Annex M
British Biotech plc
Results for the three months ended 31
October 1994
HIGHLIGHTS
Loss of 6.6 million, well within
budget.
Cash and short-term investments £58.2
million at the end of the quarter.
Encouraging results from Phase I
trial of BB-10010, a new bone marrow protecting drug, and start
of Phase I/Phase II trials in cancer patients announced on 31
October.
Following the end of the quarter,
two drugs, batimastat and lexipafant commenced Phase III clinical
trials.
BB-2516, a potential oral cancer
treatment, started Phase I clinical trials in November.
Clinical plans for 1995 announced.
Commenting, Dr Brian Richards, Chairman said
"Consistent progress has been made in 1994, with both batimastat
and lexipafant moving into Phase III trials and BB-10010 and BB-2516
starting clinical trials. The Board looks forward with confidence
to 1995, during which important results are expected from all
five of British Biotech's clinical programmes".
British Biotech plc
Results for the three
months ended 31 October 1994
CHAIRMAN'S
STATEMENT33
The second quarter maintained British Biotech's
rapid progress in new product development. All three of the company's
new cancer treatments advanced further along their respective
development paths. In particular, the company's breakthrough oral
anti-tumour drug, BB-2516, completed preclinical studies, successfully
following the end of the quarter, and commenced initial human
trials. The injectable drug, batimastat, which is more advanced
in development, remains on track for a European Marketing Approval
Application early in 1996. Thirdly, encouraging early clinical
data was obtained with the new bone marrow protection agent, BB-10010.
Meanwhile, successful Phase II results were announced with the
anti-inflammatory drug, lexipafant, in the treatment of pancreatitis
and this drug is not in Phase III trials.
FINANCIAL
The loss, before and after tax, for the second
quarter of the 1994-95 financial year was £6.6 million (1993-94
: £4.6 million), well within the company's internal budget
for the period. The increase this year is attributable to the
planned rise in operating expenditure related to the progress
across the company's development programmes.
Turnover increased from £693,000 to £858,000.
Turnover mainly represents the continuing EUREKA grant funding,
further income under the biological research agreement with R&D
Systems Europe and income from Glaxo under the collaborative agreement
to develop lexipafant for asthma. Operating expenditure both for
the quarter and the half-year remains within budget. Net interest
increased by £268,000 in the quarter, reflecting the increased
cash balances following the recent Rights Issue.
Cash resources (including cash equivalents and
short-term investments) decreased by £9.6 million in the
period (1993-94 : £6.1 million). The increase over last year
is a result of the increased loss and higher levels of capital
expenditure, principally relating to the construction of new chemical
development facilities in Cowley, Oxford. Cash resources were
£58.2 million at the end of the quarter, slightly ahead of
budget.
RESEARCH AND
DEVELOPMENT
The quarter saw excellent progress for British
Biotech across the company's programmes. Of particular note were
the positive Phase II results for lexipafant in pancreatitis and
encouraging Phase I results for BB-10010, both announced during
the quarter. Clinical progress is described in detail below.
Metalloproteinase inhibitors
Batimastat injectable, the anti-tumour
matrix metalloproteinase inhibitor (MMPI), continued to make good
progress through clinical development in malignant ascites, a
distension of the abdomen with tumour fluid which is a feature
of some late-stage cancers, and pleural effusion, a complication
of lung cancer involving fluid accumulation in the chest cavity.
In October, recruitment was completed in the UK Phase II trial
of batimastat in 40 patients with malignant ascites. The full
results of the trial are expected to be announced at a medical
symposium during 1995, but results to date indicate that safety
and efficacy were similar to those in the Phase I/II study reported
earlier this year. As a result, the company has been able to progress
to a Phase III trial which started after the end of the quarter.
By the end of October, 16 patients with pleural
effusion had been recruited into a Phase I/II study out of a projected
total of 21. Preliminary results look encouraging in that batimastat
has been well tolerated and appeared to prevent reaccumulation
of tumour fluid in the chest in many of the patients assessed
in the study. The company plans to start pivotal trials in 1995.
BB-2516, the company's second generation
MMPI which can be taken by mouth, completed toxicology testing
and other pre-clinical studies successfully and, as a result,
a Phase I clinical trial in healthy volunteers was able to start
after the end of the quarter. The commencement of human clinical
trials with this new drug is a major milestone for British Biotech's
research and development team. The initial volunteer studies are
expected to lead to trials in cancer patients during 1995.
BB-10010
In October, British Biotech announced the initial
results of its Phase I clinical trial with its new bone marrow
protecting drug, BB-10010, and the start of an initial patient
safety trial. The Phase I study was conducted in 36 healthy volunteers
and showed that BB-10010 was well tolerated at all doses. A clinical
trial in patients with various cancers has now begun.
The Phase I study also confirmed findings of
pre-clinical studies conducted earlier this year, which showed
that BB-10010 mobilises white blood cells into the bloodstream.
This finding importantly confirmed the bio-activity of the molecule
in man and is particularly significant in relation to peripheral
bone marrow transplantation (described below).
Potential utility of BB-10010
BB-10010 has two potential clinical uses:
(i) Stem Cell Protection: In this
use, the drug may protect blood stem cells from damage during
cancer chemotherapy. Stem cells are important bone marrow cells
which are the precursors of all blood cells: damage to stem cells
can impair production of white blood cells (which protect against
infection), red blood cells (which carry oxygen) and platelets
(which prevent bleeding). If BB-10010 is confirmed to have stem
cell protection activity in patients, it may reduce the side-effects
of chemotherapy, allowing higher and more effective doses of existing
anti-cancer drugs to be given to patients.
(ii) Stem Cell Mobilisation: In this
use, BB-10010 may mobilise stem cells from their normal location
in bone marrow into the bloodstream. This could allow stem cells
to be harvested from the bloodstream before chemotherapy and then
be replaced after chemotherapy, thus avoiding damage. This process,
known as peripheral blood stem cell transplantation, could replace
much more invasive alternative procedure of bone marrow transplantation.
The initial patient study which has now commenced
is designed to test the safety of BB-10010 in cancer patients.
More extensive studies, designed to test efficacy, are scheduled
to commence over the next three to six months at both UK and US
hospital cancer transplant centres.
Lexipafant
Lexipafant, the company's PAF antagonist, is
being investigated clinically in a number of different diseases.
Pancreatitis
In September, British Biotech announced results
of a Phase II clinical trial of lexipafant in patients with acute
pancreatitis, at a meeting of The European Pancreatic Club in
Bologna, Italy. The Phase II efficacy trial was conducted in 83
patients with pancreatitis, by five participating UK hospitals
co-ordinated by the Royal Liverpool University Hospital. Pancreatitis
is a serious inflammatory disease of the pancreas resulting in
severe abdominal pain which usually requires hospitalisation for
treatment.
Patients treated with lexipafant, when compared
to those receiving placebo, showed a consistent trent towards
a more rapid:
improvement in clinical severity;
and
reduction in systemic and pancreatic
inflammation, as measured by the levels in blood of three different
surrogate markers of inflammation, interleukin-8, interleukin-6
and E-selectin.
Changes in the blood concentrations of inflammatory
markers are known to correlate with disease severity in pancreatitis
and, in particular, interleukin-6 has been shown to be predictive
of clinical outcome. It is therefore noteworthy that, in this
trial, lexipafant reversed the characteristic rise in interleukin-6
in the early stage of the disease. By 24 hours after commencement
of therapy, significant differences between lexipafant and placebo
groups were apparent in blood concentrations of both interleukin-6
and interleukin-8.
As a consequence of these encouraging Phase
II results, lexipafant commenced a Phase III pivotal trial in
pancreatitis after the end of the quarter, intended to confirm
clinical benefit in the treatment of this serious acute disease.
If successful, this Phase III trial in 300 patients may form the
basis of a European Marketing Approval Application.
Sepsis
Lexipafant is also being evaluated in a number
of other acute care conditions, including sepsis and coronary
artery bypass grafting. Preliminary information is now available
from a double-blind, 150-patient Phase II trial of lexipafant
in severe sepsis, which indicates that lexipafant is unlikely
to be of clinical benefit in the treatment of sepsis. Although
the drug was well tolerated and organ function appeared to be
improved partially by treatment, mortality was not significantly
different in treatment and placebo groups. As a consequence of
these results, the company has decided not to pursue further trials
of lexipafant in this indication.
p24-VLP
p24-VLP is being studied in two different formulations,
adjuvanted and unadjuvanted.
Adjuvanted p24-VLP, the AIDS immunotherapeutic,
continued to recruit well in the Phase II studies, with almost
500 patients enrolled into four separate studies. Patient recruitment
is complete in three studies and one study is still recruiting,
a combination study with AZT in Australia. The first results should
be known in the second half of 1995.
Unadjuvanted p24-VLP. The Phase I trial results
were presented at a symposium in the USA after the end of the
quarter. The trial, which was designed to test whether this form
of p24-VLP could induce cytotoxicT lymphocyte (CTL) responses
in humans, showed that p24-VLP without adjuvant can induce a CTL
response, but only at a low level and for a short period. The
company has therefore decided that it will not pursue further
trials with unadjuvanted p24-VLP.
BRITISH BIOTECH
INC
During the quarter, the company announced two
key management appointments in the USA.
Dr Gregory M Hockel PhD joined as Vice President,
Regulatory Affairs. Dr Hockel will oversee British Biotech's regulatory
submissions in the United States including all Investigational
New Drug (INDs) submissions and New Drug Applications (NDAs).
Dr Henrick S Rasmussen MD PhD has joined as
Vice President of Clinical Research and will be responsible for
British Biotech's clinical research programme in the United States.
Dr Rasmussen has had responsibility in other companies for directing
clinical studies in Europe, USA, Japan and Australia/New Zealand,
regularly meeting US investigators and experts as well as the
FDA.
PLANS FOR
1995
1995 promises to be a pivotal year for British
Biotech. All five of the company's leading products will complete
significant clinical trials. While it is difficult to be precise
about timing and results, outline plans are as follows:
Metalloproteinase inhibitors
Batimastatmalignant ascites
The European Phase III study programme currently
comprises two separate multi-centre clinical trials in patients
with malignant ascites. Each trial will enrol 150 patients and
will take approximately one year to complete. The first trial
has now started and is being conducted at approximately 20 hospitals
in the UK. The second trial will commence in early 1995 and will
be conducted at approximately 20 hospitals in Germany, France,
Italy, the Netherlands, Belgium and Switzerland. In addition,
Phase II studies are planned to commence in the first half of
1995 in the USA.
Batimastatpleural effusion
Full results of the current Phase I/II studies
are expected to be released in the second quarter of 1995 at a
major US oncology conference. Pivotal trials in Europe are expected
to start in the first half of 1995. A parallel clinical programme
is being planned in the USA.
BB-2516
If the current Phase I trials show BB-2516 to
be well tolerated and absorbed, Phase II studies should commence
around the middle of 1995. Initially, the company is planning
to test BB-2516 in four different solid tumour types, with parallel
programmes in the UK and the USA.
BB-10010
Following the successful Phase I trial described
above, a further volunteer study will shortly commence in which
the ability of the drug to mobilise bone marrow cells will be
measured. A series of clinical trials in cancer patients is the
next step in developing this compound. Patients will be studied
during receipt of cancer chemotherapy in order to demonstrate
protection of bone marrow cells by BB-10010. One of these studies
is planned for the USA and an IND application has been submitted
to FDA to obtain authorisation for this clinical trial.
Lexipafant
(i) Pancreatitis
Recruitment is due to complete in the Phase III
lexipafant study in patients with severe acute pancreatitis in
the first half of 1996.
(ii) CABG
Results from the Phase II study of lexipafant
in patients undergoing coronary artery bypass graft surgery (CABG)
should be available in late 1995.
(iii) Asthma
The oral version of lexipafant, which is being
evaluated by Glaxo as a treatment for chronic asthma, is scheduled
to enter a large scale Phase II trial in the first half of 1995.
p24-VLP
Results from the clinical trials currently under
way with adjuvanted p24-VLP will be released in the second half
of 1995.
OUTLOOK
1994 has been an active and productive period
for British Biotech. Over 700 subjects were recruited into 26
clinical trials at 65 centres in nine countries. Both batimastat
and lexipafant moved quickly into Phase III trials, while BB-10010
and BB-2516 entered clinical trials for the first time.
1995 will be an even more eventful period for
the company, with all five of the clinical programmes reporting
important data. I look forward with confidence to further progress
being made in 1995.
Brian Richards
Chairman
British Biotech plc
Unaudited consolidated
profit and loss account for the three months ended 31 October
1994
| Quarter ended 31 October 1994 £000
| Quarter ended 31 October 1993 £000
| Half-year ended 31 October 1994
£000
| Half-year ended 31 October 1993
£000
|
Turnover | |
| | |
Continuing operations
(note 1) | 858
| 693 | 1,625 | 1,160
|
Discontinued operation
(note 1) | ¸
| ¸ | ¸ |
1,668 |
|
|
| 858 | 693
| 1,625 | 2,828 |
Operating (loss)/profit |
| | | |
Continuing operations | (7,394)
| (5,107) | (13,764)
| (9,906) |
Discontinued operation | ¸
| ¸ | ¸ |
181 |
| (7,394) | (5,107)
| (13,764) | (9,725)
|
|
|
Loss on disposal of
discontinued operation
| ¸ | ¸ | ¸
| (142) |
Interest receivable | 906
| 638 | 1,784 | 1,338
|
Interest payable | (138)
| (138) | (281) |
(279) |
|
|
Loss before and after tax | (6,626)
| (4,607) | (12,261)
| (8,808) |
Loss per share (note 2) | (13.7p)
| (11.9p) | (25.6p)
| (22.8p) |
| |
| | |
British Biotech plc
Unaudited consolidated profit and
loss account for the three months ended 31 October 1994
| Quarter ended 31 October 1994
£000
| Quarter ended 31 October 1993
£000
| Half-year ended 31 October 1994
£000
| Half-year ended 31 October 1993
£000
|
Net cash outflow from
operations | (7,530)
| (5,828) | (13,348)
| (10,492) |
Return on investments |
| | | |
Net interest | 142 |
319 | 528 | 489
|
Investing activities |
| | | |
Purchase of fixed assets | (2,231)
| (578) | (3,406) |
(1,769) |
Disposal of discontinued
operation |
- | ¸ | ¸
| 879 |
Net sale of short-term
investments |
4,500 | ¸ | 6,500
| ¸ |
|
|
Cash outflow before
financing | (5,119)
| (6,087) | (9,726)
| (10,893) |
Financing | |
| | |
Issue of share capital | 59
| 1 | 45,934 | 1
|
Repayment of loan | (67)
| ¸ | (135) |
¸ |
|
|
Cash (outflow)/inflow
from financing |
(8) | 1 | 45,799
| 1 |
(Decrease)/increase in cash
and cash equivalents
| (5,127) | (6,086)
| (36,073) | (10,892)
|
Cash and cash equivalents |
| | | |
At start of period | 63,280
| 45,397 | 22,080 |
50,203 |
Increase/(decrease) in
period | (5,127)
| (6,086) | (36,073)
| (10,892) |
|
|
At end of period | (58,153)
| (39,311) | (58,153)
| (39,311) |
British Biotech plc
Unaudited Consolidated Balance Sheet
at 31 October 1994
| 31 October 1994 | 30 April 1994
|
| £000 | £000
|
Tangible fixed assets | 21,065
| 18,671 |
Current assets | |
|
Stocks | 73 |
63 |
Debtors | 3,767
| 1,555 |
Short-term investments |
| 6,500 |
Cash and cash equivalents | 58,153
| 22,080 |
| 61,993 | 30,198
|
Creditors due within one year | (6,087)
| (5,442) |
Net current assets | 55,906
| 24,756 |
Total assets less current liabilities
| 76,971 | 43,427 |
Creditors due after more than one year
| (3,897) | (4,028)
|
Net assets | 73,074
| 39,399 |
Capital and reserves |
| |
Share capital | 2,415
| 1,811 |
Share premium | 141,239
| 95,907 |
Profit and loss account | (70,580)
| (58,319) |
Shareholders' funds | 73,074
| 39,399 |
| |
|
NOTES:
1. The discontinued operation in the half-year ended
31 October 1993 related to the reagents and diagnostics business
British Bio-technology Products Limited, which was sold to Techne
Corporation on 30 July 1993.
2. Losses per share
(a) Quarter ended 31 October 1994
Losses per share are based on the loss attributable to shareholders
before and after taxation of £6.6 million (1993: loss of
£4.6 million) and on 48.3 million (1993: 38.6 million) shares,
being the weighted average number of shares in issue for the quarter.
(b) Half-year ended 31 October 1994
Losses per share are based on the loss attributable to shareholders
before and after taxation of £12.3 million (1993: loss of
£8.8 million) and on 47.8 million (1993: 38.6 million) shares,
being the weighted average number of shares in issue for the half-year.
In calculating the weighted average number of shares, the
number of shares in issue prior to the Rights Issue have been
adjusted to reflect the bonus element of the Rights Issue.
3. The financial information on the group set out above
does not constitute statutory accounts within the meaning of Section
240 of the Companies Act 1985. The financial information for the
year ended 30 April 1994 is an extract from the group's statutory
accounts which have been delivered to the Registrar of Companies;
the report of the auditors on these accounts was unqualified and
did not contain a statement under Section 237(2) or (3) of the
Act.
|