LONDON, Dec. 10 /PRNewswire/ -- Celltech today reports important progress
with its two leading product candidates, CMA676 and CDP 571, both of which are
in late phase clinical studies. This is coupled with a strong financial
performance, underpinned by substantial growth in licensing income arising
from Celltech's antibody technology.
-- CMA 676 -- Acute Myeloid Leukaemia: Further promising results have
been obtained with this novel drug, with a total of over 90 first
relapse patients having now been treated in a US pivotal and supporting
studies undertaken by American Home Products.
The new positive results obtained to date, details of which will be
published in due course, are closely comparable to previous findings in
an initial group of 23 patients, in which 43% had complete or major
responses, with complete elimination of leukaemic cells.
It is expected that US marketing authorisation for CMA676 will be
sought in mid-1999.
Since the year end, revised commercial arrangements have been agreed
with AHP which provide Celltech with a significantly improved worldwide
royalty rate, in exchange for Celltech's share of European marketing
rights.
-- CDP 571 -- Crohn's Disease: Rapid progress has been achieved with
this humanised anti-TNF(a) antibody which was granted Fast Track
designation by the US FDA. Patient recruitment has been completed in a
potentially pivotal Phase IIb study in Crohn's Disease, and is close to
completion in a second study. Filing of a US Biologics Licence
Application is currently expected in 2000.
-- There have been substantial advances with other clinical and
preclinical programmes including the following:
i) The antibody-cytotoxic drug conjugate CMB 401, under development
with American Home Products, has entered a Phase II trial in
ovarian cancer in seven US and two UK centres, following
encouraging findings in an initial study in advanced ovarian cancer
patients.
ii) The novel anti-cytokine product, CDP 870, has entered an initial
Phase II study in rheumatoid arthritis in four UK centres.
-- Reflecting its financial strategy the Company ended the year with a
cash position of 40.2 million British pounds sterling (1997:
36.3 million pounds) and a loss reduced to 3.1 million pounds (1997
loss: 12.1 million pounds), notwithstanding an R&D investment of
21.5 million pounds (1997: 18.2 million pounds). These results were
partly due to a large increase in turnover to 11.7 million pounds
(1997: 4.3 million pounds) comprising licensing income arising from
recently marketed third party products which utilise Celltech's
antibody technology. Further, an exceptional profit of 5.4 million
pounds arose from the sale of Celltech's remaining 25% interest in
Lonza Biologics for 10.5 million pounds in December 1997.
Dr. P. Fellner, Chief Executive, said "This has been a year of important
progress for Celltech. There have been major advances with the leading
products in our clinical pipeline, the benefits of which will begin to accrue
within the next 1-2 years. In addition, Celltech's antibody technology is
providing rapidly growing licensing income, which is further reinforcing the
Company's strong financial position."
CELLTECH PLC
Preliminary Announcement
Further details of Celltech's progress during the year are summarised
below:
Clinical Programmes
CMA676 -- Acute Myeloid Leukaemia
American Home Products is continuing a US pivotal study on CMA676, a novel
treatment for acute myeloid leukaemia (AML). Earlier this year, we reported
encouraging results from an interim analysis of the initial group of
23 patients in this pivotal study, with 10 (43%) of the patients having a
complete or major response to treatment, characterised by complete elimination
of clinically evident leukaemic cells. Of these, 3 (13%) had complete
remission (complete disease clearance and restoration of normal blood counts).
These results were presented in more detail on 7th December 1998 at the
American Society of Haematology Meeting in Miami.
A total of more than 90 patients have now been treated with CMA676
worldwide in the pivotal and supporting Phase II studies. The positive
results which have been obtained to date from the larger patient database are
closely comparable to the earlier findings, and we continue to be encouraged
by the preliminary clinical profile. It is intended to publish these results
in detail in due course.
The preliminary safety profile of CMA676 also continues to be promising,
enabling patients to be treated in an outpatient setting. The most common
side-effects are transient fever, chills and rigors. In addition, neutropenia
and thrombocytopenia (low platelet counts) are seen, generally lasting
2-5 weeks after CMA676 administration.
Supporting Phase II studies are continuing in first relapse adult AML
patients in Europe, and in elderly patients in Europe and the US. A further
study in paediatric AML patients will begin in the near future. The pivotal
and Phase II studies are intended to support US and worldwide marketing
authorisation applications, which are expected to be submitted in mid-1999.
CDP 571 -- Crohn's Disease
Celltech is undertaking two Phase IIb clinical studies in the serious
inflammatory bowel disorder, Crohn's disease, with the engineered human
antibody CDP 571 which binds to TNFa. These studies are being carried out in
leading centres in the US, Canada and the UK, following appropriate regulatory
approvals. The FDA has granted Fast Track designation for CDP 571, and
therefore, if these studies are successful, it is expected that a US Biologics
Licence Application will be filed in 2000.
The trials, which will involve approximately 230 patients, comprise:
(i) A six-month dose-ranging study in patients with active Crohn's
disease, to evaluate efficacy and duration of action.
(ii) A four-month study to determine the ability of CDP 571 to reduce
steroid dependency in patients maintained in remission by steroids.
Both studies are placebo-controlled and double-blinded. The
placebo-controlled phase will be followed by further treatment administered
during a six month open phase, in order to provide safety data on the product
during a treatment period of up to 12 months. Recruitment has already been
completed in the main study in active Crohn's disease, and is close to
completion in the steroid withdrawal study. It is expected that the
placebo-controlled phases of these studies will be concluded by mid-1999, with
results available in Q3 1999.
Discussions of partnership opportunities for the late phase development
and marketing of this product are currently ongoing with a number of major
pharmaceutical companies.
CMB401 -- Ovarian Cancer
CMB401, an anti-PEM antibody-calicheamicin conjugate, has now entered a
Phase II clinical study in ovarian cancer, conducted by American Home
Products. This is being undertaken with patients who have previously
responded to treatment with platinum-based chemotherapy and have subsequently
relapsed. This study which is being carried out in 7 US and 2 UK centres,
will enroll up to 64 patients. The patients are being treated with up to
7 doses of CMB401 at 16mg/m(2), administered at monthly intervals. The
interim review of the findings in an initial group of patients will be
undertaken in 1999. If the findings are encouraging, AHP may expand the study
to patients who have proved refractory to platinum-based chemotherapy.
This Phase II study follows on from encouraging initial results in an
ascending dose safety and efficacy study in 34 patients with advanced ovarian
cancer, reported at the American Society of Clinical Oncology Meeting in May
1998. In the 21 patients treated at the highest doses, three showed evidence
of substantial reduction of tumour bulk assessed by CT scanning. Other
patients showed reductions in levels of a tumour-associated antigen in the
blood.
In parallel Celltech is carrying out a pilot ascending dose safety and
efficacy study of CMB401 in non-small cell lung cancer patients in two UK
centres, to assess whether this product will have therapeutic potential in
this indication. This study is expected to be completed in 1999.
SCH55700 -- Asthma
Schering-Plough are undertaking an ascending dose clinical study with this
humanised anti-interleukin-5 antibody in asthma patients. The study aims to
provide safety information and, if the results are satisfactory, it is
expected that full Phase II efficacy studies will be carried out.
Pharmacokinetic data from the ascending dose study has shown that the
antibody displays a plasma half-life in patients of about 25 days, and
relatively high blood levels are detectable after three months. In
preclinical models, the antibody also displayed a prolonged half-life, and a
single dose of the antibody inhibited responses to antigen challenge
three months after administration.
CDP 870 -- Rheumatoid Arthritis
CDP 870 is a novel anti-cytokine antibody fragment which is produced by
Celltech's new proprietary low-cost manufacturing technology in E.coli. This
results in a reduction of manufacturing cost of up to ten-fold compared to
current antibody production methods. The antibody fragment is subsequently
chemically modified. A Phase I clinical study with CDP 870 in volunteers was
successfully completed earlier this year. It was found that this modified
antibody fragment exhibited a plasma half-life of 11 days in this study group,
a value similar to that which full-length unmodified humanised antibodies
achieve.
Following approval of a UK CTX, CDP 870 has entered a Phase II ascending
dose clinical study in rheumatoid arthritis patients in four leading UK
rheumatology centres. Approximately 40 patients will be enrolled in this
placebo-controlled trial, whereby patients will receive a single dose of CDP
870 and will be assessed over an 8 week period. The study protocol provides
for patients to receive a further dose of the product in a subsequent open
phase of the study. It is expected that the study will be completed in the
second half of 1999.
CDP 850 -- Psoriasis
A small placebo-controlled Phase I/II study has been carried out with CDP
850, a humanised anti-E selectin antibody, in patients with moderate to severe
psoriasis. Reductions in psoriasis scores were seen in some patients, but the
extent of clinical benefit indicated that CDP 850 was unlikely to represent a
significant commercial opportunity. This conclusion was reinforced by the
potential requirement to re-engineer the antibody for manufacture in E.coli in
order to reduce its production costs. The antibody will not therefore be
further developed in this clinical indication.
Separately, this antibody is being evaluated as a potential targeting
vehicle in a preclinical oncology programme.
Preclinical Programmes
CDP 860 -- Coronary Restenosis
CDP 860 is a chemically modified antibody fragment which binds to
platelet-derived growth factor (PDGF)(b) receptor. It is also manufactured
with Celltech's low cost bacterial production technology. This product
candidate, which arose from a collaboration with the ZymoGenetics affiliate of
Novo Nordisk, is currently undergoing preclinical safety studies, and is
expected to enter Phase I clinical studies in 1999. If the Phase I findings
are satisfactory, it will enter a Phase II proof-of-concept trial in
angioplasty patients.
CDP 855 -- Transplantation
CDP 855 is a novel human antibody which binds specifically to a region of
the Class II MHC complex and blocks antigen presentation. It has potent
immunosuppressive activity in a number of model systems. On the basis of
current efficacy data, its therapeutic activity is being studied in
transplantation models, both as a single agent and in combination with
existing treatments for prevention of graft rejection. This is being
undertaken in collaboration with a major pharmaceutical company.
Discovery Programmes
The major element of Celltech's investment in research and development is
in its drug discovery programmes and associated technology. These programmes
use both engineered human antibodies and new chemical entities to address
novel therapeutic targets. Progress in the largest discovery programmes,
which are being undertaken either internally or with collaborators, is
summarised below:
Phosphodiesterase IV Inhibitors -- Asthma
This programme, which is being undertaken in collaboration with Merck,
aims to identify potent and selective PDE IV inhibitors for the treatment of
mild to moderate asthma. Most work in this programme is being carried out by
Merck. Further progress has been made during 1998 and a number of compounds
are currently being evaluated as potential candidates for entry into
development. Merck made further time-based payments of 1.3 million pounds to
Celltech during the year.
Integrin Antagonists -- Asthma and Inflammatory Bowel Disorders
This programme, which is the largest discovery programme currently
undertaken within Celltech, has achieved major advances during 1998. The
programme aims to identify novel disease-modifying treatments for asthma which
will reduce airway inflammation by a new mechanism and which will be orally
active. A number of series of non-peptidic compounds have been identified
which block the binding of the integrin molecule VLA4 (very late antigen 4).
These compounds, which are potent and highly selective, have been found to
display oral activity in several tertiary asthma models. During the year
substantial progress has been made in optimising the pharmacokinetic profiles
of the lead antagonists. In parallel, a further programme is being pursued,
which aims to develop new approaches to treating inflammatory bowel disorders
with antagonists which bind to another related integrin molecule.
Aggrecanase Inhibitors -- Osteoarthritis
The programme which aims to develop a novel approach to the treatment of
osteoarthritis, is being carried out in collaboration with Zeneca, and most of
the current studies are being pursued within their research laboratories. A
range of potent inhibitors of aggrecanase have been identified and
optimisation and evaluation of these leads is continuing.
Financial Results
Turnover, comprising licence fees and royalty income, increased
significantly to 11.7 million pounds for the year (1997: 4.3 million pounds).
Included in this figure were two up-front licence fees paid by Centocor in
respect of Remicade(TM) (formerly known as Avakine(TM)), an anti-TNF antibody
targeted at Crohn's disease and rheumatoid arthritis, which has recently been
launched in the US. Royalty income arising from licences granted to
Celltech's Boss patents, was received on increasing sales of ReoPro(TM)
(currently selling at $350 million per annum) and Rituxan(TM), an antibody for
non-Hodgkins lymphoma launched in December 1997. Royalty income is expected
to advance strongly in 1998/99 with a total of seven antibody products,
subject to Boss licences, now having been launched in the US or Europe.
In August 1998 the US Patent Office made an important and emphatic
decision in favour of Celltech in a patent interference between Celltech's
Boss patent and Genentech's Cabilly patent. It upheld Celltech's patent, on
the basis of the priority date of the invention. This decision concluded the
interference process which had continued for eight years. This outcome has
subsequently been appealed by Genentech. Celltech is confident that the US
Patent Office decision will be upheld and will vigorously defend its position
during the further legal process, which it has been advised is likely to be
prolonged.
Investment in R&D increased 18% to 21.5 million pounds (1997:
18.2 million pounds), primarily as a result of increased external development
costs, comprising clinical trials and manufacturing for CDP 571 and CDP 870.
Corporate and general overheads of 2.9 million pounds increased 5% over 1997
(2.7 million pounds).
Other income, principally comprising the time-based payments of
1.3 million pounds from Merck in respect of the PDE IV programme, was lower
than 1997 (2.2 million pounds). This reflected a small reduction in the
contractual terms for time-based payments after the first three years of the
Merck programme. In total Celltech has received over 13 million pounds from
Merck since the inception of the programme.
The sale on 31st December 1997 of the remaining 24.9% interest held by
Celltech in Lonza Biologics, Celltech's former manufacturing business,
provided cash proceeds of 10.5 million pounds and generated a profit of
5.4 million pounds during the year. In total Celltech has received
42.1 million pounds and realised a profit of 17.5 million pounds on the
disposal of the Biologics business.
As a result of the foregoing, the loss for the year was 3.1 million
pounds. Excluding the exceptional profit on the sale of the interest in
Biologics, the underlying 1998 loss was reduced to 8.5 million pounds (1997
loss: 12.1 million pounds). The cash position at 30th September 1998 remained
strong at 40.2 million pounds (1997: 36.3 million pounds). The Board
continues to expect that Celltech's cash resources will be adequate to support
its normal operational requirements without further equity finance until the
Company enters sustained profitability. This is anticipated to occur in the
year ending September 2000 assuming that product registration proceeds to
plan.
Consolidated Profit and Loss Account
for the year ended 30 September 1998
1998 1997
millions of pounds
Turnover 11.7 4.3
Investment in research and development (21.5) (18.2)
Corporate and general administrative expenses (2.9) (2.7)
Other operating income - research and
development milestones 1.5 2.2
Operating loss (11.2) (14.4)
Profit on sale of Biologics 5.4 --
Net interest receivable 2.7 2.4
Loss on ordinary activities before taxation (3.1) (12.0)
Taxation -- (0.1)
Loss on ordinary activities after taxation (3.1) (12.1)
Accrual for unpaid preference share dividend
transferred to other reserves 0.2 0.2
Transfer from Profit and loss account reserve (3.3) (12.3)
Net transfer (from)/to reserves (3.1) (12.1)
Loss per share: Basic and Diluted (4.4p) (16.2p)
The financial statements shown above are in an abridged form and do not
constitute the Company's Annual Report and Accounts for the years ended
30 September 1998 or 1997, but are extracted from those accounts. The
Annual Report and Accounts for 1997 have been delivered to the Registrar
of Companies, and those for 1998 will be sent to shareholders in January
1999. The auditors have reported on those accounts; their reports were
unqualified and did not contain statements under section 237(2) or (3) of
the Companies Act 1985.
The Directors do not recommend the payment of any dividend.
Consolidated Balance Sheet
at 30 September 1998
1998 1997
millions of pounds
Fixed assets
Tangible assets 7.1 6.5
Investments -- 0.2
7.1 6.7
Current assets
Stock 0.9 --
Debtors 0.8 0.8
Investments (Note 1) -- 6.4
Cash and Liquid resources 40.2 36.3
41.9 43.5
Creditors: amounts falling due within one year (7.1) (5.9)
Net current assets 34.8 37.6
Total assets less current liabilities 41.9 44.3
Creditors: amounts falling due after
more than one year
Obligations under finance leases (0.2) (0.3)
Net assets 41.7 44.0
Capital and reserves
Called up share capital 41.8 41.6
Share premium account 60.9 60.3
Other reserves 10.3 10.1
Profit and loss account (71.3) (68.0)
Shareholders' funds 41.7 44.0
Note 1 On 31 October 1997 Celltech exercised its Put option with
Alusuisse-Lonza for the transfer of its remaining 24.9% holding
in the share capital of Lonza Biologics. Payment for this
transfer of 10.5m pounds was received on 31 December 1997. The
book value of the investment was 6.4m pounds, which, along with
the release of provisions related to the sale, gave rise to a
profit of 5.3m pounds. In addition an earn out payment was
received in February from Alusuisse-Lonza of 0.1M pounds in
respect of the 15 months ended 31 December 1997.
Consolidated cash flow statement
for the year ended 30 September 1998
1998 1997
millions of pounds
Net cash outflow from operating activities
(Note 2) (8.4) (12.7)
Returns on investments and servicing of finance -
Net interest 2.7 2.4
Tax paid (0.1) --
Capital expenditure and financial investment (1.5) (1.1)
Acquisitions and disposals -
Net receipt from sale of 24.9%
of Celltech Biologics plc 10.5 --
Earn out payment from Alusuisse-Lonza 0.1 --
Cash generated/(utilised)
by business activities 3.3 (11.4)
Financing 0.6 1.3
Total increase/(decrease) in cash
and liquid resources 3.9 (10.1)
Note 2 Reconciliation of operating loss to net cash outflow from
operating activities
1998 1997
millions of pounds
Operating loss (11.2) (14.4)
Depreciation 1.0 0.9
(Increase)/decrease in stocks (0.9) 1.0
Increase/(decrease) in creditors 2.7 (0.2)
Net cash inflow/(outflow)
from operating activities (8.4) (12.7)
SOURCE Celltech plc
 back to top
Company News On-Call:
http://www.prnewswire.com/comp/136465.html or fax,
800-758-5804, ext. 136465
CONTACT:
Peter Fellner, Chief Executive,
44-1753-777101, or Peter Allen, Finance Director, 44-1753-777100,
both of Celltech plc; or Jon Coles of Brunswick, 44-171-404-5959,
for Celltech plc
|
