GSK Annual Report 2002

20 GlaxoSmithKline Description of business
In R&D the power of smaller units is manifest in the Centres of
Excellence for Drug Discovery (CEDD). They ensure the most
efficient and rapid validation of lead candidates through preclinical
testing against proof of concept criteria, before handing over the
compound to the New Product Development organisation for large
scale clinical trials.
The New Product Development function integrates the clinical,
regulatory and commercial activities necessary to bring a new
medicine to the marketplace. Similarly, the New Product Supply
organisation bridges the traditional divide between development
and manufacturing, ensuring that robust manufacturing processes
are developed.
Significant progress has also been made in the integration of the
Group’s R&D in Japan with the global development and
commercialisation processes in order to eliminate duplication and
to speed up regulatory filings. During 2002 the discovery and
development portfolio in Japan was reviewed and prioritised in the
context of the global R&D pipeline.
Crucial to the success of R&D is its capacity to embrace and
develop new technologies to streamline the drug discovery process.
The technology development organisation keeps abreast of
emerging technologies that may advance the creation of new
medicines, evaluates them and provides the investment and
knowledge required to develop selected technologies appropriately.
As R&D generates and modifies technologies, it will not only focus
them on the Group’s internal goals but also maximise the return on
R&D assets through sales, spin-outs and out-licensing.
Early research and the role of genetics
The early stages of finding new medicines requires essentially two
components; targets that can be shown to affect mechanisms of
important pathological processes in human disease and
compounds, typically small molecules but also including
macromolecules, protein therapeutics and vaccines, able to
modulate the behaviour of specific targets.
As part of this target validation process, GlaxoSmithKline aims to
identify the genes most relevant to common diseases with large
unmet medical needs, such as asthma, non-insulin dependent
diabetes, osteoarthritis, chronic obstructive pulmonary disease,
early onset heart disease and Alzheimer’s disease. Many diseases
arise through complex interactions between a number of gene
variants and environmental factors, so the challenge involved is
significant. Identifying the genes that predispose patients to a
particular disease and understanding their role in its progression
lead to finding new ways to intervene in these diseases.
In 2002, a programme to identify tractable targets that are
genetically associated with human diseases of interest was
initiated. This enables the validation of targets associated with
these diseases prior to extensive investigation.
The practical application of genetics has moved forward during
the year. Several opportunities have been identified where
knowledge of specific markers for efficacy or susceptibility to
adverse events is enhancing the ability to focus development of
new medicines on patients who will be most likely to benefit from
them, ultimately providing reassurance to both the prescriber and
the patient.
Discovery research
The purpose of Discovery Research (DR) is to identify lead
compounds that may form the basis of drug discovery efforts in
the CEDDs. Investment in DR is focused on improving productivity
in both quality and quantity. In 2002, R&D completed construction
of new automation facilities at Tres Cantos, in Spain, and
continued work on facilities at Upper Providence and Harlow.
In parallel with the development of the ability to generate
efficiently large numbers of high quality new compounds, there
has been substantial progress in implementing methods to evaluate
them using high throughput biology. This discipline, with its
integration of knowledge from both animal and human biology,
is starting to deliver highly predictive models to forecast efficacy
of compounds and to extend understanding of human disease.
Centres of Excellence for Drug Discovery
The two crucial steps in converting lead compounds into drug
candidates are (i) optimising the lead for potency, efficacy, safety
and other intrinsic characteristics of the molecule, and (ii)
demonstrating the validity of the therapeutic hypothesis through
early clinical trials of the resulting candidate. The CEDDs are
focused on specific disease areas and designed to be nimble and
entrepreneurial with the range of skills and resources required to
drive mid-stage development projects from lead optimisation
through to their key decision-point, demonstration of proof of
concept, before major investments are made to fund large-scale
clinical trials.
There are six CEDDs, three based in the USA and three in Europe:
• Cardiovascular & Urogenital Diseases, centred in Upper
Merion
• Metabolic & Viral Diseases, centred in Research Triangle Park
• Microbial, Musculoskeletal & Proliferative Diseases, including
cancer, centred in Upper Providence
• Neurology, centred in Harlow (UK)
• Psychiatry, centred in Verona (Italy)
• Respiratory and Inflammation, centred in Stevenage (UK).
Each CEDD is responsible for identifying the optimal drug
candidate for the desired biological effect and then assessing its
safety and other development characteristics in preclinical screens.
Once this is achieved, the CEDDs are responsible for proving that
the compound is safe and efficacious in patients in small-scale
clinical trials – the proof of concept decision point.
A decision is then made on whether the information available to
date justifies the compound’s progression into late-stage drug
development where the necessary large-scale clinical trials are
conducted to register and commercialise the product.
In 2002, the CEDDs progressed significantly more compounds
through both first dosing in humans and initial evaluation of
efficacy in patients than in 2001. See table of compounds
progressed into Phase I on page 18. In order to progress highly
promising medicines yet more rapidly without compromising safety,
selected projects are currently piloting a process that involves
running some activities in parallel, rather than sequentially.