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Lonza Peptides
“The trusted peptides partner, serving your life cycle needs”
Updated 14 Apr 2011
slide 2Apr 19, 2023
Certain matters discussed in this presentation may constitute forward-looking statements. These statements are based on current expectations and estimates of Lonza Group Ltd, although Lonza Group Ltd can give no assurance that these expectations and estimates will be achieved.
The actual results may differ materially in the future from the forward-looking statements included in this presentation due to various factors. Furthermore, Lonza Group Ltd has no obligation to update the statements contained in this presentation.
Note: All slides are incomplete without verbal comments.
Disclaimer
slide 3Apr 19, 2023
Nature: An unlimited source of inspiration!“Predatory marine cone snails use a diverse mixture of peptides known as Conopeptides in the capture of their prey …
Each cone snail may contain up to 200 peptides and given there are over 700 cone snail species, … the library of bioactive peptides using animal venoms is huge.”
slide 4Apr 19, 2023
Nature: An unlimited source of inspiration!
Several peptides extracted from venoms are on the market:
Brand Name Owner Source
Captopril (Capoten) BMS viper venom
Prialt® (Ziconotide) Airmid cone snail venom
Byetta® (Exanatide) Amylin-Eli Lilly lizard venom
Eptifibatide (Integrilin) Millenium/ Schering Plough snake venom
Images FPO, Sources: www. sandesh.com,www.fotopedia.com,www.bangkokpost.com.
slide 5Apr 19, 2023
Agenda
The Challenges of Custom cGMP Peptides Manufacturing
Customer Value Proposition
Lonza, The Right Peptides Partner
slide 6Apr 19, 2023
Increasing Molecular Weight (MW)
Chemical Molecule
Aspirin
(180 Da)
Peptide
6mer
(804 Da)
Antibody
Immunoglobulin G
(150,000 Da)
Protein
Lysozyme
(14,700 Da)
Complexity by Molecular Weight
Cell / Tissue
Surface of an Animal Cell
slide 7Apr 19, 2023
Process development know-how is the key to future success
Right route selection from the beginning based on large-scale experience
Robust process development
Process validation
Process optimization
slide 8Apr 19, 2023
On average, producing 1 kg (net) of peptide generates over 5 metric tons of solvent.
Capabilities and infrastructure are critical to success
Required Infrastructure Strategic (worldwide) sourcing Raw materials in rail-tank-
cars Tank-farms No open handling Adequate warehousing Solvent recylcing systems Exhaust gas treatment Waste Disposal
slide 9Apr 19, 2023
Quality
Impurity Profile
Purity
Scalable Process
GMP
slide 10Apr 19, 2023
HAPI Peptides
Matt- please add challengesAHSK* OEL
(Occupational Exposure Limit)ADI
(Acceptable Daily Intake)
1 > 1mg/m3 > 10mg/d
2 0.1-1 mg/m3 1-10 mg/d
3 0.01-0.1 mg/m3 0.1-1 mg/d
4 0.1-10 µg/m3 1-100 μg/d
5 1-100 ng/m3 0.1-1 μg/d
6 < 1 ng/m3 < 10 ng/d
* Lonza Occupational hygienic substance category
Generic peptides like LHRH family are HAPIs, AHSK 5 (gosereline, decapeptil, leuprolide, busereline, desloreline, triptorelin…)
Abarelix, degarelix are also AHSK 5 Avoid cross contamination AND protect the people Low cleaning limit
slide 11Apr 19, 2023
Conjugate Peptides
Lipid
Antibody
SugarCPP
PEG
PEPTIDE
Peptides are versatile platforms for product design
slide 12Apr 19, 2023
Pre-clinical ToxicologyCommercial
Phase I Phase II Phase III
Purity
95% 96-97% >98.0%
European
Pharmacopeia 6.5
Purity challenges based on new regulation in 2010
slide 13Apr 19, 2023
FDA
New regulation will challenge peptide process development
Stage 1: Process Design Stage 2: Process Qualification Stage 3: Continued Process
Verification
Phase 0+1 Phase 2 Phase 3Launch / Production
Generic
Process Life-cycle
slide 14Apr 19, 2023
Agenda
The Challenges of Custom cGMP Peptides Manufacturing
Customer Value Proposition
Lonza, The Right Peptides Partner
slide 15Apr 19, 2023
Global, Integrated, Strategic Supply Chain
Broad network of suppliers
Negotiation power
Regular suppliers audit
Security of starting materials supply (Group synergies, back integration for raw materials)
slide 16Apr 19, 2023
Large-Scale Manufacturing Expertise
Multi-100 kgs of peptide API production yearly
Large purification HPLC capacity (up to 60 cm)
3 Technologies (SPPS, HPPS,Recombinant DNA)
4 Sites (Belgium, Switzerland, Czech Republic, China)
slide 17Apr 19, 2023
Benefit from Lonza synergiesduring your peptide API development
Peptides Conjugates
Large-scale peptides for non-pharma applications (cosmetic, nutrition, detergent, surfaces treatment …)
Highly potent peptides
2nd generation process for large-scale peptide manufacturing via recombinant technologies
slide 18Apr 19, 2023
Quality by Design at Lonza
The definition
A true answer to FDA expectations
A maximally efficient, agile, flexible pharmaceutical manufacturing sector that reliably produces high quality drug products with less extensive regulatory oversight
Build quality in the process
Based on sound science and knowledge
Proactive to problems
Control strategy based on risk assessment
Continuous improvement and process verification
slide 19Apr 19, 2023
Quality by design A Tailored Approach in Process R&D
Process DesignProcess
Qualification
Continued Process
Verification
Phase 0+1
The roadmap to process validation
process selection
critical attributes
risk assessment
design space
control strategy
continuous improvement
Kn
ow
led
ge
Phase 2 Phase 3Launch / Production
Generic
Process Life-cycle
slide 20Apr 19, 2023
Full Regulatory Support
DMF
CMC section
Audit
Inspection track records
Corporate experience
Accreditation from Japanese authorities
slide 21Apr 19, 2023
Modeling of Peptide PurificationsStudy of Peptide Aggregation
Collaboration / thesis Centrifugal Partition Chromatography (CPC)Collaboration / Thesis
Nanofiltration and Molecular ImprintingEU Program
SPPS and MethodologyConsulting and Route scoutingContinuous process
Thesis
Technology Development through R&D Outsourcing
Trade secret Automatic Peptide Synthesizer
Collaboration
slide 22Apr 19, 2023
Easy, Effective, Regular Communication
Customer-dedicated Data
SharePoint
In-house Video Conference Tools
Worldwide Sales
Presence
SteeringCommittee
Peptide Specialists
QA
Operations
PMCustomer
Legal
We bring everyone to the table
slide 23Apr 19, 2023
Time Savings
We serve all your life cycle needs
Full In-house
Capabilities30 Years of Peptide
R&D expertise
Large-Scale
Manufacturing
Know-How
slide 24Apr 19, 2023
Costs Savings
Route selection, scale-up capabilities and
expertise (low-risk of tech. transfer) based on
long-term customer forecasts
Swiss Tax Structure: Lonza to collaborate to establish tax holiday
opportunities for commercial deliveries
Lonza Nansha platform for ISO
needs
Strong expertise in process scale-up
and cost improvement
slide 25Apr 19, 2023
Nansha, ChinaSmall scale (100mg - 10g non-GMP)10 peptide chemists
Braine, Belgium
Large scale (solid and solution phase)50+ chemists/technicians
Visp, Switzerland
Large scale (solid and solution phase)
USP + dedicated DSP20+ chemists/technicians
Multi-Site Multi-TechnologiesFinancially Sound Backward Integrated
Peptides
Security of Supplyfor Chemical Processes
slide 26Apr 19, 2023
Flexibility
Experienced Project
Management Team
Unique Awareness of Peptide Challenges
Custom Synthesis Mindset
Multi-Site
Four Shift Systems
slide 27Apr 19, 2023
You will benefit from IP protection
Product Life Cycle Management meeting, including Lonza patent support
Transparency on Lonza IP strategy with our key customers to better protect their products from their competitors
We aim to protect a customer’s product during its life cycle
Access to Lonza patents portfolio
slide 28Apr 19, 2023
Agenda
The Challenges of Custom cGMP Peptides Manufacturing
Customer Value Proposition
Lonza, The Right Peptides Partner
slide 29Apr 19, 2023
Choose Lonza for: R&D
Quality by Design Specific R&D know-how to improve your processes 30 years of experience and successful track record R&D peptide teams in Visp, Braine, Nansha
slide 30Apr 19, 2023
Your small-scale samples platform
milligram-scale gram-scale
Early stage non-GMP services to serve every step of your product life cycle
Specific knowhow, fast and low-cost efficient development
Dedicated peptide staff IP protection
From mg to grams, Lonza has your small-scale platform
Preferred Collaboration with California Peptide
Lonza, China
slide 31Apr 19, 2023
O
NH
NH
ONH2
NH
NHO
NH
ONH
NH
O
OOH
NH
O
NH
O
O
OH
NH
O
NH2
NH
O
NH
NH
O
NH
O
OH
NH
O
NH O
NH
O
NH O
O
NH2
NH
O
NH
OO
OH
NH
OO
OH
NH
ONH2 NH
O ONH2
NH
OO
NH2
NH
O
OH
NH
O
OH
NH
O
OH
NH
O
NH
O
NH
O
NHN
NH
O
OH
NH
O
NHO
NH
O
O OH
NH
O
O OH
NH
O
OH
NH
O
O NH2
NH
O
O
NH2
NH
O NH2
O
OHO
O
NH2
O
Fuzeon® (T-20 Roche)
Case Study: Successful Route Selection
Source: 2004 Trimeris - NP2D event Zermatt, Switzerland
slide 32Apr 19, 2023
Case Study: Quality by Design (QbD)
NH
NH
O
NH
NH3
+NH
NH
O
NH
NH
O
OHNH
O
O
NH
O
N
NH
NH
O
O
NH
O
CH3
O
O
Bremelanotides ® (PT-141, Palatin Tech.)
slide 33Apr 19, 2023
Case Study: Quality by Design (QbD)
Catalyst Pd(Ph3)4
Pd(OAc)2 / P(oTol)3
PdCl2(Ph3)4
Scavengers / proton donor HCOOH/DIEA Dimedone Morpholine AcOH/NMM Phenylsilane Me2NH.BH3 (DMAB)
80.00 85.00 90.00 95.00 100.00
140.00
142.50
145.00
147.50
150.00yield Contour
79
80
80
81
81
82
82
83
83
83
84
85
86
87
88
88.5
666666
Design Space
Factor Screening DoE
Optimization DoE
Solution to selective Allyl/Aloc cleavage
slide 34Apr 19, 2023
Case Study: Synergies lead to Innovation
Recombinant E. coli(carboxy terminal fragment) H-Arg-Pro-Gly-Gly-Gly-Gly-Asn-Gly-Asp-
Phe-Glu-Glu-Ile-Pro-Glu-Glu-Tyr-Leu-OH
=
Semisynthesis of Bivalirudin®
Inhibition of Thrombin Therapeutic value in angioplasty after acute myocardial infarction
API (Bivalirudin®)
+Chemical Synthesis (amino terminal fragment)
BOC-D-Phe-Pro-OSu
fragment condensationdeprotection
final purification
slide 35Apr 19, 2023
Successful Regulatory Inspections History: Lonza Braine, Belgium
Who When What Remarks
FDA 2001 Pre-approval inspection UCB Bioproducts Braine-l‘Alleud
FDA 2003 Follow up Inspection UCB Bioproducts Braine-l‘Alleud
FDA 2005 Pre-approval inspection Approval by 12 march 2006
FDA June 2009 Successful GMP systems and pre-approval inspection
FDA February 2011 Pre-approval inspection BI, Nansha
Korean FDA November 2007 Pre-approval inspection Approval, June 2008
EU Regulatories December 2008 GMP inspection Successful GMP inspection
slide 36Apr 19, 2023
Lonza’s Visp & Nansha facilities have a long history of successful inspections
slide 37Apr 19, 2023
Let’s Share Our PeptidesFuture Together!
© Wolfgang Staudt
Peptides Excellence
Customer Service
Road to Success
Experienced Teams
Thank You