Translating innovative biology
into bioactive moleculesAbout usYour value creator in early discovery• Science-driven customized projects from target identification to Hit-to-Lead• Over 130 scientists covering different areas of expertise to promote High Quality LeadFinding• Operational sites:• Milan (Italy) - HQ
• Naples (Italy)• Business Offices:• Boston (USA)• Copenhagen (Denmark)• Basel (Switzerland)• Founded in 2001
• Business segment: pharma, biotech, agrochemical, flavor & fragrance, food & beverages

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Integrated drug discovery at Axxam

In Vitro Assays● Assay development
o Cell-based assays
o Cell-free assays● Ready-to-use assays● Client assay transfer & optimization

Biological Platforms● iPSC platform● Optogenetics● Organellar electrophysiology● RNA biology

3Axxam Company Overview - Copyright 2024 © Axxam S.p.A.

High-ThroughputScreening● Versatile automation platforms● All optical readout modalities
o Fluorescence, luminescence,
TR-FRET (HTRF), etc.
● High-throughput patch clamp● High content screening● Quantitative gene expression screening

Compound Libraries& Management● Axxam compound libraries
o AXXDiversity
o Symegoldo RNA targeting libraryo Natural products● Client library management & storage● Library reformatting (384 & 1536 MTP)

Hit-to-Lead● Compound profiling● Analytical chemistry● In vitro DMPK assays● Phys-chem profiling● Medicinal chemistry

Cell-based assay development• Functional and phenotypic assays for HTS and compound profiling / hit-to-lead

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Axxam Company Overview - Copyright 2024 © Axxam S.p.A.

Cell-based assay development• Functional and phenotypic assays for HTS and compound profiling / hit-to-lead• Different cell models✓ recombinant cell lines✓ insect cells✓ tissue specific cells✓ iPSC-derived✓ primary cells✓ genome-edited✓ inducible systems✓ 3D cultures
Neurons (rat DRG cells) and neurites stained with β-III Tubulin(Green LUT) in co-culture with glial cells (Pink LUT).
20X Magnification

5Axxam Company Overview - Copyright 2024 © Axxam S.p.A.

Cell-based assay development• Functional and phenotypic assays for HTS and compound profiling / hit-to-lead• Different read-outs✓ Opticalo Luminescence – NanoBit – HiBito Fluorescenceo TR-FRET – BRET -Alphascreen/Alphalisa✓ Electrophysiology✓ Imaged-based / Phenotypic✓ Gene expression (TaqMan)• Innovative technologies and tools:✓ Genome editing (CRISPR-Cas9)✓ Optogenetics genetically encoded indicators: GCaMP, pH sensors, SuperClomeleon,YFP, voltage sensors, cAMP sensors
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Cell-free assay development• Functional assays for HTS and compound profiling / hit-to-lead• Expression systems: E. coli, insect cells, mammalian cells• State of the art protein production and purification platforms

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Cell-free assay development• Functional assays for HTS and compound profiling / hit-to-lead• Homomultimeric and heteromultimeric targets• Integral transmembrane enzymes• Main applications:✓ Enzymatic✓ Interaction assays: Protein-Protein, Protein-DNA,Protein-RNA✓ Biophysical assays (e.g., Therma Shift Assay-TSA)• Readouts:✓ Luminescence✓ Fluorescence - FP
✓ TR-FRET, BRET, AlphaScreen/Alphalisa✓ Absorbance
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Biological platforms• Axxam expertise meets cutting-edge techniques
Organellar ElectrophysiologyiPSC✓ Manual patch clamp on isolated✓ Several cell models (neurons; glia;

organelles: LysoPatch; MitoPatch;
NucleoPatch✓ Unique Mode of Action studies✓ Automated LysoPatchcardiomyocytes; hepatocytes; etc.)✓ Gene editing & reporter cell line

generation✓ Functional studies (aggregation assays;

cytokine release; cytotoxicity, etc.)

OptogeneticsRNA platform✓ Light actuators/ sensor-based cell assays✓ Splicing assays✓ FLIOP – Fluorescence Imaging & Optical✓ siRNA/shRNA/ASO screeningsPacing

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✓ Gene expression-based analysis

High-throughput Screening (HTS)• 384 and 1536 MTP• Fully Automated robotic systems• Biochemical and Cell-based• Plate optical detection✓ Luminescence (flash, glow, NanoBit, Hibit, AlphaScreen)✓ Fluorescence (FI, FP, TR-FRET (HTRF))✓ Absorbance• Integrated readers:✓ Hamamatsu✓ PHERAStar✓ FLIPRTETRA & PENTA ✓ Envision
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Axxam Company Overview - Copyright 2024 © Axxam S.p.A.

High-throughput Screening (HTS)• Electrophysiology✓ SyncroPatch 384i (Nanion)✓ QPatch II 48X (Sophion)• High Content Screening✓ Cell painting approach✓ Opera Phoenix (PerkinElmer)✓ Operetta (PerkinElmer)• TaqMan screening/Gene expression✓ Fully Automated robotic system fittedwith 2 QuantStudio✓ Multiplexing - more genes can beeasily investigated
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Axxam Company Overview - Copyright 2024 © Axxam S.p.A.

Compound Libraries
AXXDiversity

Symegold✓ ~ 349.000 small molecules✓ ~75.000 small molecules✓ Driven by quality and✓ Specialised chemistrydiversity✓ Five different nonoverlapping subsets✓ High novelty

RNA-targeting library

NatPure✓ ~ 2.000 small molecules✓ ~13.500 purified natural compounds✓ Suitable for finding splicing & RNA-✓ Mainly derived from plants andprotein interaction modulators✓ Driven by quality and diversity✓

12✓ Driven by quality and diversity

High novelty

Axxam Company Overview - Copyright 2024 © Axxam S.p.A.

microbes✓ High diversity

Compound Libraries: AXXDiversity• ~ 349.000 small molecules• Driven by quality and diversity, not target class focused• Five different non-overlapping sets available
Discovery set

ExplorerPLUS set

180.000 molecules, with amean of 15 analogues per
chemotype.
ProvidesSAR
information

98.000 molecules. Highest
coverage of diversity. Ideal for
novel peripheral and centraltargets

Probe set
12.000 decorated fragment-likemolecules, characterized bylower MW. Ideal starting point
for structure-enabled programs

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ExplorerFAST set
24.000 molecules, with a highdegree of chemical tractability
for fast hit expansion

ExplorerCNS set
35.000 molecules, characterizedby optimized MPO scores andspecifically biased for CNS, pain
and intracellular targets

Compound Libraries: Symegold• ~ 75.000 small molecules• High novelty, lead/drug-likeness• High diversity• Specialised chemistry, unlike commercially available catalogue compounds• Available thanks to Axxam partnership with Symeres• Symeres expertise for rapid hit expansion and optimisation• No structures in common with AXXDiversity in terms of molecule identity

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Axxam Company Overview - Copyright 2024 © Axxam S.p.A.

Compound Libraries: RNA-targeting library• ~ 2.000 small molecules• Suitable for finding splicing & RNA-protein
interaction modulators• Lead/drug-likeness• High novelty and chemical diversity• Average purity: > 95%• Optimal starting point for Med Chem programs

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Axxam Company Overview - Copyright 2024 © Axxam S.p.A.

Compound Libraries: NatPure• ~ 13.500 distinct pure naturalcompounds in screenable format• Mainly derived from plants and microbes• ~ 30% are novel compounds• Purified and fully analytically characterized, including elucidation of their chemicalstructures• High chemical diversity guaranteed by preselection of biological sources• Contains around 4.900 distinct chemical clusters

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Axxam Company Overview - Copyright 2024 © Axxam S.p.A.

HTSPLUS: Unlock the True Value of Hits
Target ID &validation

Assaydevelopment

Hit
identification

Lead
optimization

Hit-to-Lead

PLUS

Assay
transferAssayadaptation toautomation

Pilot
screening

Primaryscreening

PLUS
HTS
Integrated hit qualification allows datadriven hit selection and facilitatessubsequent hit-to-lead optimization

Hitconfirmation

Activity
determination

Hit
validation

Validated Hits
▪ Validated activity▪ Validated specificity▪ Elucidated structures▪ Purity check▪ In vitro ADME

Hit
qualification

Qualified Hits *▪ Hit Target Potency▪ Hit Target Selectivity▪ Hit Target in vitro ADME
▪ Validated chemistry with
Preliminary SAR▪ IP – first assessment(*) Exact Target Profiles (TP) are defined in collaboration with the client

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HTSPLUS - Integrated hit qualification❑ Comm. analog search❑ Struct/Ligand based DD❑ Design of analogs❑ Preliminary SARCADDChemistry❑ Re-synthesis of hits
❑ Synthesis of analogs❑ Chemical tractability❑ IP position

PLUS❑ Phys-chem profile❑ Preliminary ADME

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Select the right hit& progress faster

Hit
qualification

Hit
validation

ADME

Axxam Company Overview - Copyright 2024 © Axxam S.p.A.

Biology❑ Potency &Selectivity❑ Specificity❑ MoA

DiscoveryMAXX - Start right, progress fast
PLUS

In vitro
assaysHit
validation

Hit
qualification

Validated Hits
▪ Validated activity▪ Validated specificity▪ Elucidated structures▪ Purity check▪ In vitro ADMEMAXXDiscovery
Seamless transitions from assay
development to Lead Candidate

Qualified Hits (*)▪ Hit Target Potency▪ Hit Target Selectivity▪ Hit Target in vitro
ADME▪ Validated chemistrywith Preliminary SAR▪ Exploratory IP▪ Computational
chemistry support

MAXX

Hit-to-lead

Lead Candidate (*)▪ Lead Target in vitro ADME
▪ Lead Target Potency & Selectivity▪ Activity in 2° assays▪ Chemical tractability▪ Exploratory IP▪ Feasible PK opt.
▪ Computational chemistry support(*) Exact Target Profiles (TP) are defined in collaboration with the client

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Axxam Company Overview - Copyright 2024 © Axxam S.p.A.

Hit-to-lead: fast and efficient design-make-test cycles

DesignData Science
Data Storage

MedChemConsultancy
Project
Management

ADME

Delivering on pre-defined product target profile
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Axxam Company Overview - Copyright 2024 © Axxam S.p.A.

Chemistry

Biology

Analytics
CompoundLogistics

Multidisciplinary expertise across each project

Molecular Biology

Biochemistry

Cell Factory

Cell Biology

Electrophysiology

High Content Screening• Construct generation• Cell-free assay development• Cell culture• Cell-based assay development• Automated patch-clamp• High content assay development• Genome editing• Enzymatic & molecular interaction • Primary cell lines• Off-the-shelf assays• Manual patch-clamp• Phenotypic screening• RNA biology platforms• Biophysical methods (TSA)• Optogenetics readout• Organellar patch-clamp• Cell Painting

iPS Cells

High-Throughput Screening

Compound Profiling

Compound Management

Data Sciences

Analytical Services & MedChem• iPSC differentiation• Optical, ephys, imaging, gene

• Cell-based; cell-free• Storage and maintenance• HTS Data Analysis• Small molecule quality check• SAR campaign• Compound plate reformatting• Chemoinformatic analysis• Hit qualification• Consultancy• Med-Chem Consultancy• iPSC-derived cell assay dev.
• Compound screening

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expression readouts• Compound libraries

Axxam Company Overview - Copyright 2024 © Axxam S.p.A.

Axxam’s alliance network
A consortium of excellence centers to offer a platform of fully
integrated drug discovery services
Seamless process and coordination throughout the entire
discovery project

Advancing hit discovery
programs with
best-in-class collaborators✓ Mass-spectrometry screenings✓ Proteomics✓ Medicinal chemistry✓ In vivo and in vitro ADME
✓ Customized synthesis✓ Membrane protein expertise✓ Biophysical methods✓ Structural biology✓ Human iPSC-derived cells✓ Reagent kit provider✓ Rodent primary cells

22Axxam Company Overview - Copyright 2024 © Axxam S.p.A.

Why choose Axxam
for early discovery:
World-class expertise in assay development and hit
identification based on our strength in biology and invitro pharmacology
Delivery on challenging projects with an issue-resolving
mindset and can-do attitude

Early discovery under the umbrella of good research
practices (quality management system)
Integrated hit-to-lead project delivery with the goal ofincreasing the probability of successDedicated and professional
team:
Clear project governance with a focus oncommunication quality
Dedicated project team supported by a project manager
and a project leader
Highly qualified and stable workforce
Flexible and adaptable
Long-term and returning clients

Business models:Fee for service

FTE-based and milestone-based contracts
Intellectual property rights: it’s all yours …

Contacts
Francesca Dejure

www.axxam.com

Manager, Business Development
email: francesca.dejure.fd@axxam.com

info@axxam.com

Corporate Offices & Laboratories
Headquarters & Laboratories

Business Offices

OpenZone Campus
Via Meucci 3
20091 Bresso (Milan) / Italy

Cambridge Innovation Center
1 Broadway, Cambridge, MA 02142 / USA

Laboratories

Copenhagen Bio Science Park - COBIS A/S
Ole Maaløes Vej 3, 2200 Copenhagen / Denmark

Novartis Campus
Via Provinciale Schito 131
80058 Torre Annunziata (Naples) / Italy

Switzerland Innovation Park Basel Area AG
Hegenheimermattweg 167A,4123 Allschwil / Switzerland