Cresset is a computational chemistry company that provides software and consulting services to pharmaceutical and biotech companies. It has over 15 years of experience, 270+ projects delivered globally, and customers in North America, Europe, India, China, Japan and Korea. Cresset's expert computational chemists use ligand-based and structure-based modeling workflows to help customers gain insights into protein-ligand binding and design new molecules. Case studies demonstrate how Cresset has helped discover new hits and develop patents for clients. Testimonials from CEOs and heads of research praise Cresset's knowledge, collaboration, and ability to advance drug discovery projects.

1. Make the Molecules that Matter
Dr Martin Slater, Director of Consulting Services

2. © CressetCONFIDENTIAL
> Founded 2002
> Software
> 15 of 20 top pharmas
> Hundreds of customers across NA, EU, India,
China, Japan, Korea
> Services
> 270+ projects delivered to customers globally
> Support medicinal and computational
chemistry through ligand-based and
structure-based software and services
> Growing and maturing company
> 20% compound annual growth rate since 2010
> 35+ staff on 3 continents
Cresset

3. © CressetCONFIDENTIAL
> Considerable cost savings to be made
> Increase efficiency of, or reduce, lab based FTE requirements
Why outsource computational chemistry?
Chemists
Biologists
Consumables
Equipment
Lab space
£500k - £5,000k per project
Modelers
Software
CPUs
£20k - £100k per project
Just make the molecules that matter?

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Cresset: The science

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Field points
3D Molecular Electrostatic
Interaction Potential (MIP)
N
N
Br
F F
F
SH2N
O
O
Field points
= Shape
= Hydrophobic
MIP contains too much
information to use
computationally in a
reasonable time
Field points provide
computationally
tractable framework for
electrostatic similarity
= Positive
= Negative

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Expert computational chemists
> Computational chemistry
> Medicinal chemistry
> Structural biology
> Informatics
> Europe
> North America
> Japan
> India
> Large pharma
> Biotech
> Agrochemical
> CRO
> Academia
Cross-industry experience and expertise

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Typical activities and workflows
As your science partner we share your goals and challenges

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Need IP for a new protein target X (no ligands): Modeling workflows?
Protein
target X
Known
protein
target Y
Sequence …yes!!
Literature – what is known:
• How does it function?
• X-rays?
• Substrates?
• Ligands?
• SAR?
• Proteins partners
• Mutagenesis
• Chimeras
Intelligence gathering Sequence match - how similar?
• Literature data
• X-rays
• Substrates / proteins partners
• Ligands and SAR
• Ligand binding info
• Mutagenesis
• Chimeras
Homology
model
Hit list of commercial
compounds to procure
and test in biological
screening
Dynamics Loop modeling
Pocket detection Electrostatic Complementarity™
Water modeling FEP
Structure-based virtual screening
Binding
pocket ID
Sequence search

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Gain deep insights into protein-ligand binding

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Need IP for a new protein target X (ligand data): Modeling workflows?
Intelligence gathering
Ligand
superimposition
Hit list of commercial
compounds to procure
and test in biological
screening
SAR analysis
QSAR
Ligand-based virtual screening
Optimization follow-up modeling
New molecules to
synthesize and test
De-novo
design
Fragment
replacement
Protein
target X
Known
protein
target Y
Sequence search
Sequence …yes!!
Literature – what is known:
• How does it function?
• X-rays?
• Substrates?
• Ligands?
• SAR?
• Proteins partners
• Mutagenesis
• Chimeras
Sequence match - how similar?
• Literature data
• X-rays
• Substrates / proteins partners
• Ligands and SAR
• Ligand binding info
• Mutagenesis
• Chimeras
Ligand
binding
hypothesis
3D Bioactive
conformation

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Need IP from phenotypic screen: What are the modeling workflows?
Intelligence gathering
De-novo
design
Fragment
replacement
Ligand
superimposition
SAR analysis
QSAR
Hit list of commercial
compounds to procure
and test in biological
screening
New molecules to
synthesize and test
Sequence …yes!!
Literature – what is known:
• How does it function?
• X-rays?
• Substrates?
• Ligands?
• SAR?
• Proteins partners
• Mutagenesis
• Chimeras
Optimization follow-up modeling
Ligand-based virtual screening
Templating:
3D Bioactive
conformation

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Compare and convert ligands across chemotypes
PDB:2ogz PDB:3g0g
Bioisosteres Bioisosteric
groups

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Need IP for a new protein target X: What are the modeling workflows?
Intelligence gathering
Structure-based virtual screening
De-novo
design
Fragment
replacement
Protein
target X
Known
protein
target Y
Homology
model
Binding
pocket ID
Ligand
binding
hypothesis
Ligand
superimposition
SAR analysis
QSAR
Dynamics Loop modeling
Pocket detection Electrostatic Complementarity™
Water modeling FEP
Ligand-based virtual screening
Optimization follow-up modeling
Hit list of commercial
compounds to procure
and test in biological
screening
New molecules to
synthesize and test
Sequence search
Sequence …yes!!
Literature – what is known:
• How does it function?
• X-rays?
• Substrates?
• Ligands?
• SAR?
• Proteins partners
• Mutagenesis
• Chimeras
Sequence match - how similar?
• Literature data
• X-rays
• Substrates / proteins partners
• Ligands and SAR
• Ligand binding info
• Mutagenesis
• Chimeras
3D Bioactive
conformation

14. © CressetCONFIDENTIAL
Case study: Applying Blaze™ to a natural ligand
N
N
N
N
S
O
O
N
N
N
O
O
O
IC50 470nM
Similar patents later
filed by Incyte
IC50 1100nM
Similar patents by AZ
IC50 170nM
Client patent
O
O
OHHO
O
H
H
H
11β-HSD1
(Cortisone to Cortisol)
Match template across
3,000,000 commercially
available compounds

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Case study: Discovery of Tioxazafen

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Case study: Testing in silico hypotheses in vitro
Biological Sciences - Microbiology:
Jason D. Oliver, Graham E. M. Sibley, Nicola Beckmann, Katharine S.
Dobb, Martin J. Slater, Laura McEntee, Saskia du Pré, Joanne
Livermore, Michael J. Bromley, Nathan P. Wiederhold, William W.
Hope, Anthony J. Kennedy, Derek Law, and Mike Birch
F901318 represents a novel class of antifungal drug that inhibits
dihydroorotate dehydrogenase
PNAS 2016 113 (45) 12809-12814; published ahead of print October 25,
2016, doi:10.1073/pnas.1608304113

17. © CressetCONFIDENTIAL
cressetgroup
martin@cresset-group.com
Questions
Cresset has consistently delivered insightful support to our
drug discovery efforts. In our experience, their knowledge,
responsiveness and collaborative approach have set them
apart from their competitors.
Dr Neil Murray, CEO, Redx Pharma
This is a very important and exciting project for my team so
thank you for your good work. The incredibly high hit rate from
your compound list [Blaze] is intriguing.
Cresset is a valuable partner in our drug discovery programs.
Their deep knowledge of computational chemistry and its
application to drug discovery is enabling us to progress
multiple projects across a wide range of target classes very
quickly and cost-effectively.
Dr Neil Murray, CEO, Redx Pharma
“F2G have used Cresset’s consulting services for over two years. We really
like the powerful combination of excellent software tools and molecular design
expertise which we get from working with Cresset.”
Dr Graham Sibley, Head of Chemistry, F2G
Cresset Discovery Services’ computational experience and
high standard of scientific support is ideally suited to help drive
the next stage of this project.
Dr Richard Boyce, Senior Director of Research, PhoreMost