Feb. 19 /PRNewswire/ -- Xenova Group plc (Nasdaq: XNVA; London Stock Exchange: XEN) today announces its results for the year to 31 December 2000.
Announced Today
* Merger with Cantab Pharmaceuticals plc
* XR9576: Phase II Multi-Drug Resistance Programme
-- Third Phase IIa study shows positive interim results
-- Positive responses noted in a number of patients
-- Licensing discussions underway with potential partners
* Completion of Phase II First Generation Dual Topoisomerase Inhibitor
Programme
-- No further development planned for XR5000
* Significant progress with Second Generation Dual Topoisomerase
Inhibitors
-- Phase I/II trials planned for H2 2001
Financial Highlights
* Operating loss from continuing operations unchanged at
9.4m pounds sterling (pounds)
* Total operating expenses decline to 9.5m pounds (1999:13.6m pounds)
Commenting on the results, David Oxlade, Chief Executive Officer of Xenova Group plc said: ``We have made substantial progress in 2000. We are delighted with the positive Phase IIa clinical trial results for our MDR inhibitor XR9576. The first generation dual topoisomerase inhibition programme has provided much useful information which can be applied to speedily advance our second generation compounds, XR11576 and XR5944. These are progressing well and we expect one or other of these compounds to enter clinical trials in 2001.''
Proposed Merger with Cantab Pharmaceuticals plc
Xenova Group plc and Cantab Pharmaceuticals plc today announce that they have agreed terms for a merger of their businesses. The merger will be effected through an all share offer to be made by Nomura International plc on behalf of Xenova Group plc plc for all of the issued (and to be issued) share capital of Cantab Pharmaceuticals plc. The offer is being made outside the United States and is not being made into, and may not be accepted from, the United States. If Xenova Group plc receives acceptances under the offer in respect of, and/or otherwise acquires, 90 per cent. or more of the Cantab Pharmaceuticals plc shares, Xenova Group plc intends to exercise its rights under the Companies Act 1985 to acquire compulsorily the remaining Cantab Pharmaceuticals plc shares.
Chief Executive's Review
Product Development
Both of Xenova's lead drug candidates, the multidrug resistance modulator XR9576 and the novel cytotoxic XR5000, continued to progress through a total of seven Phase II clinical trials during the course of 2000. A number of preclinical programmes were also progressed, and the product pipeline extended with the signing of a research agreement with Brunel University for the development of novel telomerase inhibitors.
XR9576 -- Xenova's P-glycoprotein modulator, which targets the reversal of multi-drug resistance in cancer, progressed through a series of three separate Phase IIa clinical trials during 2000. These trials were designed to assess the extent of pharmacokinetic (PK) interaction, if any, between XR9576 and the marketed cytotoxics paclitaxel, doxorubicin and vinorelbine. The desired outcome of these trials was to show limited or no clinically significant interaction. This outcome would allow the marketed cytotoxic to be administered at or close to its normal therapeutic dose when given in combination with XR9576. Each of the three trials achieved the desired outcome.
Previously Announced Trial Results
The successful conclusion of the paclitaxel trial, which was conducted in relapsed ovarian cancer patients who had previously been treated with a variety of cytotoxic drugs, was announced in March 2000. Although not designed as an efficacy study, complete or partial responses were observed in 6 out of 12 patients.
Further positive data was announced in October 2000 for the second of the Phase IIa trials, in which XR9576 was administered in combination with doxorubicin. Patients participating in this trial suffered from a number of differing relapsed cancers.
Announced Today
Positive interim data has been obtained from the third and final Phase IIa PK interaction study for XR9576, which was given in combination therapy with the cytotoxic drug, vinorelbine (Navelbine). The study has confirmed that, at dose levels of vinorelbine of 15mg and 20mg/m(2), no clinically significant PK interaction was observed and the administration of XR9576 with vinorelbine was well tolerated. Positive responses in several of the patients in the study have been obtained, providing some further anecdotal evidence of efficacy in addition to that obtained in the earlier reported trials.
This open label study, which is being conducted under a US investigational new drug (IND) at the National Cancer Institute, Washington DC, USA, has investigated rising doses of vinorelbine with a single, fixed, once daily administration of 150mg of XR9576 given intravenously. 16 patients have received the combination at dose levels of 15 and 20mg/m(2). The positive PK and toxicity data confirms that XR9576 can be used with the cytotoxic drug vinorelbine administered close to its normal clinical dose, as has been previously reported with prior Phase IIa studies involving XR9576 with paclitaxel and doxorubicin.
A further 12 patients are completing the PK study using a slightly higher dose of vinorelbine of 22.5mg/m(2) and the full results of this Phase IIa vinorelbine study will be presented at the American Society for Clinical Oncology (ASCO) meeting in San Francisco, USA, in May 2001.
Dr Tito Fojo of the National Cancer Institute, and Principal Investigator for the vinorelbine trial, commented:
``The ideal multi-drug resistance modulator should allow cytotoxic drugs to be administered at or as close as possible to their normal dose. XR9576 itself is non-toxic and leaves cytotoxic drug levels largely unaffected. Assays have indicated that a single dose of XR9576 is sufficient to block the action of the P-gp pump for in excess of 24 hours and imaging studies have also indicated that XR9576 can effectively block the P-gp mediated efflux from tumours. Additionally, it is encouraging to see a number of positive responses amongst patients taking part in this study.''
Licensing discussions in relation to XR9576 are currently underway with a number of potential partners, with the objective of taking XR9576 into partner-supported Phase III registration studies during 2001.
XR5000 -- Four Phase II clinical trials were carried out during the course of 2000 for the first generation dual topoisomerase inhibitor known as XR5000. XR5000 is licensed from the Cancer Research Campaign. Along with the second generation compounds XR11576 and XR5944, which are in preclinical devlopment, XR5000 forms part of Xenova's cytotoxic inhibitor programme for the treatment of common solid tumours. Topoisomerases are enzymes which are critically involved in the replication of DNA during the process of cell division and which therefore play a key role in the proliferation of cancer cells. The trials for XR5000 were conducted on an 'open label' basis in conjunction with the European Organisation for the Research and Treatment of Cancer.
Previously Announced Trial Results
The results of the first trial, in which the efficacy of XR5000 was investigated in patients with colorectal cancer, were announced in June 2000. At the study dose no complete or partial responses to treatment were observed and as a result no further recruitment took place in this study.
Announced Today
A further three investigative Phase II studies in ovarian, glioblastoma and non small cell lung cancer patients, which are being carried out with the European Organisation for the Research and Treatment of Cancer (EORTC) are close to completion for XR5000.
Although a number of minor responses have been observed in patients during the course of these studies, the level of these responses has been judged unlikely to provide XR5000 with a commercially attractive profile in the four tumour types studied. Xenova will, therefore, focus its resources going forward on the further development of its second generation dual topoisomerase inhibitor compounds, XR11576 and XR5944. No further development of XR5000 is currently planned.
Pre-Clinical Development
XR11576 -- A novel, orally active second generation dual topoisomerase inhibitor, XR11576 has been undergoing final pharmacological and toxicity testing prior to its planned entry into clinical development. XR11576 has a significantly improved biological profile when compared with XR5000, including oral bioavailability and a marked enhancement of potency. It is structurally dissimilar to XR5000.
XR5944 -- XR5944 is a further novel inhibitor of topoisomerases I and II and has shown exceptionally high potency as a cytotoxic in preclinical studies with a number of cell lines. XR5944 is structurally distinct from both XR5000 and XR11576 and has been shown to be unaffected by atypical multi-drug resistance.
Both XR11576 and XR5944 are the product of Xenova's in-house research and development. Patents have been applied for with respect to both compounds.
It is currently planned that one of these second generation compounds will enter Phase I/II clinical trials during 2001.
PAI-1 Inhibitors (Anti-Thrombotic) -- Research continued throughout 2000 on this programme, which is based on compounds from Xenova's in-house research. These compounds are active in both venous and arterial models of thrombosis and are orally absorbed. Xenova established a partnership with Lilly for this pre-clinical research area in February 1998.
PAI-1 Inhibitors (Anti-Cancer) -- Research is also continuing on this programme in which Xenova is collaborating with the Institute for Cancer Research. PAI-1 is believed to play a role in the spread (metastasis) of cancer. A poster was presented at the VIIIth Congress of the Metastasis Society in September 2000, demonstrating that antibodies to PAI-1 suppress the growth of blood vessels in a solid tumour in vitro.
Multi-Drug Resistance Protein (MRP) -- Research continued during 2000 and it is expected that compounds will enter preclinical development during 2001. Like P-gp, MRP acts as a pump and expels small molecules such as cytotoxics out of cells. Xenova is also exploring the potential application of MRP inhibitors in the prevention of lung inflammation in asthma patients.
Telomerase -- Telomerase is an enzyme known to play a role in cancer progression. In February 2000 Xenova entered into an exclusive collaborative research agreement with Professor Rob Newbold and his team at Brunel University, UK. Professor Newbold and his team are acknowledged as being amongst the world's leading experts in the field of telomerase inhibition.
Management
Peter Gillett joined Xenova's Board as a non-executive Director in February 2000. He chairs Xenova's Audit Committee and was until June 2000 a partner in Ernst & Young, the audit and professional services firm.
Stephen B. Howell, Professor of Medicine at the University of California, San Diego, joined Xenova's Scientific Advisory Board in January 2000.
Financial Summary
Operating Performance
Turnover for the year was 0.1m pounds ($0.1m) (1999: 2.7m pounds ($4.0m)). There was no turnover in the six months to 31 December 2000 (1999: 0.9m pounds ($1.3m)), with the decrease for the year attributable to the transfer in-house to Lilly during 1999 of work in connection with the ongoing Xenova/Lilly strategic cardiovascular research and development programme.
Operating expenses declined to 9.5m pounds ($14.1m) (1999: 13.6m pounds ($20.3m)) and comprised 7.4m pounds ($11.1m) (1999: 11.3m pounds ($16.9m)) of research and development costs and 2.0m pounds ($3.0m) (1999: 2.3m pounds ($3.4m)) of administrative expenses. Research and development costs for continuing operations remained in line with 1999 at 7.4m pounds ($11.1m) (1999: 7.8m pounds ($11.7m)) reflecting further progress through clinical trials by XR9576, XR5000 and the pre-clinical development of the second generation topoisomerase programme in the second half of the year. Continuing administrative costs were 2.0m pounds ($3.0m) (1999: 2.0m pounds ($3.0m)). The operating loss for the year in respect of continuing operations was 9.4m pounds ($14.0m) (1999: 9.4m pounds ($14.0m)) and for the six months to 31 December 2000 was 5.5m pounds ($8.2m) (1999: 5.0m pounds ($7.4m)).
Treasury
In August 2000 Xenova made a placing and open offer of 2,885,108 Units at 345p raising an initial 9.8m pounds ($14.6m). The exercise of warrants linked to this placing and open offer could potentially raise a further 9.8m pounds ($14.6m) net of expenses in 2001. The exercise period for warrants runs from 1 January to 31 October 2001.
Capital expenditure during the year was 0.4m pounds ($0.6m) (1999: 0.1m pounds ($0.2m). There were no proceeds from disposals of tangible fixed assets (1999: 0.2m ($0.3m)) pounds.
Net interest of 0.7m pounds ($1.0m) was earned in the year (1999: 0.5m pounds ($0.7m)). Cash (10.5m pounds ($15.7m)) and liquid resources (1.7m pounds ($2.6m)) at year-end totalled 12.2m pounds ($18.3m) (1999: 10.1m pounds ($15.1m)).
Called up shares at 31 December 2000 were 69,242,577.
The Directors do not recommend the payment of a dividend (1999: nil).
Contacts:
UK: US:
Xenova Group plc Noonan/Russo Communications Inc
Tel: +44-1753-706600 Tel: 212-696-4455
David A Oxlade, Chief Executive Officer Tony Ho Loke
Daniel Abrams, Group Finance Director Amy Martini
Hilary Reid Evans, Corporate Communications |
