Final Results
Oxford Biomedica PLC
21 March 2005
FOR IMMEDIATE RELEASE 21 MARCH 2005
OXFORD BIOMEDICA PLC
PRELIMINARY RESULTS FOR THE YEAR ENDED 31 DECEMBER 2004
Oxford, UK - 21 March 2005: Oxford BioMedica (LSE: OXB), the leading gene
therapy company, today announces its preliminary results for the year ended 31
December 2004. Highlights:
Oncology
• TroVax: Phase II results in colorectal cancer alongside chemotherapy
exceeded expectations, demonstrating immune responses in all patients and
clinical benefit in the majority. Announced on 2 March 2005
• TroVax: Phase I/II follow-up analysis showed a highly significant
correlation between immune responses and time to disease progression
• TroVax: Phase II trial in renal cell carcinoma commenced in the United
States
• TroVax: commercial manufacture established with over 22,000 doses
produced
• TroVax: plans for registration trials to be discussed with the FDA
imminently
• Anti-5T4 targeted antibody: Wyeth completed its preclinical evaluation
and clinical trials are under consideration
• MetXia: Phase I rolling to Phase II trial in pancreatic cancer underway
Neurotherapy
• ProSavin: preclinical results showed almost complete recovery in movement
behaviour in Parkinson's disease
• ProSavin: regulatory discussions ongoing prior to formal submissions for
clinical trials
• MoNuDin: preclinical results demonstrated a highly significant increase
in life expectancy in ALS, published in Nature
• SMN-1G: preclinical results showed a statistically significant
improvement in survival in spinal muscular atrophy, published in the
Journal of Clinical Investigation
• Innurex: preclinical results showed restoration of limb function in
avulsion or stretch injury
Technology licensing
• Four technology licensing agreements signed during 2004 and another since
the year end, generating sustainable revenue
• Merck & Co and Biogen Idec licensed the LentiVector technology for
research use
• Viragen licensed the LentiVector technology for biomanufacturing using
avian transgenics
• MolMed licensed the retroviral ex vivo gene delivery technology for
therapeutic applications
Financial
• Revenue for the year ended 31 December 2004 increased 34 per cent to £0.5
million (2003: £0.4 million) reflecting growing income from licensing
• Loss before tax and exceptional items for the year reduced to £11.1
million (2003: £12.7 million)
• Operating expenses for the year were essentially unchanged at £13.5
million (2003: £13.7 million)
• Cash and short term investments at 31 December 2004 of £22.4 million
(2003: £31.8 million)
• Cash resources sufficient to support development activities into 2007,
before taking account of new licensing agreements
Board appointment
• Nick Woolf, Senior Vice President for Corporate Strategy, appointed to
the Board as an executive director on 3 March 2005
Commenting on the results, Oxford BioMedica's Chief executive, Professor Alan
Kingsman said: 'We have made good progress during 2004 in both product
development and licensing. In particular, the recent successful Phase II results
with TroVax have confirmed the potential for our lead product. The value of our
technology platforms is also becoming evident. In 2004 and since the year end,
we have secured five technology licensing deals, which are generating growing
and sustainable revenue. More deals on technology and products are expected. At
the same time, we are moving TroVax towards registration trials and taking the
lead neurotherapy products towards clinical development. With our solid cash
position, we are well placed to deliver on our objectives. We look forward to
the coming year as our products and technologies advance towards
commercialisation.'
-Ends-
For further information, please contact:
Oxford BioMedica plc:
Professor Alan Kingsman, Chief Executive Tel: +44 (0)1865 783 000
City/Financial Enquiries:
Lisa Baderoon/ Mark Court/ Mary-Jane Johnson Tel: +44 (0)20 7466 5000
Buchanan Communications
Scientific/Trade Press Enquiries:
Sue Charles/ Katja Stout/ Ashley Lilly Tel: +44 (0)20 7886 8150
Northbank Communications
Notes to editors
1. Oxford BioMedica
Oxford BioMedica (LSE: OXB) is a biopharmaceutical company specialising in the
development of novel gene-based therapeutics with a focus on the areas of
oncology and neurotherapy. The Company was established in 1995 as a spin out
from Oxford University, and is listed on the London Stock Exchange.
Oxford BioMedica has core expertise in gene delivery, as well as in-house
clinical, regulatory and manufacturing know-how. In oncology, the pipeline
includes an immunotherapy and a gene therapy in multiple Phase II trials, and a
preclinical targeted antibody therapy in collaboration with Wyeth. In
neurotherapy, the Company's lead product is a gene therapy for Parkinson's
disease, which is expected to start clinical trials in 2006, and four further
preclinical candidates. The Company is underpinned by over 80 patent families,
which represent one of the broadest patent estates in the field.
The Company has a staff of approximately 65 split between its main facilities in
Oxford and its wholly owned subsidiary, BioMedica Inc, in San Diego, California.
Oxford BioMedica has corporate collaborations with Wyeth, Intervet, Amersham,
Viragen, MolMed and Kiadis; and has licensed technology to a number of companies
including Merck & Co and Biogen Idec.
Further information is available at www.oxfordbiomedica.co.uk.
Chairman's and Chief Executive's Report
Oxford BioMedica made good progress in product development and licensing during
2004. The company's primary goals were achieved in another successful year. Both
the oncology and neurotherapy pipelines have advanced. The lead anti-cancer
products, TroVax(R) and MetXia(R), are being evaluated in multiple clinical
trials, and the lead neurotherapy product, ProSavin(R) for Parkinson's disease,
is in manufacturing scale-up for clinical trials. Furthermore, the company's
licensing activities for its gene delivery technologies are generating
sustainable revenue. Four licensing agreements were signed in 2004, and an
additional licensee has been secured since the year end.
In oncology, over 70 patients have now been treated with TroVax, Oxford
BioMedica's advanced cancer immunotherapy product, in five clinical trials in
colorectal cancer and renal cell carcinoma. Clinical data reported during 2004
and on 2 March 2005 from the Phase I/II and Phase II trials confirmed the
excellent safety profile of TroVax, its ability to mount a consistent
anti-cancer immune response, and its potential to improve both time to disease
progression and survival of patients. The company is entering discussions with
the FDA for the design of randomised trials with TroVax that could form the
basis of a registration application and potential approval in 2008-09. While
partnership discussions continue, Oxford BioMedica is adding substantial value
to the product through its clinical development programme.
The second clinical product candidate, MetXia for pancreatic cancer, is
similarly progressing in clinical trials. The initial safety stage of the Phase
I rolling into Phase II trial in pancreatic cancer is ongoing and there have
been no adverse events associated with MetXia. The efficacy stage of the trial
is expected to commence in the first half of 2005 and the company anticipates
preliminary efficacy data before the end of the year with final results in 2006.
The collaboration with Wyeth on the targeted antibody therapy for cancer has
advanced successfully in 2004 following Wyeth's decision to exercise its option
on the product at the end of 2003. Wyeth has completed its preclinical
evaluation, process development is underway and clinical trials are under
consideration.
In neurotherapy, the therapeutic potential of Oxford BioMedica's LentiVector(R)
technology was strengthened in 2004. The company reported preclinical efficacy
data in Parkinson's disease, motor neuron disease, spinal muscular atrophy and
spinal cord injury. Some of the data were published in leading scientific
journals in 2004, validating the potential of these products and the LentiVector
platform. Ongoing and new sponsorship from US charitable research organisations
provided a further endorsement during 2004. ProSavin for Parkinson's disease is
on track for clinical trials despite some minor delays in manufacturing
scale-up. Oxford BioMedica expects to make its first regulatory submission for
the start of trials with ProSavin in the second half of 2005.
The company's LentiVector and proprietary gene delivery technologies have become
a source of sustainable revenue and deal generation. In 2004, the company
implemented a licensing initiative for its technologies as tools in research,
drug discovery and gene therapy. Since the beginning of 2004, Oxford BioMedica
has signed five licensing agreements with leading companies, including Merck &
Co and Biogen Idec. These agreements have secured upfront and annual maintenance
payments as well as the potential for milestone and royalty payments in some
instances. Further licensing deals are anticipated.
Oncology
Oxford BioMedica is developing novel cancer therapies that deliver a combination
of improved efficacy and safety. The company has created three major
opportunities in this area: TroVax, an active immunotherapy; MetXia, a
potentiator of cyclophosphamide chemotherapy; and a targeted antibody therapy,
partnered with Wyeth.
TroVax(R)
TroVax is Oxford BioMedica's advanced cancer immunotherapy product. It is
designed to stimulate an anti-cancer immune response and has potential
application in most solid tumour types. TroVax targets the tumour antigen 5T4,
which is broadly distributed throughout a wide range of solid tumours. The
product consists of a pox virus (MVA) gene transfer system, which delivers the
gene for 5T4. MVA is known to induce the breaking of immune tolerance to
self-antigens that are expressed from the gene delivery system.
Novel cancer immunotherapy products, such as TroVax, could provide new and
powerful weapons in the arsenal of anti-cancer treatments. In 2004, Oxford
BioMedica achieved a number of important milestones in its development of
TroVax. Over 70 patients have now been treated in clinical trials with TroVax.
The clinical programme could see the total number of patients treated with
TroVax increase to over 200 in the next 12 months.
There are four Phase II trials ongoing, three in colorectal cancer and one in
renal cell carcinoma. A Phase II trial in breast cancer is also expected to
start later in the year. A major US clinical trials consortium, the Southwest
Oncology Group, will conduct the breast cancer trial, at minimal cost to Oxford
BioMedica. Recent data, reported on 2 March 2005, from the Phase II trials in
colorectal cancer have been highly encouraging, and the company is now planning
pivotal trials. The development strategy is designed to generate data from
pivotal trials that could support initial product registration for TroVax in the
United States in 2008-09.
In preparation for pivotal trials and potential product registration, the
manufacturing process has been upgraded for commercial production of TroVax.
Oxford BioMedica signed a contract in 2003 with a major biologicals
manufacturer, which led to the successful scale-up of manufacture during 2004.
The company now holds over 22,000 doses of commercial-grade material.
The following sections provide a detailed update of the trials in colorectal
cancer, renal cell carcinoma and breast cancer, and also the development
strategy for initial product registration of TroVax.
TroVax in Colorectal Cancer
In March 2004, Oxford BioMedica's scientists presented survival data from the
completed Phase I/II trial with TroVax as a single agent in second line
treatment of patients with metastatic colorectal cancer at the American
Association for Cancer Research meeting. Five of the 17 evaluable patients
showed tumour responses following treatment with TroVax. In addition, a more
recent analysis showed a highly significant correlation between the magnitude of
patients' immune response to TroVax and time to disease progression. This
translated into a correlation with improved overall survival.
Standard of care for first line treatment of metastatic colorectal cancer tends
to be the chemotherapy combination of 5-fluorouracil and leucovorin with either
irinotecan, usually referred to as IFL, or oxaliplatin, denoted as FOLFOX. A new
drug for first line treatment received approval from the FDA in February 2004.
The product, AvastinTM (bevacizumab) from Genentech and Roche is approved for
use in combination with 5FU-based chemotherapy regimens, including both IFL and
FOLFOX, although a drug warning was issued in August 2004 that links the product
to an increased risk of blood clots.
Oxford BioMedica started two open label Phase II trials in first line treatment
of metastatic colorectal cancer in 2003. These trials were designed to
investigate whether concomitant chemotherapy affected patients' immune responses
to TroVax. Enrolment in both trials was completed in September 2004. In the
TroVax plus IFL trial, 19 patients have been recruited. The treatment regimen
comprises six immunisations of TroVax and up to 12 cycles of the chemotherapy
combination. The TroVax plus FOLFOX trial has recruited 17 patients, similarly
receiving six immunisations of TroVax alongside chemotherapy. The recruitment
objective of these two trials is to have at least ten evaluable patients in each
setting.
On 1 September 2004, the company reported that the primary endpoints in these
two trials were likely to be achieved based on preliminary data from 13 patients
who had reached the interim analysis point, defined as four TroVax immunisations
and more than eight cycles of chemotherapy. Of these patients, 11 (85 per cent)
had mounted antibody and/or cellular anti-5T4 immune responses.
These encouraging results have been confirmed as the trials have progressed. On
2 March 2005, the company reported that the primary endpoints of safety and
immunological responses had been achieved and that the secondary endpoint of
clinical benefit had exceeded expectation. Twenty-five patients have now been
assessed at the interim stage of the trial. There have been no serious adverse
events attributed to TroVax treatment and the number of patients mounting an
immune response has risen to 100 per cent, with all 25 patients showing antibody
and/or cellular responses to the tumour antigen.
Furthermore, 19 patients have now been assessed for tumour responses (tumour
stabilisation and tumour shrinkage), having received at least three TroVax
immunisations and one or more computed tomography scans. Patients entered the
trial with progressive disease, and 18 of 19 patients had a tumour response
following treatment. Thirteen of 19 patients were classified as clinical
responders, comprising three complete and ten partial responses.
To set these results in context, two independent studies of the chemotherapy
regimens alone, IFL and FOLFOX, reported clinical response rates in evaluable
patients of 41 and 50 per cent* respectively (Douillard et al., The Lancet 2000,
vol 355, pp 1041-1047; de Gramont et al., Journal of Clinical Immunology 2000,
vol 18, pp 2938-2947). It should be noted, however, that a precise comparison
with the TroVax trials is not possible owing to differences in the trial
protocols and patient numbers.
Data from the two Phase II trials of TroVax will be presented at the American
Society of Clinical Oncology meeting in Orlando, Florida, USA, in May 2005. The
trials are on track to report full safety and immunological data as well as
final tumour response statistics in the second half of 2005. Patient survival,
which can be compared to historical controls, will be reported once the median
survival has been reached in the two trials. This is anticipated towards the end
of 2005.
In January 2004, an investigator initiated, open label Phase II trial started,
with sponsorship from Cancer Research UK, in colorectal cancer patients who have
operable liver metastases. Patients receive TroVax immunisations before surgery
(neoadjuvant) and after surgery (adjuvant). Recruitment into this 20-patient
trial is over halfway completed.
On 2 March 2005, the company provided an update on the trial status. Eleven
patients have received the initial regimen of TroVax immunisations, but two were
subsequently withdrawn for being ineligible for surgery. All eight of the
remaining patients, who could be assessed, achieved the primary endpoint of
immune responses to the 5T4 tumour antigen, and were eligible for further TroVax
doses. The most recent patient has not progressed far enough through the trial
to assess immune responsiveness. TroVax has been safe and well tolerated in all
patients treated to date in this trial.
The treatment schedule comprises two immunisations with TroVax before and after
liver surgery and, potentially, a further two vaccinations. The endpoints of the
study are safety, immunological responses to 5T4 and clinical benefit. Following
surgery, these patients have a lower tumour burden and longer survival
expectation than patients in Oxford BioMedica's other Phase II trials in
colorectal cancer. This potentially makes them even more responsive to
immunotherapy approaches such as TroVax. Patients are generally not given
chemotherapy following liver surgery and there is a need for safe and effective
treatments to prevent disease relapse.
The preliminary results from this Phase II trial of TroVax in the (neo) adjuvant
setting will be presented on 22 March 2005 at the Keystone Symposia on Basic
Aspects of Tumour Immunology in Keystone, Colorado, USA. Cancer Research UK
plans to publish the full results in an appropriate clinical journal once the
trial is completed.
More than 65 patients with colorectal cancer have been treated with TroVax to
date in four clinical trials. Across all the trials, the safety profile of
TroVax has been excellent and the majority (98 per cent) of assessable patients
(50 patients) have mounted immune responses following treatment with TroVax.
This is an exceptionally high response rate in the context of clinical studies
with other cancer vaccines (Mocellin et al., Lancet Oncology 2004, vol 5: pp
681-689). TroVax has been investigated in different settings in these trials -
first line treatment with chemotherapy, second line treatment and the (neo)
adjuvant setting with surgery - and has achieved its primary endpoints in each
trial.
The immunological data emerging from the Phase II trials in colorectal cancer
suggest that the magnitude and duration of immune responses may be even greater
in first line treatment with concomitant chemotherapy and in the (neo) adjuvant
setting with surgery than in the Phase I/II studies in second line treatment.
When considered together with the high level of tumour responses, there is
growing evidence that TroVax may have therapeutic potential across all stages of
colorectal cancer, supporting the notion that the product may reach large
markets in this disease.
TroVax in Renal Cell Carcinoma
Oxford BioMedica believes that metastatic renal cell carcinoma (RCC) also
presents a prime opportunity for the development of TroVax. To date, neither
radiation, chemotherapy, nor hormonal therapy prolongs the survival of
metastatic RCC patients. Commonly used treatments for patients with metastatic
RCC include cytokines such as interferon-alpha, which has limited efficacy, and
interleukin-2, which is associated with severe side effects. About 40 per cent
of patients with RCC develop metastases after surgery.
Analyses of sample tissues from patients with RCC have shown that the 5T4 tumour
antigen is present at high levels on approximately 90 per cent of tumours.
Hence, RCC is a logical target for a 5T4-targeted immunotherapeutic. The number
of patients with metastatic RCC means that TroVax is likely to qualify for
Orphan Drug designation in this indication, which confers various benefits in
development and commercialisation. In addition, TroVax may also receive Fast
Track designation, which is designed to expedite the review process of drug
candidates that address life threatening diseases where there is an unmet
medical need for new therapeutic approaches. With Fast Track designation, there
is the opportunity for more frequent interactions with the FDA and the
possibility of a Priority Review, which could shorten the standard review
period.
Oxford BioMedica initiated a Phase II trial in first line treatment of
metastatic RCC at the Presbyterian Hospital, Columbia University Medical Center
in New York, New York, USA, in 2004. The FDA approved the company's IND
application in April 2004 and recruitment is ongoing. The open label trial is
designed to evaluate TroVax in combination with high dose interleukin-2
treatment in approximately 25 patients. The trial is on track to report
preliminary results on safety and immunological responses in mid-2005.
TroVax in Breast Cancer
In 2004, the US Southwest Oncology Group (SWOG), a clinical trials consortium
sponsored by the National Cancer Institute (NCI), established plans for a large
multicentre trial with TroVax in late stage (Stage III/IV) breast cancer. This
Phase II trial, the first with TroVax in breast cancer patients, will be
conducted and funded by SWOG. The proposed trial plan, announced in March 2004,
is an open label study to recruit 120 patients with Stage III/IV breast cancer.
The start of the trial has been delayed by a few months owing to minor revisions
requested by the NCI. However, SWOG remains fully committed to this Phase II
trial, which will yield valuable clinical data in this sizable yet poorly
treated patient group. Importantly, the trial will be conducted at minimal cost
to Oxford BioMedica with no loss of commercial rights.
TroVax Registration Strategy
The company's clinical priority for TroVax in 2005-06 is to commence at least
one pivotal trial of TroVax in the United States. Given the very encouraging
clinical data, both colorectal cancer and RCC are under consideration as the
lead indication. Oxford BioMedica plans to submit a formal request to the FDA in
the first half of 2005 for a pre-Phase III trial meeting. Following this
regulatory meeting and discussions with its clinical advisors, Oxford BioMedica
expects to finalise the protocol of the new trials by the middle of the year.
There is also the potential to apply for a Special Protocol Assessment (SPA)
from the FDA. This ensures that successful results can be used for a clinical
benefit claim in the registration submission. The company is targeting potential
approval of TroVax in 2008-09.
By advancing TroVax into pivotal trials, Oxford BioMedica hopes to enhance
substantially the value of the product, and thus improve the terms of potential
licensing deals. Assuming an appropriate level of efficacy, the approval and
launch of TroVax in the United States could be achieved through a single pivotal
trial. The initiation of a pivotal trial with an SPA maintains the company's
timelines for potential product registration.
Anti-5T4 Targeted Antibody Therapy
Oxford BioMedica's 5T4 technology and intellectual property include monoclonal
antibodies that bind to the 5T4 antigen. Wyeth, is developing a targeted
antibody therapy for the treatment of cancer using a humanised version of Oxford
BioMedica's anti-5T4 antibody linked to a cytotoxic molecule, calicheamicin.
A major problem with chemotherapy is the damage that the drugs cause to normal
tissues. The product from Oxford BioMedica and Wyeth is a 'magic bullet'
approach, which is designed to deliver the cytotoxic drug directly and
specifically to tumour cells, sparing healthy cells. Wyeth has pioneered
targeted antibody therapy through the launch of Mylotarg(R) for acute myeloid
leukaemia. A similar strategy is being applied in the collaboration with Oxford
BioMedica to develop a targeted therapy that could have application in all solid
tumours where the 5T4 antigen is present.
The collaboration with Wyeth has the potential to bring US$24 million to the
company in milestone payments, and significant royalties on product sales. Wyeth
has responsibility for and is funding the development of the product.
Wyeth confirmed its commitment to the programme at the end of 2003 by exercising
its option to license the rights to the anti-5T4 antibody following successful
technical evaluation of the product in preclinical studies. This triggered a
milestone payment. The product continues to meet Wyeth's high standards for
further development. During 2004, Wyeth commenced preparations for clinical
development, including process development, and clinical trials are under
consideration.
TroVax-Vet(R)
TroVax-Vet is a veterinary version of TroVax that uses a canine or feline
version of the 5T4 gene instead of the human form. Oxford BioMedica is
developing TroVax-Vet in collaboration with Intervet, which is a unit of Akzo
Nobel of Arnhem, the Netherlands, ranked among the top three in the global
animal health sector. Under the terms of the agreement, Intervet funds all
preclinical and clinical studies and Oxford BioMedica will receive development
milestones and royalties on sales.
During 2004, Intervet delivered on its objectives in the preclinical development
of TroVax-Vet for dogs. Studies in healthy animals were completed, demonstrating
that the product is safe, well tolerated and induces immune responses against
the canine 5T4 antigen. In 2005, Intervet expects to complete GMP manufacture of
the product and initiate pivotal preclinical safety studies. These data are
required to support a regulatory submission for clinical field trials.
MetXia(R)
MetXia is Oxford BioMedica's lead gene-based cancer therapeutic. The product
comprises a highly engineered retrovirus that delivers a specific human
cytochrome P450 gene to tumour cells. The enzyme encoded by the P450 gene
activates the commonly used cancer chemotherapy drug, cyclophosphamide (CPA), to
a form that destroys cells. MetXia converts the tumour into a 'drug factory',
enabling local production of the anti-tumour, cytotoxic derivative of CPA.
MetXia is potentially useful in the treatment of all solid tumours and their
metastases, particularly those where cyclophosphamide has proven efficacy.
The initial indication for the development of MetXia is the treatment of
pancreatic cancer through direct administration of both MetXia and CPA to the
tumour. Published data from trials with locally administered CPA and
encapsulated cells carrying the P450 enzyme have validated the concept of
treating pancreatic cancer with this approach. However, the use of encapsulated
cells is likely to be limited by manufacturing constraints. MetXia uses Oxford
BioMedica's gene therapy technology to deliver the P450 gene efficiently to
pancreatic tumour cells.
In April 2004, Oxford BioMedica reported that recruitment started in a UK Phase
I trial rolling into a Phase II trial of MetXia in patients with pancreatic
cancer. Recruitment has been slower than expected in the initial Phase I
(safety) stage of the trial owing to the restrictive criteria for patient
enrolment. The objective is to recruit six patients in the safety stage and a
further 21 patients in the Phase II (efficacy) stage. Oxford BioMedica is in
discussions with the UK regulatory authorities to broaden the criteria for
inclusion and, hence, accelerate patient recruitment. Additional clinical
centres are also being opened, which should ensure that the efficacy stage of
the trial remains on track. The company expects to report safety data in the
first half of 2005 and preliminary efficacy data before the end of 2005 with
final results in 2006.
The company intends to utilise data from the current trial in its discussions
with the regulatory authorities to determine the most expeditious route to
obtain approval of MetXia. The company has preliminary plans for a pivotal trial
in pancreatic cancer to start in 2006-07, subject to successful completion of
the current trial. In September 2004, the company strengthened its intellectual
property for MetXia by extending its license agreement with Massachusetts
General Hospital, Boston University and Dana-Faber Cancer Institute for the P450
gene to include pancreatic cancer.
As the programme progresses, Oxford BioMedica is seeking suitable partners for
the ongoing development and commercialisation of MetXia.
MetXia's mechanism may be relevant in a number of malignant tumours, including
breast cancer, prostate cancer and glioma (brain cancer). The two successful
proof of principle trials, completed in 2003, were primarily in late stage
breast cancer patients. Oxford BioMedica is considering breast cancer and other
cancer types for further trials with MetXia, which could be pursued with a
partner.
Neurotherapy
Oxford BioMedica is developing gene-based products for a range of neurological
conditions. These include programmes targeting neurodegenerative disorders such
as Parkinson's disease and motor neuron disease; neuro-ophthalmologic conditions
such as age-related macular degeneration and diabetic retinopathy; and also
nerve regeneration for spinal cord and related injuries.
All of the Company's neurotherapy products are based on the proprietary
LentiVector delivery technology. Oxford BioMedica's LentiVector technology is
one of the most powerful systems for safe and effective delivery of genes to the
brain, eyes and nervous system. The company has five LentiVector-based
neurotherapy products in advanced preclinical development. A regulatory
submission for clinical trials is being prepared for the lead product for
Parkinson's disease, and preclinical optimisation and clinical planning are
ongoing for the other programmes. Oxford BioMedica has set an objective of
initiating clinical trials with at least one product per year from the
neurotherapy pipeline starting in 2006.
ProSavin(R)
The company's lead neurotherapy product, ProSavin, is an innovative approach to
the treatment of Parkinson's disease. In Parkinson's disease, nerve cells in the
part of the brain that produces dopamine, the substantia nigra, decrease in
number due to slow progressive cell death. This causes a decrease in the amount
of available dopamine, the modulator of movement control. ProSavin uses a
LentiVector system to deliver the genes required for dopamine synthesis to
neurons in the striatum of the brain, thus creating a new 'dopamine factory'.
Oxford BioMedica announced in early 2004 that clinical trials with ProSavin were
expected to start in 2005-06. This was due to an extension of product
optimisation that enabled higher dopamine levels to be produced per unit of
drug. The company has also faced challenges in process development, which have
now been addressed with the achievement of substantially higher yields in the
manufacture of clinical material. The company is aiming to complete its
regulatory submission for clinical trials in the second half of 2005.
Importantly, the infrastructure put in place by the company to take ProSavin
into clinical trials can be used for all of the LentiVector-based products in
the portfolio.
Oxford BioMedica presented preclinical efficacy data with ProSavin in an
industry standard in vivo model of Parkinson's disease at the American Society
for Gene Therapy meeting in June 2004. Further data were presented at the
prestigious Society for Neuroscience meeting in October 2004. In these studies,
treatment with ProSavin resulted in almost complete recovery of movement
behaviour, an extremely significant result compared to other treatments for
Parkinson's disease reported in the literature.
The company is conducting further preclinical toxicity and efficacy studies with
ProSavin, which will support the regulatory submission. Data from these studies
are expected later in 2005. The planned Phase I/II trial, to be conducted at the
John Radcliffe Hospital in Oxford, UK, in patients with late stage Parkinson's
disease, is expected to commence in the first half of 2006. Initial data from
the first patients are anticipated by the end of 2006.
RetinoStat(R)
RetinoStat is Oxford BioMedica's novel gene-based treatment for wet age-related
macular degeneration and diabetic retinopathy. The product uses a LentiVector
system to deliver genes to the retina, which block the formation of new blood
vessels that cause retinopathy. The company is evaluating two versions of
RetinoStat with the anti-angiogenesis genes, endostatin and angiostatin,
licensed from EntreMed of Rockville, Maryland, USA. These two biological
products have been investigated extensively in various trials. The published
data suggest that endostatin and angiostatin have very low toxicity, are well
tolerated long term, and can shut down aberrant blood vessel growth.
Macular degeneration is a retinal degenerative disease that causes progressive
loss of central vision. The risk of developing macular degeneration increases
with age. Macular degeneration is the most common cause of vision loss in
individuals over the age of 55. Wet age-related macular degeneration (AMD)
accounts for about ten per cent of cases, but is responsible for 90 per cent of
severe vision loss.
During 2004, Oxford BioMedica demonstrated preclinical efficacy with two
configurations of RetinoStat in industry standard in vivo models of wet AMD. The
studies were conducted at the Institute of Ophthalmology in London, UK, and at
the Johns Hopkins Hospital in Baltimore, USA, with financial support from the US
charity, Foundation Fighting Blindness.
In 2005, the company expects to complete pivotal preclinical efficacy and dose
ranging studies, and optimisation of the RetinoStat configuration for clinical
trials. The results from these studies will be published and presented at
relevant conferences, including the prestigious American Association for
Research in Vision and Ophthalmology meeting in May in Fort Lauderdale, Florida,
USA. The company's objective is to initiate clinical trials with RetinoStat in
wet AMD in 2006-07.
MoNuDin(R)
Through modifications to the LentiVector system, Oxford BioMedica has developed
a technology for delivering genes to motor neurons indirectly by injecting the
product into muscle groups. Injection into a particular muscle efficiently
targets the motor neurons that control that muscle. MoNuDin is based on this
modified LentiVector technology, carrying the gene for the neuroprotective
protein, vascular endothelial growth factor. The product is being investigated
for the treatment of amyotrophic lateral sclerosis (ALS), the most common form
of motor neuron disease.
ALS, often referred to as Lou Gehrig's disease, is a progressive
neurodegenerative disease that affects nerve cells in the brain and the spinal
cord. Motor neurons reach from the brain to the spinal cord and from the spinal
cord to the muscles throughout the body. The progressive degeneration of the
motor neurons in ALS eventually leads to their death. When the motor neurons
die, the ability of the brain to initiate and control muscle movement is lost.
With voluntary muscle action progressively affected, patients in the later
stages of the disease may become totally paralysed.
Preclinical in vivo efficacy data with MoNuDin in an industry standard model of
ALS were published in Nature in May 2004, and were also presented at the Society
for Neuroscience meeting in October 2004. The studies showed that both the onset
and progression of disease were slowed and life expectancy was extended by 30
per cent with MoNuDin treatment. The results suggest that MoNuDin is one of the
most effective potential therapies in the field to date. The MoNuDin programme
has attracted funding from the US ALS Association via the company's
collaboration with the leading ALS expert, Dr. Nicholas Boulis at the Cleveland
Clinic Foundation in Cleveland, Ohio, USA.
The company is currently in discussion with the UK Motor Neurone Disease
Association, with regard to additional financial support for the programme. This
national organisation, dedicated to the support of patients with the disease,
may provide funding for initial clinical trials of MoNuDin. Oxford BioMedica
plans to conduct additional preclinical toxicology and efficacy studies during
2005, designed to support a regulatory submission for the start of clinical
trials with MoNuDin.
SMN-1G
In addition to the ALS programme, Oxford BioMedica is developing a gene-based
therapeutic to treat another motor neuron disease, spinal muscular atrophy
(SMA). SMA is one of the most common inherited causes of death in childhood and
is, as yet, incurable. It is caused by a mutation in the SMN1 gene that produces
a protein in the body called survival motor neuron (SMN) protein. Deficiency of
this protein has a severe affect on motor neurons and leads to muscle deficiency
throughout the body. Oxford BioMedica's SMN-1G product is designed to restore
SMN protein levels by delivering the corrected version of the SMN1 gene, using a
modified LentiVector system to reach motor neurons.
In December 2004, preclinical efficacy results with SMN-1G were published in the
Journal of Clinical Investigation. The preclinical studies were supported by
FightSMA, a US charitable organisation, in collaboration with Dr. Arthur Burghes
of The Ohio State University, a leading authority on SMA. In these studies, mice
with a defective SMN gene were given intramuscular injections with either SMN-1G
or a control. The mice treated with SMN-1G showed a statistically significant
improvement in survival, together with improved motor neuron survival. The
company aims to conduct further preclinical optimisation of SMN-1G during 2005
and preliminary planning for clinical development.
Innurex(R)
Innurex is Oxford BioMedica's gene-based product for nerve regeneration for the
treatment of spinal cord and related injuries. Again, based on the LentiVector
technology, the product carries the gene for a subtype of the retinoic acid
receptor (RARBeta2) that induces nerve cells to regrow by a process known as
'sprouting'.
Within the field of neurobiology nerve repair has been a long sought goal for
the treatment of nerve damage and spinal injury. The objective is to develop
treatments that induce nerve cells to regrow and bridge sites of injury, thereby
reconnecting the nerve fibres and restoring function.
During 2004, Oxford BioMedica made demonstrable progress in its Innurex
programme. Key preclinical data were presented in June 2004 at the American
Society for Gene Therapy meeting, and in October at the Society for Neuroscience
meeting. In these presentations, Oxford BioMedica scientists showed that Innurex
restores function to damaged limbs in a preclinical model of avulsion or stretch
injury. These results indicate that Innurex may benefit patients with nerve
damage resulting from severe pull or stretch injury, a common consequence of
sporting and motor accidents. Further preclinical studies and clinical planning
are underway and more data are expected in 2005.
The company's collaborator on Innurex, King's College London, was awarded a
grant of US$150,000 for the programme in April 2004 from the Christopher Reeve
Paralysis Foundation. This grant supports studies to explore the use of Innurex
in spinal cord injury.
Research Programmes
The vast majority of Oxford BioMedica's resources go to support the development
of its seven core products. However, the company has been opportunistic in
pursuing projects that might deliver considerable value for only modest
investment or where external agencies are prepared to meet the costs of the new
opportunity.
In March 2004, the UK Department of Health awarded the company a grant of £0.5
million to develop novel treatments for single gene disorders. The focus of the
grant is on the blood clotting disorder, haemophilia A, which is caused by a
defective Factor VIII gene. Oxford BioMedica has developed a product, named
Requinate(R), which carries a corrected version of the Factor VIII gene in a
LentiVector system. The Department of Health's contribution will enable the
company to progress the programme without compromising progress of the cancer
and neurotherapy products. Preclinical studies with Requinate have started, and
initial data are encouraging.
In August 2004, Oxford BioMedica scientists presented data at the American
Society for Neurochemistry conference showing that a LentiVector-based product
delivering short interfering RNA (siRNA) can dramatically slow down the
development of symptoms and increase life expectancy in a preclinical model of
an inherited neurodegenerative disease. These results were published in the
journal, Nature Medicine, in March 2005. While the company believes that this
particular project would not lead to a commercial product, it does provide proof
of principle for the use of the LentiVector system in the expanding field of RNA
interference (RNAi), with applications in disease modelling, drug discovery and
RNAi-based therapies. The delivery of siRNA with the LentiVector technology is
potentially applicable in any disease where it is important to suppress gene
activity, including, for example, cancer and AIDS.
Oxford BioMedica's research collaboration with ARIUS Research of Toronto,
Canada, to discover and characterise novel cancer targets, reached a key
milestone in October 2004. The companies also agreed to move to the next phase
of their collaboration. Under the agreement, tumour antigen targets and
antibodies can be out-licensed to commercial partners or developed by one or
both of the companies. In the initial phase of the collaboration, which began in
July 2002, 50 functional anti-cancer antibodies from the ARIUS library were used
by Oxford BioMedica to look for novel targets using proprietary technologies
from its gene discovery and immunotherapy programmes. The milestone achievement
related to the successful identification of three targets that offer
opportunities in a range of cancer diseases. The extended collaboration will
focus on one novel target that is over-expressed in gastrointestinal and other
cancers and is related to cancer metastasis.
Technology Licensing
In 2004, Oxford BioMedica established an active licensing programme for its
suite of gene delivery technologies to facilitate third party access and to
leverage the broad potential of these systems. This strategy is generating
sustainable revenue. Four licensing agreements were secured in 2004, and a
further agreement has been signed since the year end.
In addition to its application in gene-based therapeutic products, Oxford
BioMedica's LentiVector technology is an effective tool for genomics-based
target validation, drug screening, production systems and the creation of
transgenic animals. On 5 February 2004, the company signed an agreement with
Merck & Co of Whitehouse Station, New Jersey, USA, granting non-exclusive
worldwide rights to the LentiVector technology for research activities. Similar
licensing deals were signed with Biogen Idec of Cambridge, Massachusetts, USA,
on 23 December 2004; and with another leading biopharmaceutical company on 1
February 2005. Under the terms of these agreements, Oxford BioMedica receives
upfront licence payments and annual maintenance fees.
On 5 July 2004, a LentiVector license agreement was signed with Viragen of
Plantation, Florida, USA, for use of the technology in the development of avian
transgenics for efficient and economical manufacturing of therapeutic proteins
in chicken eggs. The Viragen agreement includes upfront and annual licence
payments in addition to milestone payments on the achievement of technical goals
and royalties on commercialisation.
These agreements confirm the broad utility of the LentiVector technology. Oxford
BioMedica expects the technology to become the system of choice for safe and
effective gene delivery in drug discovery and transgenics. Further LentiVector
licensing deals are anticipated in 2005 and there are currently five term sheets
under discussion.
In 2004, Oxford BioMedica granted the first licence to its retroviral ex vivo
gene delivery technology. The agreement with MolMed of Milan, Italy, was
announced on 13 December 2004. The agreement provides MolMed with rights to
utilise this technology in the development of MolMed's product pipeline. Oxford
BioMedica received an upfront licence fee and is entitled to annual maintenance
payments, together with potential clinical and regulatory milestone payments and
product royalties. The retroviral ex vivo gene delivery technology combines
Oxford BioMedica's technology together with some of the gene therapy technology
acquired from Chiron Corporation in June 2004.
Intellectual Property
Oxford BioMedica has an extensive estate of approximately 80 patent families,
which protect its pipeline of development candidates and suite of gene delivery
technologies. In 2004, two new patents were filed, together with seven US
continuation applications, which consolidate the portfolio. Seven patents were
granted in the period.
Oxford BioMedica has a comprehensive portfolio of US and European patents
covering the LentiVector technology, supporting the LentiVector-based pipeline
and its technology licensing activities. The patents include broad composition
of matter claims and methods of production claims for lentiviral vector gene
delivery systems of both human and non-human origin. The Oxford BioMedica team
was the first to construct lentiviral vectors that contain no viral genes at
all, and which comprise the minimum number of viral components in the viral
particles. It is this minimisation of the vectors that is the subject of these
patents. This work was done using vectors based on HIV and Equine Infectious
Anaemia Virus (EIAV), a horse virus that is not linked to any disease in humans.
In June 2004, Oxford BioMedica acquired a number of patent families from Chiron
Corporation's gene therapy patent portfolio that complement the company's
existing intellectual property. Separately, Chiron made an equity investment in
Oxford BioMedica and holds about 0.1 per cent of the company's shares.
Corporate Developments
Since the year end, on 19 January 2005, Oxford BioMedica announced that it had
received an approach from a third party regarding a potential merger. The Board
of Oxford BioMedica announced on 7 February that the discussions that followed
this unsolicited approach had terminated.
On 3 March 2005, Nick Woolf was promoted to the Board as an executive director.
He will maintain his title of Senior Vice President for Corporate Strategy. His
primary responsibilities include corporate finance, M&A evaluation and corporate
communications as well as an important role, jointly with Peter Nolan, in
business development and deal negotiation.
Conclusion
Since its inception in 1996, Oxford BioMedica has been dedicated to research and
development of novel gene-based medicines, which are both safe and effective for
the treatment of unmet medical needs. The progress made during 2004 in product
development has taken the company to a new level of maturity. Results from the
TroVax clinical programme continue to show highly encouraging evidence of safety
and efficacy. The company has also made progress towards the start of clinical
trials of its first LentiVector-based product, ProSavin for Parkinson's disease.
During 2005, the company expects to reach further important milestones in its
lead programmes, which will bring these products closer to commercialisation and
expand its licensing and collaboration opportunities.
For its most advanced product, TroVax, Oxford BioMedica expects to report
further Phase II trial results, and is planning pivotal trials to support
potential product registration. The second clinical candidate, MetXia, is
expected to deliver safety and preliminary efficacy results from the Phase I
trial rolling into a Phase II trial in pancreatic cancer during 2005.
For the LentiVector-based products, the company expects to complete the
regulatory submissions for the start of clinical trials with ProSavin; and to
advance the pipeline such that one additional product candidate could enter
clinical development each year. In terms of collaborations and licensing,
discussions continue with potential partners for the lead products and further
licensing agreements are expected for the LentiVector technology.
The company's corporate strategy remains focused on the development of its core
oncology and neurotherapy portfolio of novel gene-based medicines, while
enhancing value and reducing risk through collaborations and licensing. On
behalf of the Board, we want to thank our shareholders, partners and dedicated
staff for their ongoing support and commitment.
Dr Peter Johnson Professor Alan Kingsman
Chairman Chief executive officer
Financial Review
Oxford BioMedica reported a reduction in its loss before tax in 2004, which was
better than anticipated, and within budget. The lower loss reflects higher
revenue from technology licensing and continued tight control over spending. The
restructuring of US operations and rationalisation of discovery research,
announced in 2003, was completed in early 2004. Expenditure has been focused on
the lead development programmes in oncology and neurotherapy, particularly the
expanded clinical trials programme for TroVax and the scale-up of manufacture
for both TroVax and ProSavin. The group headcount increased to 66 employees at
31 December 2004 from 61 at the end of 2003. This increase relates, primarily,
to additional operational requirements in manufacturing and clinical
development.
Fees from four technology licensing deals, that were signed during the year with
Merck & Co, Viragen, MolMed and Biogen Idec respectively, bolstered revenue in
2004. These agreements are expected to generate recurring revenue from annual
maintenance payments and, in the case of Viragen and MolMed, there is the
potential for additional income and royalties on commercialisation. Since the
year end, on 1 February 2005, a further research license with a leading
biopharmaceutical company was secured for the LentiVector technology.
The cash outflow for 2004 was essentially static from the previous year at £9.7
million (2003: £9.6 million), and cash and short term investments at 31 December
2004 were £22.4 million compared to £31.8 million at the end of 2003. The
company anticipates that current cash resources are sufficient to support the
development activities into 2007, before taking account of additional income
from potential new collaborations and licensing agreements.
Revenue
The company reported an increase in revenue of 34 per cent to £0.5 million for
the year ended 31 December 2004 (2003: £0.4 million). Although the absolute
figure is not substantial relative to the company's cost base, it reflects a
growing and sustainable income stream from technology licensing. Reported
revenue included the initial payment under the agreement with Viragen, and a
proportion of the first-year payments from Merck & Co, MolMed and Biogen Idec.
Operating Expenses and Income
Operating expenses in 2004 were essentially unchanged at £13.5 million (2003:
£13.7 million). As in previous years, operating expenses were largely related
to research and development, where the mix continues to shift towards late stage
preclinical and clinical development. Research and development expenses were
lower at £9.2 million (2003: £10.8 million). UK research and development costs
were £0.4 million higher than last year, due to increased investment in process
development, but as a result of restructuring savings, US research and
development costs were £2.0 million lower. Administration costs in 2004,
excluding exceptional expenses, were £2.8 million (2003: £2.9 million).
Included in operating expenses was an exceptional charge of £1.6 million (2003:
nil). This was related to restructuring the US operations, comprising headcount
reduction and relocation to smaller premises in San Diego. The reorganisation
was completed in early 2004 and has resulted in an estimated annual cost saving
in excess of £1 million. The cash outflow attributable to the exceptional item
in 2004, net of the proceeds of sale of fixed assets, was £0.4 million.
Operating income from grants in 2004 was lower than the previous year at £0.4
million. Grant income of £0.7 million in 2003 included arrears from 2002 for two
grant programmes.
Operating Results
Before the exceptional item, the operating loss in 2004 narrowed to £11.1
million (2003: £12.7 million). After the exceptional item, the operating loss
was the same as the previous year at £12.7 million.
Interest
Net interest receivable was £1.2 million in 2004 (2003: £0.7 million). The
increase was a result of higher average cash and short term investment balances
during the year, together with better rates of interest. The average return on
cash balances throughout the year increased to 4.4 per cent in 2004 from 3.6 per
cent in 2003.
Results Before Tax
The loss before tax in 2004 narrowed to £11.5 million (2003: £11.9 million).
This position was consistent with the increased technology licensing revenue,
the restructuring savings and the focus of expenditure on the lead development
programmes during 2004.
Taxation
Taxation for 2004 amounted to a credit of £0.9 million. The figure comprises,
principally, the UK research and development tax credit, which was £1.0 million
in 2004, less an adjustment to previous years' claims of £0.1 million (2003 tax
credit: £1.2 million). This credit is an incentive designed to support the
group's investment in product and technology development.
Liquidity and Capital Resources
Cash and short term investments at 31 December 2004 were £22.4 million (2003:
£31.8 million). The net cash outflow before management of liquid resources and
financing in 2004 was essentially static from the previous year at £9.7 million
(2003: £9.6 million).
The fixed asset base at the end of 2004 was lower at £1.3 million (2003: £2.5
million), owing largely to the disposal of laboratory equipment and write-down
of other assets at the US facility as part of the restructuring. Debtors
increased to £3.3 million (2003: £2.4 million), of which £1.7 million (2003:
£1.2 million) was research and development tax credit. Creditors of £1.7 million
(2003: £1.5 million) comprised principally accruals and deferred income.
Issue of Shares
A total of 1.8 million shares were issued in 2004, raising £0.3 million. 1.1
million shares were issued on the exercise of share options, and 0.7 million
shares were issued in connection with the acquisition of patent rights.
Financial Outlook
The company's financial position remains strong with year end cash and short
term investments of £22.4 million. Internal financial projections, before taking
account of revenue from new product licensing agreements, indicate that by
maintaining tight control on expenditure, current cash resources should be
sufficient until 2007.
Andrew Wood
Chief financial officer
Consolidated Profit and Loss Account
for the year ended 31 December 2004
Notes 2004 2003
£'000 £'000
Turnover 2 502 374
Research and development costs (9,190) (10,773)
Administrative expenses (2,760) (2,922)
Exceptional administrative expenses 3 (1,568) -
Total administrative expenses (4,328) (2,922)
Operating expenses (13,518) (13,695)
Other operating income: government and other grants 364 669
receivable
Net operating expenses (13,154) (13,026)
Loss before interest and exceptional item (11,084) (12,652)
Exceptional item (1,568) -
Operating loss (12,652) (12,652)
Interest and similar items 1,158 711
Loss on ordinary activities before taxation 2 (11,494) (11,941)
Tax credit on loss on ordinary activities 4 884 1,203
Loss for the year (10,610) (10,738)
Basic loss and diluted loss per ordinary share 5 (2.9p) (3.9p)
The results for the years above are derived entirely from continuing operations.
There is no difference between the loss on ordinary activities before taxation
and the loss for the years stated above, and their historical cost equivalents.
Statement of Group Total Recognised Gains and Losses
Note 2004 2003
£'000 £'000
Loss for the financial year (10,610) (10,738)
Currency translation differences on foreign currency 10 (47) (179)
net investments
Total recognised losses for the year (10,657) (10,917)
Consolidated Balance Sheet
at 31 December 2004
Notes 2004 2003
£'000 £'000
Fixed assets
Intangible assets 86 135
Tangible assets 6 1,237 2,331
Investments - 26
1,323 2,492
Current assets
Debtors 7 3,303 2,386
Investments 22,377 31,700
Cash at bank and in hand 40 136
25,720 34,222
Creditors: amounts falling due 8 (1,741) (1,501)
within one year
Net current assets/(liabilities) 23,979 32,721
Total assets less current 25,302 35,213
liabilities
Provisions for liabilities and 9 (464) -
charges
Net assets 24,838 35,213
Capital and reserves
Called-up share capital 3,721 3,703
Share premium account 78,309 78,045
Other reserve 711 711
Profit and loss account (deficit) (57,903) (47,246)
Equity shareholders' funds 10 24,838 35,213
Consolidated Cash Flow Statement
for the year ended 31 December 2004
Notes 2004 2003
£'000 £'000
Operating activities
Net cash outflow from continuing operating activities
(reconciliation to operating loss below) (10,976) (11,488)
Returns on investments and servicing of finance
Interest received 1,096 638
Taxation
UK R&D tax credit received 400 1,259
Overseas tax received - 8
400 1,267
Capital expenditure
Purchase of tangible fixed assets (316) (51)
Sale of tangible fixed assets 110 -
(206) (51)
Net cash outflow before management of liquid resources and (9,686) (9,634)
financing
Management of liquid resources
Transfer to deposit accounts (1,624) (12,368)
Transfer to current accounts 10,947 1,329
9,323 (11,039)
Financing
Issue of ordinary shares 301 22,215
Expenses of share issue (20) (1,695)
Net cash inflow from financing 281 20,520
(Decrease)/increase in cash in the year (82) (153)
Reconciliation of Operating Loss to Net Cash Outflow from Operating Activities
2004 2003
£'000 £'000
Continuing activities
Operating loss (12,652) (12,652)
Amortisation of intangible fixed assets 49 50
Depreciation of tangible fixed assets 1,040 943
Loss on disposal of fixed assets 260 71
Provision for impairment of fixed asset investments 26 -
Non-cash consideration for acquired intellectual property rights - 79
Decrease in debtors due after more than one year 32 -
Increase in trade debtors (162)
Increase in other debtors and other tax receivable (203) (232)
Increase in prepayments and accrued income (61) (18)
Increase/(decrease) in trade creditors 20 (74)
Increase in other taxation and social security 24 31
Increase in accruals and deferred income 181 360
Onerous lease provision 464 -
Exchange rate differences 6 (46)
Net cash outflow from continuing operating activities (10,976) (11,488)
Notes to the accounts
for the year ended 31 December 2004
1 Basis of preparation
The figures and financial information for the years ended 31 December 2004 and
31 December 2003 do not constitute the statutory financial statements for the
respective years. Financial statements for the year ended 31 December 2003 have
been delivered to the Registrar of Companies and included the auditors' report.
Financial statements for the year ended 31 December 2004 have not yet been
delivered to the Registrar. The auditors' reports on the financial statements
for the years ended 31 December 2004 and 31 December 2003 were unqualified and
did not contain statements under either section 237 (2) or section 237 (3) of
the Companies Act 1985.
Copies of this announcement are available from the Company Secretary. The
audited statutory financial statements for the year ended 31 December 2003 are
expected to be distributed to shareholders by 11 April 2005 and will be
available at the registered office of the Company, Medawar Centre, Oxford
Science Park, Oxford, OX4 4GA.
This announcement was approved by the Board of Oxford BioMedica plc on 18 March
2005.
Turnover and loss on ordinary activities before taxation
The group's turnover and loss on ordinary activities before taxation are derived
entirely from its principal activity. The group's principal operating location
is in the United Kingdom, but there is also an operating unit in the United
States of America.
Turnover 2004 2003
Geographical analysis Turnover Turnover Turnover Turnover
by by by by
destination origin destination origin
£'000 £'000 £'000 £'000
United Kingdom 35 502 29 374
Rest of Europe 57 - - -
North America 410 - 345 -
502 502 374 374
Loss on ordinary activities before taxation 2004 2004 2003
Geographical analysis After Before
exceptional exceptional
item item
£'000 £'000 £'000
United Kingdom 8,906 8,886 8,693
Rest of Europe - - -
North America 2,588 1,040 3,248
11,494 9,926 11,941
Net assets 2004 2003
Geographical analysis £'000 £'000
United Kingdom 2,689 2,216
Rest of Europe - -
North America (268) 1,161
Net operating assets 2,421 3,377
Investments and cash at bank and in hand 22,417 31,836
24,838 35,213
3 Exceptional item: reorganisation of US activities
In January 2004, following a review of operations and resources, the group
closed its US process development and manufacturing unit. A business development
and intellectual property management capability has been retained, and the US
subsidiary has sublet its leasehold facility and relocated to new premises.
Provision has been made for those reorganisation costs not yet incurred at 31
December 2004 (see note 16).
Exceptional costs of £1,568,000 included in the accounts for the year ended 31
December 2004 comprise £226,000 loss on disposal of fixed assets, £309,000 write
down of tangible fixed assets included in depreciation of fixed assets, £578,000
onerous lease charge, £227,000 severance payments and £228,000 other
reorganisation costs. The cash outflow attributable to the exceptional item in
the year ended 31 December 2004, net of the proceeds of sale of fixed assets,
was £407,000.
4 Tax credit on loss on ordinary activities
The group is entitled to claim tax credits in the United Kingdom for certain
research and development expenditure. The amount included in the financial
statements for the year ended 31 December 2004 represents the credit receivable
by the group for the year. These amounts have not yet been agreed with the
relevant tax authorities.
2004 2003
£'000 £'000
Current tax
United Kingdom corporation tax research and development credit (1,000) (1,200)
Overseas taxation 1 -
(999) (1,200)
Prior years' tax adjustments
United Kingdom corporation tax research and development credit 115 3
Overseas taxation - -
Total current tax net credit (884) (1,197)
Deferred tax
Reversal of timing differences: overseas tax - (6)
Total deferred tax (note17) - (6)
Tax credit on loss on ordinary activities (884) (1,203)
At 31 December 2004, the group had tax losses to be carried forward of
approximately £38.4 million (2003: £32.6 million) of which £18.7 million has
been agreed with the revenue authorities. Of the group tax losses, £38.4 million
(2003: £32.1 million) arose in the United Kingdom.
5 Basic loss and diluted loss per ordinary share
The basic loss per share has been calculated by dividing the loss for the year
by the weighted average number of shares of 371,457,455 in issue during the year
ended 31 December 2004 (2003: 273,876,723).
The company had no dilutive potential ordinary shares in either year which would
serve to increase the loss per ordinary share. There is therefore no difference
between the loss per ordinary share and the diluted loss per ordinary share.
6 Tangible fixed assets
Short Office Computer Laboratory Total
leasehold equipment, equipment equipment
improvements fixtures
and fittings
£'000 £'000 £'000 £'000 £'000
Cost
At 1 January 2004 2,238 231 325 2,871 5,665
Additions - 3 37 299 339
Disposals - (147) (53) (653) (853)
Exchange differences (25) (1) (1) (23) (50)
At 31 December 2004 2,213 86 308 2,494 5,101
Accumulated depreciation
At 1 January 2004 1,195 154 254 1,731 3,334
Charge for the year 591 22 61 366 1,040
Disposals - (117) (47) (319) (483)
Exchange differences (18) - (1) (8) (27)
At 31 December 2004 1,768 59 267 1,770 3,864
Net book amount at 445 27 41 724 1,237
31 December 2004
Net book amount at 1,043 77 71 1,140 2,331
31 December 2003
7 Debtors
2004 2003
£'000 £'000
Amounts falling due after more than one year
Other debtors - rent deposit 214 263
Amounts falling due within one year
Trade debtors 162 -
Other debtors 619 374
Corporation tax receivable 1,685 1,200
Other tax receivable 124 107
Prepayments and accrued income 499 442
3,089 2,123
Total debtors 3,303 2,386
8 Creditors: amounts falling due within one year
Company
2004 2003
£'000 £'000
Trade creditors 351 310
Other taxation and social security 219 195
Accruals and deferred income 1,171 996
1,741 1,501
9 Provision for liabilities and charges
Onerous lease
£'000
At 1 January 2004 -
Charged to the profit and loss account 568
Utilised in the year (101)
Amortisation of discount 13
Adjustment due to change in discount rate 10
Exchange differences (26)
At 31 December 2004 464
The onerous lease provision relates to the estimated rental shortfall in respect
of the property in San Diego, USA, discounted at 4.55% per annum, and will be
utilised over the term of the lease which is due to expire in 2012.
10 Reconciliation of movements in group shareholders' funds
2004 2003
£'000 £'000
Loss for the year (10,610) (10,738)
New share capital issued 301 22,294
Expenses of share issue (19) (1,696)
Exchange differences (47) (179)
Net (reduction in)/addition to shareholders' funds (10,375) 9,681
Opening shareholders' funds 35,213 25,532
Closing shareholders' funds 24,838 35,213
--------------------------
* Clinical response data from Oxford BioMedica's Phase II trials are unaudited.
They are based on patients that are evaluable and use the industry standard
Response Evaluation Criteria in Solid Tumours (RECIST). The data from the trials
of the chemotherapy agents alone, cited in this report, are derived from
evaluable patients, using clinical response criteria set by the World Health
Organisation (WHO). The criteria defined by RECIST and WHO are similar but not
identical.
This information is provided by RNS
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