Final Results - Year Ended 31 December 1999
Proteome Sciences PLC
28 March 2000
Proteome Sciences plc
Preliminary Announcement of Financial Results for the year ended
31 December 1999
Chairman's Report
Proteome Sciences continues to pursue a focused proteomics
research programme to identify changes in protein expression in
specific disease states and the usage of such protein markers for
diagnostic purposes and as novel molecular targets for drug
discovery, principally in the areas of neurological disorders,
cancer, chronic heart disease, rejection after solid organ
transplantation, diabetes and obesity.
In the US, Intronn LLC, the 50 per cent. owned US subsidiary, has
developed a proprietary method of gene based therapy. The lead
technology, spliceosome mediated RNA trans-splicing (SMaRTT), has
a broad spectrum of potential applications ranging from gene
therapy for inherited genetic disorders, cancer, and repair of
genetic mutations (such as those causing cystic fibrosis), to
address the modification of gene expression in plants. At the
same time, Intronn has developed some 'tool box' technologies as
spin offs from the main SMaRTT programme, including exon tagging,
quality control and standardisation markers and oligonucleotide
purification.
Proteome Sciences proposes to commercialise the results of the
research through sub-licensing their use to pharmaceutical,
diagnostics, genomics and gene therapy companies. Proteome
Sciences expects to generate substantially all its future revenue
in this way.
Review of Activities
Over the last year, I am very pleased to report that proteomics
appears to have arrived on centre stage in the field of drug
discovery and development, as one of the key techniques necessary
to unlock functional genomics. This is particularly significant,
given the impending completion of the sequencing of the human
genome, and the emphasis now being placed on bridging the gap
between an identified gene mutation and a disease condition by
looking at subtle qualitative and or quantitative changes in
protein expression. By identifying changes in protein expression
in disease, proteomics can be utilised to assist in the
identification of the same disease association with the gene.
By comparing control and disease samples, it is possible to
identify over and under expression of proteins in disease and
their post-translational modification. These proteins may be
targets for drug development or molecular markers of disease
playing a role in diagnostic and prognostic monitoring of disease
progression.
In parallel, gene therapy, the second platform technology in
which Proteome Sciences is involved through Intronn LLC is
attracting considerable interest and corporate activity both in
the US and Europe.
The US Patent Office has recently allowed a patent to Oxford
Biomedica plc, covering broad aspects of the delivery for
retroviral and lentiviral vector systems, which can be used in
gene therapy products for a wide range of diseases. In October
1999 Intronn entered into a Material Transfer Agreement ('MTA')
with Oxford Biomedica plc in respect of PTMs. This should provide
Intronn with an opportunity to exploit the commercial
opportunities for its pre-therapeutic RNA molecules (PTMs), by
using a wide range of vector delivery systems developed by third
parties.
PTMs function by base-pairing with a unique (disease associated)
pre-mRNA, blocking cis-splicing of the target pre-mRNA and
promoting a spliceosome mediated trans-splicing reaction (SMaRTT)
to occur between an exon in the PTM and the target pre-mRNA. At
the same time, considerable international media attention and
debate has centred around genetic modification of plants/crops
and developments within agricultural biotechnology.
Proteomic Research programme
The projects undertaken through the primary collaborative
agreements are concentrated in diabetes and obesity, cancer,
neurological disease, rejection after solid organ transplantation
and chronic heart disease.
Diabetes and Obesity
At the time of the interim results, Proteome Sciences reported
that a group of three patent applications had been filed from the
research being undertaken at the University of Geneva and the
University of Buckingham. This research related to the proteomic
approach being used to identify new molecular targets for
pancreatic islet cell function, insulin resistance and obesity.
The identification of these proteins has now been completed and
further progress with this approach has led to the filing of two
more patent applications. The company has entered into
Confidential Disclosure Agreements with ten different parties
with the intention of establishing a funded research programme
for the continuation of this research. This process is being
actively pursued and further developments are anticipated during
the year.
The Company's researchers presented new data to 600 delegates at
the Keystone Symposium on Diabetes Mellitus: Molecular Mutations,
Genetics and Prospect for New Therapy held on 16-22 February 2000
in Taos, New Mexico, USA, which attracted considerable interest
with an experimental paradigm for identifying new molecular
targets associated with insulin resistance. By treating normal
and insulin resistant mice with the insulin sensitiser drug
rosiglitazone, it was possible to identify over 48 proteins that
were differentially expressed between normal and insulin
resistant mice and which were also modulated by rosiglitazone in
the course of inducing insulin sensitivity in the insulin
resistant mice. These proteins are potential molecular targets
for the treatment of non-insulin dependent diabetes.
Cancer
The current phase of the research programme at the University of
Michigan was concluded at the end of November. The programme has
proved highly successful, resulting in patent applications being
filed for protein markers for lung, oesophageal, colon and breast
cancer, in addition to patent applications relating to
proprietary methodologies and techniques. A further patent
application was filed in August 1999 for the usage of proteins in
the identification and treatment of lung cancer.
The University of Michigan was awarded a $10m grant in October by
the NIH for proteomic research in oncology to use these proteomic
techniques in an integrated genomic approach for DNA and protein
analysis and for the molecular analysis of tumours. A special
feature of the programme will be the integration of gene
expression analysis at both the RNA and protein levels. Proteome
Sciences has exercised an option for an exclusive licence to
commercialise the results and continues to seek partners to take
the programme on to the next stage.
Neurological
The main emphasis of this research, principally undertaken at the
University Cantonal Hospital Geneva, is to identify novel
diagnostic and therapeutic targets for a range of neurological
disorders including brain damage, stroke, Parkinson's disease,
pain and transmissible spongiform encephalopathies (BSE, scrapie,
CJD, nvCJD).
A proprietary human astrocyte cell line 2D PAGE reference map was
established in 1995 for comparison with numerous tissue biopsies,
cells and body fluids. A substantial collection of sequential
samples from acute stroke patients was collected and the
potential marker candidates identified have resulted in a patent
application being filed in December 1999 for a diagnostic assay
for stroke from a blood sample. The ongoing work programme has
provided rapid progress with very interesting results.
There continues to be considerable media attention as to the
potential risk of substantial numbers of possible CJD/nvCJD
victims emerging in the future. Proteome Sciences has maintained
its involvement in the area and has focused its attention on
using highly sensitive techniques for the early identification of
the abnormal forms of the mutated prion protein PrP and to try
and identify such changes, preferably in an accessible body
fluid. Considerable progress has been made and a further patent
application has been filed for a new method of detection of CJD
and other forms of TSE. The present invention is for an assay of
high sensitivity, specificity and predictive accuracy for CJD
taken from a blood sample.
The research programme in Parkinson's, to establish a CSF
reference map and then to look at different protein expression,
has generated data on 34 protein changes of significance between
control and disease. These results are in the process of being
further analysed with a view to assessing their applicability for
patent protection.
Rejection after Solid Organ Transplantation/Chronic Heart Disease
The aim of the REMAP project is to identify diagnostic and/or
prognostic markers of acute organ rejection and to develop a
reliable, non-invasive way of detecting acute rejection following
solid organ transplantation. The proteomic approach adopted was
to identify, by 2DE analysis of sequential tissue biopsy samples,
changes in protein expression which either precede or occur
during periods of acute rejection.
Significant progress is being made with 20 protein spots
submitted for protein characterisation. ELISA assays can now
start to be developed to test their potential as non-invasive
markers of acute rejection using the serum samples collected from
the REMAP study patients.
The EUREKA grant, provided by the Department of Trade and
Industry, has not been fully drawn down and Proteome Sciences has
applied for an extension to the grant period.
A further patent application was filed in November 1999 in
relation to the work undertaken on the vimentin chronic rejection
marker. Considerable additional data has resulted from a 109
patient study, conducted over a five year period. This shows that
on at least one occasion 107 out of the 109 patients increased
their anti-vimentin antibody titres after transplantation.
Research into chronic heart disease under the two year funded
agreement with Rhone-Poulenc Rorer has made good progress, but
detailed results from the programme are not expected to emerge
until the end of 2000.
The Protein Separation and Analysis Service at Harefield
continues to carry out limited third party contracts.
Intronn
The last year has proved most successful for Intronn. In January,
results with SMaRTT technology were presented at the Keystone
Symposium, Salt Lake City which demonstrated for the first time
the repair of the genetic mutations in the mRNA which is
defective in cystic fibrosis, SMaRTT offers a major advantage
using vector systems by specifically restricting treatment to the
faulty fibrosis cells, thereby preventing other healthy cells
from being damaged.
In March, SMaRTT featured in the March edition of Nature
Biotechnology. The magazine press release reported a novel gene
therapy approach that exploited the cellular machinery for
editing RNA to correct faulty genes, a human protein engineered
to sabotage cancer cells, and a plant genetically engineered for
improved nutritive value. In a review of the article Professor
Ryszard Kole of the University of North Carolina said, in
principle, that the trans-splicing approach should be able to
modify any gene in any cell type.
Intronn was awarded a Phase 1 SBIR grant from the National
Institute of Health (NIH) in the USA for $235,000, more than
twice the level that had been requested. In August 1999,
notification was received of the issuance of Intronn's first main
US patent which covers the SMaRTT gene therapy platform.
Notification was received by Intronn in February 2000 from the
Cystic Fibrosis Foundation in the USA that it has been awarded a
grant for part of the cystic fibrosis programme.
At the time of the interim results in October, the Board was
evaluating the options available to maximise the value of
Proteome Sciences' interest in Intronn. The options contemplated
included a separate structure for the company with independent
funding and a possible future listing. Agreement has been reached
with Intronn Holdings LLC, the owners of the remaining 50 per
cent. of Intronn LLC, to simplify the ownership structure,
whereby Intronn LLC will be incorporated and the differing profit
participations will be exchanged for equity in the new company.
Under these arrangements, Proteome Sciences will be allotted 60
per cent. of the equity and Intronn Holdings 40 per cent. The
process to raise the appropriate funding for Intronn and the
search for a CEO with profile and expertise in gene therapy is
underway and further developments are expected in the first half
of the year. The main alternative technologies to SMaRTT centre
on ribozymes and antisense.
In November, Intronn entered into MTAs in respect of PTMs with
King's College, London and The General Hospital, Salzburg,
Austria, where Intronn's constructs will be tested for specific
neurological and dermatological applications.
On the basis of current interest, Intronn anticipates that it may
soon enter into a funded programme to determine the efficiency of
SMARTT technology to address the modification of gene expression
in plants with a major company. Such a project is expected to be
completed within twelve months. If satisfactory results are
achieved, the company will negotiate a collaborative licensing
and Research and Development agreement with Intronn with related
milestone and royalty payments.
Results
In the twelve month period ended 31 December 1999, Proteome
Sciences incurred a pre-tax loss of £1,229,758 (1998:
£1,850,527). A reversal of the realised foreign exchange loss of
the previous year and a reduction in the level of research and
development costs have been the main factors contributing to the
lower level of losses.
At the year end, cash balances stood at £446,818. As disclosed at
the time of the Interim Results in the second half of 1999,
Proteome Sciences implemented the contingency plan, referred to
in the 1998 Annual Report and Accounts which involved reductions
in overhead costs and the level of research expenditure.
Current Outlook
Whilst the potential of proteomics has been widely recognised for
a number of years, it was only in 1999 that it came of age, with
a handful of international collaborative research agreements
established in proteomics in the second half and early 2000 with
major pharmaceutical companies. Proteomics is not only an
important tool that complements the information provided by
genomics, potentially it also provides a more efficient method of
understanding disease mechanisms and a fast track to genes, as
well as drug targets.
Proteome Sciences has been using proteomics for proprietary
discovery since the early 1990s to identify protein changes in
disease. The company has concentrated on 'high output' rather
than 'high throughput', addressing quality of samples, separation
and sensitivity of detection, rather than volume and its focus on
direct discovery rather than third party contract research. This
was a strategic decision by the Board to position Proteome
Sciences in what it considered to be the optimal position to
realise long term shareholder value. A portfolio of over twenty
patents and patent applications has been established, largely
concentrated on changes in protein expression across the range of
diseases covered by the research programme.
Over the last two years, the Board has been frustrated with the
time required to commercialise the results of the research
programme with major pharmaceutical companies and to convert the
protein markers into licences and commercial revenue. As pointed
out earlier in my statement, it is only as we are moving through
2000 that the tide appears to be changing and that now there is
beginning to be a wider appreciation of the potential value of
Proteome Sciences' intellectual property and its position in
proteomics and gene therapy.
As indicated above, in order to conserve its financial position,
Proteome Sciences implemented reductions in overhead costs and
the level of research expenditure at the time of the Interim
Results in October 1999. The programmes at the University of
Michigan and the University Cantonal Hospital Geneva were
deferred at the end of November and December respectively, with
the diabetes/obesity programme at the University of Geneva and
the University of Buckingham and the arrangements at Harefield,
London continuing into 2000. In the interim statement, Proteome
Sciences stated that it intended to resume part or all of the
research programmes in the light of the market background, the
status of licensing arrangements, research partnerships and the
level of funding available.
Subject to completion of the proposed Placing and the Open Offer,
I am pleased to report that Proteome Sciences will have the
necessary funding to resume the full proteomic research
programmes with its main collaborative partners and to take the
research through to commercialisation.
With a new level of perception and acceptance of proteomics, the
Board feels that it is now appropriate to move the corporate
structure at Proteome Sciences to a less virtual basis and
subject to raising sufficient funds under the Open Offer is
proposing to establish its own small specialist proteomics
facility in the UK. In addition to the protein facilities based
at Harefield, this will provide a core research facility to
undertake partnership research programmes with pharmaceutical
companies and to accelerate the projects underway through the
collaborations with the HCUG, Harefield, London, the University
of Buckingham and the University of Geneva.
A senior business development manager has been appointed, with a
strong background in protein separation, mass spectrometry and
bioinformatics, to interface between the scientific researchers
and the corporate customers/prospective licensees and to
accelerate the commercialisation process.
The research projects in diabetes/obesity, stroke, TSE, CJD,
nvCJD and chronic heart disease/rejection, have all reached
exciting stages in their development and there should be an
interesting news flow through 2000 and 2001. The Directors intend
to pursue an active licensing and partnership programme to
exploit the Company's research.
The Board is particularly encouraged by the development of the
assay of high sensitivity, specificity and predictive accuracy
for CJD and the diagnostic assay for stroke, both taken from
blood samples. Everyone is at risk from stroke and there are at
least 350,000 people disabled by it at any one time in the UK and
it is the UK's third highest killer disease (source: The Stroke
Association).
The company is looking at various grant schemes in the UK and the
EEC to supplement the portfolio of Proteome Sciences' research
projects.
In the US, Intronn should benefit considerably from incorporation
and is looking to appoint a high profile CEO with a gene therapy
background, to take the company through its first major funding
round, expected to close in July.
In light of the buoyant activity in the biotechnology section in
2000, the Board will continue to evaluate the options available
to maximise the value of its interest in Intronn, in particular
in respect of external funding and the possibility of a listing
in the US.
On the basis of current interest, Intronn anticipates that it may
soon enter into a funded programme to determine the efficiency of
SMaRTT technology to address the modification of gene expression
in plants with a major company. Such a project is expected to be
completed within twelve months. If satisfactory results are
achieved, the company will negotiate a collaborative licensing
and Research and Development agreement with Intronn with related
milestone and royalty payments. Other opportunities for similar
agreements for SMaRTT applications will be actively pursued.
Intronn has several manuscripts which have been submitted for
review by scientific journals which should further substantiate
and extend the SMaRTT technology platform and its potential
applications. Results should flow through from the MTA agreements
already in place and a number of other agreements are anticipated
before the end of the year. After its successful Phase 1 SBIR
grant, Intronn is in the process of submitting a major
application for a Phase 2 SBIR grant. This should all combine to
provide an exciting backcloth for Intronn in 2000 and to help
establish a strong basis of valuation for the refinanced entity,
where Proteome Sciences will remain the principal shareholder.
In the last six months of 1999, there were increasing levels of
corporate and merger activity in the biotechnology sectors on
both sides of the Atlantic. At the time of publication of the
Interim Results in October, the Directors pointed out the
pressures for consolidation in the industry and the creation of
larger units of specialist focus and 'one stop solutions'.
Subject to completion of the Placing and the Open Offer, the
Directors consider that the funding requirements for Proteome
Sciences will be addressed for the foreseeable future. The Board
continues to investigate a range of options, including possible
merger, strategic alliances and other opportunities which could
enhance shareholder value.
Proteome Sciences has established a unique position in proteomics
and in gene therapy through SMaRTT technology. The Directors
believe that the Company is strongly placed to capitalise from
the two technology platforms and the Board looks forward to the
future with confidence and to the application and
commercialisation of the two technology platforms in functional
genomics.
As a closing comment, I would like to take this opportunity to
sincerely thank our employees, scientists, collaborators and
consultants for their hard work and commitment which have
contributed to the success of Proteome Sciences' research
programme.
R Stephen Harris
Chairman
Unaudited Consolidated profit and loss account
For the year ended 31st December 1999
Notes 1999 1998
£ £
Administration (761,396) (1,061,510)
expenses
Realised exchange 4 71,072 (22,246)
gains/(losses)
Research and (560,190) (904,707)
development
expenses
Other operating (5,614) (13,528)
expenses
-------- ---------
Operating loss (1,256,128) (2,001,991)
Interest 32,817 155,349
receivable
Interest payable 3 (6,447) (3,885)
and similar
charges
-------- ---------
Loss on ordinary 4 (1,229,758) (1,850,527)
activities before
taxation
Tax on loss on 7 - -
ordinary
activities
-------- ---------
Loss for the 16 (1,229,758) (1,850,527)
financial year
======== =========
Loss per share
Basic and diluted 8 1.57p 2.38p
======== =========
Notes to the Financial Information.
1.There has been no change to any of the accounting policies set
out in the 1998 statutory accounts.
2. Following the loss of £1,229,758 incurred in the period, the
Directors do not recommend the payment of a dividend.
3.(a) The calculation of the loss per share for the year ended 31
December 1999 is based on the loss of the financial period of
£1,229,758 and on 78,505,304 Ordinary Shares, being the weighted
average number of shares in issue and ranking for dividend during
the year.
(b) The calculation of the loss per share for the year ended
31 December 1998 is based on the loss for the year of £1,850,527
and on 77,717,483 Ordinary Shares, being the number of shares in
issue and ranking for dividend during the year.
4. The preceding financial information does not constitute
statutory accounts as defined in Section 240 of the Companies Act
1985. The financial information for the year to 31 December 1998
is based on the statutory accounts for that year. These
accounts, upon which the auditors issued an unqualifed opinion,
and which did not contain any statement under Section 237(2) or
(3) of the Companies Act 1985, have been delivered to the
Registrar of Companies.