Xenova Group PLC
21 October 2003
FOR IMMEDIATE RELEASE
Xenova Group plc
Xenova Statement on Imperial College Research
Into Novel Strategy for Treatment of Flu
Slough, UK, 21 October, 2003 - Xenova Group plc (NASDAQ NM: XNVA; London Stock
Exchange: XEN) notes that the following announcement was issued late yesterday
by Imperial College with respect to a research collaboration involving the
company's OX40 technology and its potential for the treatment of influenza.
OX40 is a platform technology capable of producing multiple drug candidates
targeting cancer, autoimmune and other diseases where the immune system is
David Oxlade, Chief Executive of Xenova, said, 'We are very encouraged by these
novel findings from the work conducted by Imperial College on our OX40 platform
technology. The demonstration in pre-clinical studies that down-regulation of
the immune response by blocking the OX40-OX40 ligand interaction alleviates the
symptoms of influenza, without affecting the ability to clear the virus, is very
exciting. This new research suggests that the down-regulation of OX40 signaling
could play an important role in the fight against the symptoms of influenza and
perhaps other diseases similarly characterised by excessive immune response'.
Xenova's rights to the OX40 technology include rights relating to the
up-regulation of the immune system which may be used for the development of
novel treatments for cancer and infectious disease. Xenova's rights to
down-regulate the immune system have been the subject of development and licence
agreements entered into with Celltech and Genentech.
The full text of the Imperial announcement follows overleaf:
- ends -
Xenova Group plc Trout Group/BMC Communications
Tel: +44 (0)1753 706600 Tel: 001 212 477 9007
David A Oxlade, Chief Executive Officer Press: Brad Miles (Ext 17)
Daniel Budwick (Ext 14)
Daniel Abrams, Group Finance Director Investors: Jonathan Fassberg
(Ext 16) Lee Stern (Ext 22)
Jon Davies, Corporate Communications
Tel: +44 (0)207 831 3113
David Yates/Ben Atwell
Notes to Editors
Xenova Group plc's product pipeline focuses principally on the therapeutic areas
of cancer and immune system disorders. Xenova has a broad pipeline of
programmes in clinical development. The Group has a well-established track
record in the identification, development and partnering of innovative products
and technologies and has partnerships with significant pharmaceutical and
biopharmaceutical companies including Lilly, Pfizer, Celltech, Genentech, QLT
and Millennium Pharmaceuticals.
Inflammation is part of the body's normal response to the presence of infection
or other unwanted foreign material. In certain circumstances this process can
cause damage to the body's own tissues. In many cases this pathology is
orchestrated by activated T cells. Consequently drugs that are capable of
inhibiting the action of these activated T cells have potential as therapeutics
for control of inflammatory disease.
OX40 is a receptor molecule found on the surface of activated T cells at the
site of inflammation and offers an important potential target for development of
a selective inhibitor of inflammation. Through collaboration and license
agreements with Stanford University, and the Providence Medical Center,
Portland, Xenova has intellectual property covering therapeutic use of the OX40
and OX40 Ligand proteins and their related antibodies.
Xenova has developed a modified form of the OX40 molecule which can be used to
block the interaction between the OX40 receptor and its ligand and hence inhibit
T cell activation. This product candidate has been shown effective in a
preclinical model of autoimmune disease, and has moved into preclinical
Development of a monoclonal antibody against OX40 presents an alternative
approach to target and destroy OX40-bearing activated T cells and hence treat
autoimmune disease. This strategy is being pursued by Celltech Group under a
license agreement with Xenova, which began in September 1999.
A development and license agreement worth up to $63m (£43.2m) was signed in
April 2002 with Genentech Inc ('Genentech') for the worldwide rights to develop
and market products, primarily targeting disorders of the immune system, based
on Xenova's OX40 receptor protein and anti-OX40 Ligand antibody programs. Under
this agreement, Xenova retains all rights to the up-regulation of the immune
system using the OX40:OX40L interaction, including for use in oncology and
infectious disease therapy.
For further information about Xenova and its products please visit the Xenova
website at www.xenova.co.uk
For Xenova: Disclaimer to take advantage of the 'Safe Harbor' provisions of the
US Private Securities Litigation Reform Act of 1995. This press release contains
'forward-looking statements,' including statements about the discovery,
development and commercialization of products. Various risks may cause Xenova's
actual results to differ materially from those expressed or implied by the
forward looking statements, including: adverse results in our drug discovery and
clinical development programs; failure to obtain patent protection for our
discoveries; commercial limitations imposed by patents owned or controlled by
third parties; our dependence upon strategic alliance partners to develop and
commercialize products and services; difficulties or delays in obtaining
regulatory approvals to market products and services resulting from our
development efforts; the requirement for substantial funding to conduct research
and development and to expand commercialization activities; and product
initiatives by competitors. For a further list and description of the risks and
uncertainties we face, see the reports we have filed with the Securities and
Exchange Commission. We disclaim any intention or obligation to update or
revise any forward-looking statements, whether as a result of new information,
future events or otherwise.
Imperial researchers show novel flu treatment eliminates symptoms in mice
Imperial College London researchers report today in the Journal of Experimental
Medicine that they have developed a novel strategy for effectively treating the
symptoms of the most deadly type of flu.
Working with influenza A virus, they show in mice that their novel treatment
eliminates symptoms by reducing the response of active T white blood cells by a
Flu A is the type of influenza responsible for pandemics such as the 1919
outbreak of 'Spanish flu', which globally killed more than 20 million people.
Unlike current attempts to prevent or treat flu, which rely on either yearly
vaccinations that try to predict how the virus might mutate, or anti viral drugs
that must be administered as soon as there is contact with the virus, this new
treatment can be given after symptoms present.
Dr Tracy Hussell of Imperial's Centre for Molecular Microbiology and Infection
and senior author of the paper says: 'Three times in recent history the flu
virus has evolved from a disease characterised by coughs and sneezes to a world
killer. The recent SARS epidemic highlights how quickly a deadly virus can
spread in modern society and we are long overdue for the next flu pandemic. The
sobering reality is that influenza is one of the grand masters at evading human
'During flu infection the immune system has an 'all hands on deck' attitude to
the viral assault. But it's this that causes most of the damage. The exaggerated
immune response produces inflammatory molecules that lead to what's known as a
'cytokine storm'. Essentially too many cells clog up the airways and prevent
efficient transfer of oxygen into the bloodstream.
'By selectively reducing this cellular load we've shown it's possible to
eliminate clinical symptoms whilst effectively tackling and clearing the
The body has two major classes of white blood cells, T and B lymphocytes. While
B cells produce tailor-made antibodies that help the body remember and quickly
respond to invaders, T cells patrol the body, seek out and destroy diseased
cells. But the T cell response also produces inflammatory mediators that lead to
the 'cytokine storm'.
Until now, treatments to eliminate the cytokine storm have focused on inhibiting
all T cells. But this leaves the patient unable to clear the virus and
susceptible to other infections. Dr Hussell's team have developed a way of down
regulating a molecule known as OX40 that only targets T cells that have recently
been alerted to the presence of the flu virus.
'OX40 sends out a 'survival signal' instructing activated T cells to remain in
the lungs for longer to help fight the infection. However, because new cells are
arriving all the time this prolonged presence is not needed,' explains lead
researcher Ian Humphreys of Imperial's Centre for Molecular Microbiology and
'Inhibiting this signal therefore allows T cells to vacate the lungs earlier
whilst leaving behind a sufficient immune presence.'
Using a fusion protein OX40:Ig supplied by the pharmaceutical company Xenova
Research, the scientists were able to demonstrate that OX40:Ig blocks active T
Results show six days after infection with flu, mice treated with OX40:Ig were
indistinguishable from uninfected control mice. But infected mice that had not
been treated lost 25 per cent of their body weight, appeared hunched, withdrawn
and lost their appetite - all characteristic symptoms of flu.
When treatment with OX40:Ig was delayed for several days after infection, until
the mice had lost 20 per cent of their body weight and OX40:Ig was administered,
symptoms were reversed.
Re-infection also indicated that the ability of mice to respond to a second
infection was not affected by the reduced T cell immunity during the initial
Dr Hussell added: 'There is tremendous scope for this treatment. Basically any
disease that is characterised by an excessive T cell inflammatory response,
whether in the lungs, in the case of Bronchitis, Asthma and Pneumonia, or in the
joints, such as Rheumatoid arthritis, could be a candidate for this type of
treatment. If the clinical symptoms of SARS are caused by excessive immune
responses it too could be effectively treated.'
For further information, please contact:
Judith H Moore
Imperial College London Press Office
Tel: +44 (0)20 7594 6702
Mobile: +44 (0)7803 886 248
Notes to editor
Journal: Journal of Experimental Medicine
Title: 'A critical role for OX40 in T Cell mediated immunopathology during lung
Authors: Humphreys, Ian R (1); Walzl, Gerhard (1); Edwards, Lorna (1); Rae,
Aaron (1); Hill, Sue (2); Hussell, Tracy (1).
(1) Imperial College London, Exhibition Road, London SW7 2AZ, UK
(2) Xenova Research Ltd, 310 Cambridge Science Park, CB4 0WG
Facts about flu
There are three main types of influenza virus A, B and C. Of these, A and B are
of most concern because of the way in which their genomes evolve.
The organisation and type of genetic material flu virus is made from helps it
hide from the immune system. RNA viruses, such as flu have a higher mutation
rate because they don't proof check their genetic material when they make new
viral particles. As a result, there's a huge amount of genetic variability
within a new generation of virus particles. Although many of the mutation will
be detrimental there will be enough that are able exploit a weakness in the
Influenza A is particularly dangerous because it readily undergoes 'gene
swapping' or reassortment. This means two strains of the virus can infect the
same cell and swap genetic information. Add this to influenza's ability to
infect certain animals and birds, and you have a situation where two very
distinct strains can infect a cell and hybridise to create a new strain that is
very different from anything the immune system has encountered before. It is
this process of gene swapping that has been linked with the emergence of most
About Imperial College London
Consistently rated in the top three UK university institutions, Imperial College
London is a world leading science-based university whose reputation for
excellence in teaching and research attracts students (10,000) and staff (5,000)
of the highest international quality.
Innovative research at the College explores the interface between science,
medicine, engineering and management and delivers practical solutions that
enhance the quality of life and the environment - underpinned by a dynamic
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