The GS Gene Expression System™

1
The GS Gene Expression System
2
The GS System is a widely accepted,
industry-leading expression system

• 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
basicresearch
diseasediscovery
drugdiscovery
drugdevelopment
clinicaltrials
production
packaging
marketingsalesdistribution
Lonza Development Services Manufacturing
Customer In-Licensing Lonzas GS Technology
5
Using the GS System is proven to improve yields
and speed
6
Using the GS System leads to higher product
concentrations
Product concentrations for GS-CHO cell lines
making different antibodies in Lonzas 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 Lonzas 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 Alexions Soliris and 3
non-disclosed
10
The GS System and out-licensing team ensures
your needs are meet

• Qingyu Cao
• Licensing and Technology Manager
• 33 3 20 26 8738
• qingyu.cao_at_lonza.com
• General
• 228 Bath Road, Slough SL1 4DX, Great Britain
• 44 1753 777 000
• GSLonza_at_lonza.com
• Online
• www.lonza.com

• Arun NatarajDirector of Licensing Technology
  Sales
• 1 201 316 9485
• arun.nataraj_at_lonza.com
• Isabella SharrattSales Business Development
  Administrator
• 44 1753 716 676
• isabella.sharratt_at_lonza.com

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 Lonzas proprietary media and feeds
• Technical updates Support GSLonza_at_lonza.com

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 users
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