Summary of pipeline
Phase I	Phase II	Phase III	Filed
SB 275833	Bactroban*	Factive*	Factive
SB 249417	Ziagen*	tafenoquine (SB 252263)	Augmentin*
GW409544	SB 207266	GW433908	Malarone*
GW473178	SB 237376	Zeffix*	Epivir*
GW501516	enrasentan (SB 217242)	Valtrex/Zelitrex*	Trizivir
GW660511	GI198745	Relenza*	GI198745
SB 223412	ReQuip*	telmisartan*	Imigran/Imitrex*
SB 424323	Imigran/Imitrex*	Tranilast	Bexxar
SB 435495	Hycamtin*	GI262570	Seroxat/Paxil*
GI181771	GW320659 (1555U88)	nabumetone Q*	Flixotide/Flovent*
GW427353	GW650250	Naramig/Amerge*	Ventolin*
SB 418790	mepolizumab (SB 240563)	Hycamtin*	Seretide/Advair*
SB 273005	GR270773	Seroxat/Paxil*	Avandia*
GW406381	GW273293	Ariflo	Twinrix 3 doses (v)
GW468816	SB 596168	Flovent*	Infanrix PeNta – Hep B-IPV (v)
SB 271046	SB 683698 (TR14035)	Serevent*	Infanrix HeXa – Hep B-IPV/Hib (v)
SB 641257 (YH1885)	Ariflo	Seretide/Advair*	Boostrix (v)
GW572016	repifermin	Coreg*
SB 251353	SB 204269	Twinrix 2 doses (v)
SB 408075	GW150013	Extra strength Hepatitis B (v)
GW597599	SB 659746A (EMD 68843)	S pneumoniae (v)
SB 243213	N. Meningitidis A/C (v)	MMR-varicella (v)
GW328267	Rotarix (v)
fluticasone/salmeterol*	Epstein-Barr virus (v)
SB 223412	Malaria (v)
Hepatitis E (v)	Human papilloma virus (v)
New Influenza (v)	Simplirix (v)
HIV (v)	Meningitis B (Cuba) (v)
S. pneumoniae (v)	SB-M00026 (p)
GW/PowderJect technology (p)	SB 249553 (p)
	GW419458 (p)

The content of the drug development portfolio will change over time as new compounds progress from discovery to development and from development to the market. Owing to the nature of the drug development process, it is not unusual for some compounds, especially those in early stages of investigation, to be terminated as they progress through development.

For competitive reasons, new projects in pre-clinical development have not been disclosed and some project types may not have been identified.

These are described in more detail below.

There is now a clear focus on a unified approach to the generation and demonstration of commercial product value to customers. These customers include patients, healthcare professionals, budget holders and regulators, and each population has its own needs in terms of assessing the value of a new product. R&D is now positioned to ensure that, as well as developing the right products, it also generates the right information about these products. Increasingly this means not only safety, efficacy and quality information but also evidence of product value through measures such as overall reductions in healthcare utilisation, increasing length or quality of life and increased workplace productivity.

Early drug discovery and new technologies
Over the past five years both Glaxo Wellcome and SmithKline Beecham invested heavily in establishing and integrating new technologies that will harness the full therapeutic potential offered by the elucidation of the human genome. High-throughput (HT) technologies such as HT gene sequencing, HT chemistry and HT screening are now fully established and mean that GlaxoSmithKline has substantial resources to identify significant numbers of novel molecular targets, make structurally diverse compounds and efficiently screen these compounds against such targets. In addition, HT biology technologies will help us determine the most relevant therapeutic applications of new drugs modulating pathological mechanisms that may underpin several different diseases. These technologies are the cornerstone of activities within Genetics and Discovery Research and are designed to provide a steady stream of validated drug targets and suitable series of lead compounds to the newly-created Centres of Excellence for Drug Discovery.

Complementary to these new technologies has been the work carried out in Glaxo Wellcome over the past three years to develop ways of associating disease with a patient’s genetic make up. GlaxoSmithKline now aims to identify the genes most relevant to common diseases with large unmet medical needs, such as asthma, non-insulin dependent diabetes, migraine, osteoarthritis, metabolic syndrome, depression, chronic obstructive pulmonary disease, early onset heart disease and Alzheimer’s disease. To further these initiatives, large international collaborative studies have now been initiated for six of these diseases. These networks bring together clinicians and other experts in the diagnosis of these diseases with centres skilled in analysing genetic and clinical data.

Many of the applications of genetic science to healthcare will be driven by single nucleotide polymorphism (SNP) high-density mapping. This new technology can be likened to a road map, with SNPs acting as signposts that tell scientists where they are on the genome. Both Glaxo Wellcome and SmithKline Beecham were members of The SNP Consortium launched in April 1999. The consortium, which comprises 12 pharmaceutical and technology companies, five academic centres and The Wellcome Trust, is producing an ordered high-density SNP map of the human genome. This work has progressed ahead of schedule, and the data are being placed in the public domain.

Centres of Excellence for Drug Discovery
Both Glaxo Wellcome and SmithKline Beecham have experimented with a number of ways to manage drug discovery in order to optimise the progression of new medicines. During 2000, it was agreed that, for GlaxoSmithKline, a novel approach to the integration of late-stage discovery and early-stage development – the critical drug discovery phase – would be adopted. This approach is based on a sound understanding of the creative and entrepreneurial environment needed to enhance the scientific knowledge and expertise required to discover new drugs of proven value.

Six Centres of Excellence for Drug Discovery (CEDDs) have been created in GlaxoSmithKline, each focusing on specific disease areas, as summarised below:

CEDDs have the autonomy to select new compounds from either internal or external sources. Each CEDD is responsible for selecting the optimal candidate from a series of similar chemical compounds and for ensuring this candidate is safe in animal models and can be developed from a technical perspective. Once this is achieved, the CEDDs are responsible for conducting the pre-clinical and early clinical work required to prove that the compound is safe and efficacious in patients – the proof-of-concept or provision-of-confidence decision point. Following a thorough senior review of the information generated, a decision is then made to progress the compound into late stage drug development where the necessary large-scale clinical trials are conducted to successfully register and commercialise the product.

New product development
To provide focus for the development and commercialisation process, which must proceed in unison, all the major functional components, Medical, Regulatory and Product Strategy, have been integrated into one management organisation. Late-stage product development in both Glaxo Wellcome and SmithKline Beecham was organised by therapeutic areas and eight such areas have been identified for GlaxoSmithKline:

Worldwide vaccines R&D is conducted by the Biologicals Division, located principally at Rixensart, Belgium. It is managed independently from pharmaceuticals development. However, essentially similar approaches to development are adopted for both vaccines and prescription medicines.

The eight pharmaceutical therapy areas and vaccines development are managed by cross-functional matrix teams responsible for maximising the worldwide development opportunities for each product. The teams work to ensure that there is alignment between regional marketing needs and the clinical and commercial information generated for a new product as it is developed. The teams also collaborate at an early stage with integrated technical development and manufacturing functions to ensure rapid, effective launch and delivery of the product.

By increasingly incorporating genetic research into clinical trials of new and innovative medicines, GlaxoSmithKline will enable healthcare providers to prescribe medicines more accurately based on a patient’s predicted response profile (in terms of both drug safety and efficacy). In addition, genetic research will enable a better understanding of the causes of common diseases. Many such diseases arise through complex interactions between a number of gene variants and environmental factors. Identifying the genes that predispose patients to a particular disease and understanding their role in disease progression will lead to the identification of new ways to intervene in these diseases. This understanding will also provide greater confidence that existing drug targets are relevant to the disease.

New product supply
The efficient delivery and rapid worldwide uptake of our new products are closely linked to their ease of manufacture. Such issues as scale-up and manufacturing technology are considered at an early stage of product development, so that the process of moving from small-scale production of experimental materials for early clinical studies through to large-scale industrial manufacturing for product supply can be fast and efficient. This is the responsibility of ‘New Product Supply’, a partnership between R&D preclinical staff and Global Manufacturing & Supply. The partnership ensures that the Development organisation delivers a product that has already been optimised in terms of large-scale commercial manufacturing.

Animals and research
For ethical, scientific and legal reasons, animal experimentation remains essential in the discovery and subsequent safety evaluation of new medicines. GlaxoSmithKline policy is to replace animal experiments where at all possible and use alternatives such as in vitro cell culture or computer modelling techniques. If animal experiments are unavoidable, our approach is to seek to reduce the number of animals used, through improved techniques and methodology. Examples of this approach include:

Additionally, every effort is made to minimise discomfort in those animals used for such studies.


Research and development – Consumer Healthcare

The principal centres for Consumer Healthcare research and development are in the UK and in the USA. Consumer Healthcare liaises closely with Pharmaceuticals to ensure that commercial opportunities in the OTC field are identified as quickly as possible. GlaxoSmithKline also pursues, whenever possible, opportunities to switch prescription products to OTC products.