lonza peptides “the trusted peptides partner, serving your life cycle needs” updated 14 apr 2011

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