with a user’s needs in mind
Per Product
Required before start of clinical trials for therapeutics
Commercial terms linked to manufacturing source
3rd Party manufacturing (CMO)
£300k per annum and 2% royalties on net sales
Customer or Strategic Partner manufacturing
£75k per annum due from Phase 2, 1.5% royalties on net sales
Lonza manufacturing
License fees waived, 1.5% royalties on net sales
Term
Royalties to patent expiry then 50% reduction to cover know-how.
Multi-product Licenses for using GS as a platform technology

16. The GS System™ has been adopted for licensed therapeutics at every stage
Notes
Total active licensed products: over 240
Total in active human trials / pre-registration: 100
Total approved: 9