2. The Key Organics
Advantage
During the last 28 years, Key Organics has created value for its
customers through its intellectual and hands-on scientific input
which have accelerated their drug discovery projects into clinical
development and product launch.
Through our creative input, we continue to add inventive and patentable
intellectual property as well as developing new chemistries on a wide
range of intellectually and scientifically demanding projects that we
typically deliver to tight deadlines. Our staff have backgrounds from major
pharmaceutical, biotechnology and CRO/CMO’s that include AstraZeneca,
Pfizer, Evotec, Chiroscience, BTG and Novartis.
Our highly flexible business model comprises of FTE and custom chemistry which is carried
out under strict confidentiality. We operate a highly transparent and effective FTE project
management and communications programme that provides our customers with direct access
to project plans and data through our Accelrys Notebook, a Cloud-based e-notebook system.
Hit
Identification
DISCOVERY SERVICES EARLY DEVELOPMENT
Hit-to-lead
Lead
Optimization
Candidate
Selection
Pre-
Clinical
API
Supply
Key Organics Facts:
Who are we?
A UK-based CRO with over 28 years
expertise in synthetic organic chemistry.
Part of the Tennant Group of companies
(founded c. 1700) with >1,000
employees worldwide.
Our customers:
We work for a diverse range of
international life-science companies,
from pharmaceutical and biotechnology
firms to academic laboratories and new
start-up’s.
Our Services:
We offer a wide-range of integrated
bespoke chemistry solutions, from the
custom synthesis of a single compound
to multiple, long-term FTE programmes.
Flexibility:
We work in a close and flexible structure
with our customers as project milestones
often change and resources need to be
re-deployed.
Why work with us?
With established library design
capabilities, an extensive BIONET
product portfolio and a proven track
record in synthetic organic chemistry,
Key Organics is able to fully support
your drug discovery and development
chemistry needs. Our project managers
and scientists are highly experienced
at managing complexity and we
utilise Accelrys Notebook to facilitate
information exchange during our
FTE programmes.
We have worked on thousands
of demanding projects for many
of the world’s leading Life Science
companies from hit identification
to pre-clinical development,
successfully delivering value
through our innovative approach,
creativity and product supply.
Delivering Drug Discovery,
Lead Optimisation and Candidate
Development Support Services
Key Organics has experience in the following phases of
drug discovery and development:
• Hit Identification, fragments, library synthesis,
• Hit to Lead
• Lead Optimisation
• IP exemplification
• Isotope-labelled synthesis
• Route scouting
• Early Process Research & Development
• Delivery of pre clinical batches
• Process Related Impurity (PRI) Identification & Quantification
3. Hit identification, Computational Chemistry & Library Design
Key Organics provides a range of established strategies to deliver high-quality and validated hit compounds. With
substantial pharmaceutical industry experience and a highly experienced team of research scientists, we have
undertaken many successful hit-identification projects to produce synthetically-tractable hit series which have
advanced into the hit-to-lead phase.
We have drug discovery and development experience with small and large molecules (e.g. peptides) across a broad
range of therapeutic areas and biological drug-target classes.
Through our collaboration with Prosarix Limited, we offer a unique
computational library generation service, . These ‘ready to
run’ virtual libraries are combined with fast follow-on synthesis, and offer
a number of advantageous features:
• Novel and large drug-like chemistry space designed to a specific
target family (e.g. Kinases and SP1R)
• Library design based on in-house BIONET reagents and templates
which enables rapid synthesis
• Virtual screen of library aligned against Customers target
pharmacology profile
• Design and synthesis of compounds delivered
• Provides unique service capability for target class -
bespoke design and chemistry
KeyFinder Process
Novel chemotypes
for target class
Client target
selection
Library designs
Library screen
Ready to screen...
Virtual library
construction
Synthetic
candidate selection
Synthesis and
delivery
Testing
In-house reagents
Hit-to-Lead
We have undertaken numerous
projects involving the design
and synthesis of novel
molecules, either singletons
or using our parallel chemistry
techniques to prepare focused
arrays (typically up 10 to 50
compounds at 1 - 50mg scale)
with chemical purities of
≥95% (by LC-MS and NMR) for
in vitro screening and ADME
profiling.
Lead Optimization
We have extensive experience of collaborative R&D where we are able to move customer projects forward
through the milestones of Lead Optimisation. We add value through the analysis of data and providing
rationale suggestions on future targets using computational tools such as Data Warrior which is further
supported by our expertise in synthesis – driven target selection. Our approach is focused on enhancing
potency, improved physico-chemical properties, metabolic profile and building a strong IP position. Our
project management structure is highly flexible and we are able to respond rapidly to project changes.
This approach, coupled with a high level of productivity, enables a robust and efficient design/make/test
cycle to be established and maximises the use of resources.
In later Lead Optimisation, our team are highly experienced in the synthesis and investigation of more
challenging chemistry as the SAR is better understood and the need for more “bespoke” compounds
becomes clearer as well as establishing early route improvements for pre candidate compound
batches. We also have in depth experience of the synthesis of project support compounds such as
deuterium and 13
C labels for PK/PD studies and synthesis of competitor compounds to assist in profiling
and benchmarking.
Early PR&D Pre-clinical Candidate Delivery
Key Organics has supported many drug discovery programmes, from hit validation to preclinical studies. We have particular expertise in
the scale-up of synthetic routes to prepare multi-gram quantities of a lead compound for further studies. As many of our customers work
to tight deadlines, we seek to optimise the efficiency of a scale-up route, in terms of time and material costs, by reducing the number of
steps and finding alternatives to chromatographic purification. Our synthetic chemists work closely with our in-house analytical team to
ensure that final compounds meet or exceed the purity specification required by the customer.
The approach facilitates the generation of
novel lead candidates and associated new IP.
4. Isotope-labelledSynthesis
Through our Custom Synthesis programme,
we can provide deuterium and/or 13
C labeled
API’s, intermediates or metabolites.
One, non confidential, example was the recent
synthesis of the dual labeled form of Algoliptin,
the orally administered anti-diabetic drug in
the DPP-4 inhibitor class, originally developed
by Syrrx.
Through an established partnership, we can
also offer hot labeled API’s, also produced
under GMP conditions if required.
Synthetic Chemistry
Our team of highly experienced chemists have acquired extensive synthetic organic
chemistry capabilities and expertise that cover the following areas:
• Multi-step complex custom synthesis
• Asymmetric synthesis
• Heterocyclic chemistry
• Synthesis of literature standards
• Cold labelled compounds
• Pro-drug synthesis
• Manufacturing impurities and metabolites
• High pressure reactions (100mL – 4L autoclaves)
• Hydrogenations
• Carbonylations
• High temperature ammonia reactions
Unique, Proprietary Fragment Libraries
Key Organics has designed and synthesized several unique, proprietary
fragment libraries that includes; CNS, Premium Fragments
and a Fluorine set. Our new “2nd generation BIONET Premium
Fragment Library” (to be launched in Q1 2015) has been developed in close
collaboration with The Broad Institute (Cambridge MA, USA) and NMX Research
and Solutions (Montreal, Canada) according to the following design criteria:
• Rule of 3 compliant: MW ≤300, cLogP ≤ 3, number of HBA/HBD ≤ 3, PSA ≤ 60 and Number rotatable bonds ≤3
• Heavy atom count (HAC) ≤ 16
• Does not include substructures identified as promiscuous or reactive by empirically determined rules
(BMS, PAINS, Kazius and Bursi toxicophores, Lilly Med Chem Rules)
• Inclusion of diverse scaffolds that are present in bioactive compounds and that have 3-dimensionality
• Clustering and Diversity analysis
• Passes chemist visual inspection
• Solubility at 1mM in PBS buffer and signs of aggregation determined by 1
H NMR spectra
“Selection by scaffolds” is a powerful way of selecting molecules to yield synthesizable and recognizable structures.
The goal of selection will be to find fragment-like molecules with diverse scaffolds that are present in bioactive
compounds and that have 3-dimensionality. This unique library also maintains good diversity in functional groups.
13
CD3
-Alogliptin
N
N
NH2
N
O
O
D
13
C
D
D
N
5. How We Make a Difference
Transparent, Efficient & Honest Communication
For all FTE projects, we utilise the Accelrys Notebook, a Cloud-based e-notebook system that is both reliable and
secure. Customer project plans and experimental data can be readily accessed 24/7 through a free user-license. This
software and data transparency complements our communications approach that includes weekly or daily project-
update meetings as well as written reports as required by the client.
Access to our Proprietary BIONET Collection
Our proprietary BIONET product portfolio now contains over 80,000 R&D products that provide
a valuable resource for both FTE and custom synthesis projects. Many of our BIONET products
are available in Kg quantities and come with assured quality. Most are available in >97%
purity with full Certificate of Analysis that includes LC-MS and 400 MHz NMR data.
We add new BIONET products weekly through our own in-house R&D as well as external
alliances. We offer an unrivalled 100% guarantee for all of our BIONET products.
Key Endorsements
Our FTE-based collaborations involving medicinal and developmental
chemistry are regularly renewed and extended, demonstrating customer
confidence in our capabilities and ability to deliver outstanding results.
Endorsement by some of our recent customers:
“Over the past 6 years Key Organics
has successfully delivered both
FFS contracts and FTE contracts
for Heptares Therapeutics. I have
been particularly impressed with
the intellectual input provided
by Key Organics’ scientists,
their consistently high level of
productivity and their creativity
for providing innovative solutions
to difficult problems. We are
delighted with the success of our
collaborations with Key Organics
and are pleased to acknowledge the
important contribution they have
made to Heptares Therapeutics’
drug discovery efforts.”
Dr Giles A. Brown,
Associate Director Chemistry,
Heptares Therapeutics
“During a five year multiple FTE project, Key
Organics developed and assisted in patenting
a novel series of selective JAK3 inhibitors
and delivered over 200 compounds from
the initial hit to lead phase that resulted in
three candidates that had nm potency &
excellent JAK family selectivity. A granted
USA patent was obtained through their
input and contribution with PCT filings
pending in Europe, Japan & Canada. They
established and maintained an excellent
project management role with our biology
partner, Reaction Biology Corporation (RBC)
based in the United States and provided
an outstanding level of strategic as well as
hands-on synthetic chemistry throughout
the programme”.
Managing Director,
Synerga Limited.
Extensive, growing compound collection
Next-day courier delivery in EU
Dedicated customer support
>90% deliverable ex-stock
Novelty and Diversity
Same-day dispatch
High quality
Our BIONET Guarantees:
Intermediates
Fragment Libraries
Biochemicals
Screening Compounds
>80,000 Compounds
Products
“I have been extremely impressed by Key
Organics’ professionalism and candour during
separate multi-gram re-synthesis and route
development projects carried out recently.
In particular, Key communicated clearly
and rapidly with me when any obstacles to
project delivery were encountered. Their swift
and frank communication gave us time to
jointly devise solutions which ensured that
objectives were achieved while working to
tight deadlines. Key’s ability to formulate
innovative routes to important organic
compounds is also first rate. In this regard,
they dramatically improved the availability
of one of our crucial intermediates by
developing some neat chemistry that relied
upon unconventional thinking.”
Dr Matthew Fyfe,
Head of Chemistry,
TopiVert Pharma Ltd
