Mark R. Ashton, Evotecís Executive Vice President of
Business Development, describes the companyís strategy
to provide innovative technology for drug discovery and
development. Dr. Ashton talked to PharmaWeek
about Evotecís newly established Innovation Centre for
Fragment-Based Drug Discovery, its proprietary programs,
and the capabilities it brings to companies seeking an
outsourcing or collaborative research partner.
Briefly summarize Evotecís business model.
was established in the early 1990s as a contract research
organization. Our strategy then was and still is to be the
premier partner for pharmaceutical and biotechnology
companies through collaborative research or via the
partnering of our internal programs.
partnerships take different guises depending on the needs
of our partner, and the intellectual property and assets
Evotec brings to the table. Collaborations can manifest
themselves as simple fee-for-service agreements. Or they
can take the form of results-based
collaborations where Evotec accepts some of the research
risk in exchange for downstream milestone payments and
royalties. We also actively look to partner our internally
developed programs at various stages of preclinical and
clinical development, depending on the therapeutic area
and therefore the internal disease expertise that we have.
has significant disease biology experience around CNS,
which we have leveraged to build a pipeline of proprietary
CNS programs. Three of those programs are now in the
clinic. Our lead program, for insomnia, has successfully
completed its first Phase II trial. We will likely partner
our clinical programs at the end of Phase II when we have
established proof of concept in patients. We will advance
some of our preclinical CNS programs into the clinic on
our own and for others we will seek partners prior to the
also working on a number of proprietary programs in areas
such as oncology, inflammation, and metabolic disease.
These non-CNS programs are being generated using
Evotecís fragment-based drug discovery platform
(described in detail below). Because Evotec does not
necessarily have the same depth of disease biology
experience in these areas, we will look to partner these
programs early on, e.g., around establishment of in
vivo proof of principle.
Is Evotec shifting more toward building its proprietary
pipeline, or is there an equal emphasis on establishing
contract research partnerships?
Ashton: There is
very much an equal emphasis. Evotecís strategy is to
maximize shareholder value. To do that by just building
our own pipeline takes on significant risk. Our business
model allows us to balance the risk of building an
internal pipeline with our collaboration work, which
brings in revenues. For that reason, we will continue to
place equal emphasis on both sides of our business. We see
great synergies in both business models.
Describe Evotecís proprietary drug discovery
has a comprehensive IND engine. We have a proprietary
high-throughput screening platform that was developed in
partnership with Pfizer, Novartis, and GlaxoSmithKline. It
is an ultra high-throughput technology that allows us to
screen in excess of 100,000 compounds per day per
instrument using our proprietary detection technologies.
has its own 250,000-compound library. Using this library
and the screening instrument, weíre able to screen
against numerous biological targets to identify hits. Our
medicinal chemistry department progresses these hits
through lead optimization. Evotec has proprietary
computational chemistry software, as well as a structural
biology department to support the medicinal chemistry
activities. For example, if the protein is amenable to
X-ray crystallography we can use our structural biology
for structure-based drug design. Using these capabilities
we perform multi-parameter lead optimization, as well as
pre-formulation studies to examine key properties such as
salt forms and polymorphisms, to obtain the optimal
development candidate to take into the clinic.
Tell me about Evotecís recently announced Innovation
Centre for Fragment-Based Drug Discovery.
Fragment-based drug discovery is a state-of-the-art
technology that is being used more and more for certain
drug targets. While it still has some limitations, it can
be used for the majority of enzymes, protein-protein
interactions, and for certain protein targets that have
proved problematic in the context of a traditional
high-throughput screening approach.
has invested about two years in fragment-based drug
discovery and developed a technology called EVOlution. It
allows us to identify fragments for certain protein
targets. Whereas a traditional small-molecule hit from
high-throughput screening has a molecular weight of around
450 daltons, a fragment has a molecular weight of only
150Ė300 daltons. As a result, the fragment has a much
weaker interaction with its protein target, necessitating
very sensitive detection technology.
EVOlution technology can detect those very weak
interactions. We can do this in a high-throughput mode by
screening our library of over 30,000 fragments against
various protein targets. Once the fragment is identified,
it is optimized for potency and selectivity for the target
and for certain pharmacokinetic parameters. Fragment
optimization utilizes many traditional medicinal chemistry
skills. However, the challenges associated with fragment
optimization also require a lot of specific experience in
order to be efficient.
from fragment to lead is generally a quicker process than
for a high-throughput screening hit due to the
fragmentís small size. We can also generate crystal
structures of the protein-bound fragments so that we can
immediately identify what part of the fragment we need to
modify to improve its properties for drug functionality.
Does Evotec have ideas for future innovation centres?
Ashton: We plan
to set up further innovation centres over the next two years. We feel
these centres must be able to bring innovation to the drug
discovery process. Through the centres we want to decrease
attrition, increase the speed of drug discovery, identify
novel chemical matter for various biological targets, and
solve key biological pathways. Those four criteria must be
answered by the innovation centreís technology. We
believe fragment-based drug discovery is capable of
answering a number of those. Future innovation centres
will also be geared toward providing the pharmaceutical
industry with solutions to those challenges.
innovation centres can be envisioned as biotechs embedded
within Evotecís capabilities platform. There are a
number of companies that carry out fragment-based drug
discovery internally. Astex is a biotech company well
renowned for doing this type of research. So, one can
consider our innovation centre for fragment-based drug
discovery as a biotechóan Astex if you willóthat is
actually embedded within Evotecís infrastructure. The
difference is, the innovation centre has the immediate
advantage of being able to access all of Evotecís drug
discovery and development capabilities, which constitute a
critical mass far larger than can be found at most biotech
for more information about Evotec.
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