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Hier eine kleine Zusammenfassung einiger Fakten. Sie suchen immer noch nach einem Partner für die dritte Phase von XR9576 ind wenn Sie den finden, poste ich wieder bei 3 Euro. XENOVA Xenova was founded in 1987 with the objective of developing proprietary drug discovery technologies based on naturally occurring plants and organisms. Following a 1998 strategic review, the company`s natural products based drug discovery service business, Xenova Discovery, was sold to TerraGen Diversity Inc. of Canada in March 1999. The business of its US based subsidiary, MetaXen, was sold to Exelixis Inc. in July 1999. Xenova`s efforts are now concentrated on proprietary drug development, primarily in the area of cancer therapeutics. Chief Executive David Oxlade joined Xenova in June 1997 and was appointed Group Chief Executive in March 1998. Originally trained as a biochemist, he has over 25 years experience in the global healthcare industry. He was previously President of the Syva Division of Behring Diagnostics Inc. Michael Moore is the Chief Scientific Officer. He joined XEN in 1988 from the Paterson Institute for Cancer Research in Manchester, England, where he held a Cancer Research Campaign Special Appointment. He is also an honorary professor in the Department of Biology and Biochemistry at Brunel University, Uxbridge. The Research and Development Director is John Waterfall, joining Xenova in May 1999, from Hoffmann-La Roche Inc. He has spent 27 years in various pharmaceutical research and development roles with major companies in both Europe and the USA. Xeneva`s Scientific Advisory Board (SAB) was substantially restructured in May 1999 to reflect the company`s strategic focus on oncology-related drug discovery and development. It is chaired by Professor Stan Kaye, who is also head of the Cancer Research Campaign Department of Medical Oncology at the University of Glasgow. Professor Paul Workman is a Director of the Cancer Research Campaign Centre for Cancer Therapeutics Institute of Cancer Research, London. He is also Chairman of the Cancer Therapeutics Section of the Institute of Cancer Research and Harrap Professor of Pharmacology and Therapeutics at the University of London. Stephen Howell, Professor of Medicine at the University of California, San Diego, was appointed to Xenova`s Scientific Advisory Board (SAB) in January 2000. He is acknowledged as a leading world expert in the field of cancer therapeutics and is a recipient of the Milken Family Medical Foundation Award for Outstanding Work in the Field of Cancer Research. Xenova`s strategy is to develop commercially attractive new drugs, primarily in the area of cancer therapeutics. The company currently has two drug candidates, XR9576 and XR5000, undergoing Phase II clinical trials, and a number of drug leads undergoing optimisation or evaluation. In addition to XR9576 and XR5000, Xenova is also currently undertaking cancer research projects targeting MRP-related multi-drug resistance, next generation topoisomerase inhibitors, telomerase (with Brunel University) and plasminogen activator inhibitor-1 (PAI-1). The company has a drug development agreement with Eli Lilly, based on small molecule inhibitors of PAI-1, to develop novel antithrombotic drugs for chronic use. Commercial History Research is continuing in the drug development programme, in which Xenova established a partnership with Eli Lilly in February 1998. The partnership is based on compounds from Xenova`s XR334 series which are capable of oral absorption and are active in both venous and arterial models of thrombosis. Under the partnership Xenova will receive up to $35 mln over five years in license fees, research funding and milestone payments over the drug development cycle, subject to the achievement of certain objectives. Approximately $10 mln in total was received from Eli Lilly in the period from February 1998 to 31 December 1999. Xenova made considerable progress in the first six months of 2000 in development of its product pipeline. The company continues to be clearly focused on the discovery and development of valuable new drugs and has two oncology-related products, the P-glycoprotein modulator XR9576 and the cytotoxic agent XR5000, nearing the end of Phase II clinical trials. Interim results from the trials for XR9576 are particularly encouraging and, although the results of the colorectal trial for XR5000 proved disappointing, results from the three further XR5000 trials (for ovarian and non-small cell lung cancers and glioblastoma), which are expected during the fourth quarter 2000,will help determine the future development strategy for this compound. It is the Group`s intention to seek commercial partners for its products, generally no later than the start of Phase III clinical trials. Two new second-generation cytotoxics, both discovered through Xenova`s in-house research and development capability, are nearing the end of preclinical development. The first of these, XR11576, is expected to enter clinical studies in 2001.Xenova`s collaborative research agreement for the discovery and development of apoptosis inducing telomerase inhibitors, with Brunel University (one of the UK`s leading universities in this field) has further strengthened the Group`s preclinical pipeline. Product Pipeline * XR9576¹ - targeted at the most common form of multi-drug resistance (MDR) MDR is the result of over-production in the cancer cell membrane of P-gp, a protein which pumps the anti-cancer drug out of the cell. This may affect between 30% and 80% of all cancer patients affected by MDR, depending on the cancer type. * XR5000² - being developed as a drug to treat solid tumours XR5000 is currently in Phase II clinical trials. The drug has demonstrated significant activity in preclinical animal models against several types of cancer, including multi-drug resistant cancers. Final data from the three ongoing Phase II trials are expected to be available by the end of calendar year 2000. * XR11576³ - aimed at a similar target to XR5000, i.e. solid tumours XR11576 retains the benefits XR5000 potentially provides, but has a superior profile, due to its greater potency and oral bioavailability. The drug is currently undergoing pharmacological and toxicity testing prior to its possible nomination for entry in to clinical trials. * XR5944 - again, aimed at a similar target to XR5000, i.e. solid tumours XR5944, although structurally different to both XR5000 and XR11576, has shown exceptionally high potency as a cytotoxic agent in preclinical studies with a number of tumour cell lines. Cancer Research The primary focus of Xenova`s drug research and development programmes is cancer (oncology). Cancer is a therapeutic area in which there is a considerable need for new and better treatments. In the US, Western Europe and Japan, an estimated 3 mln people each year are diagnosed with cancer. Cancer is characterised by abnormal cell growth resulting in the development of a mass of cells commonly known as a tumour. Cancer can arise in almost any tissue or organ within the human body. Drugs obtained from nature have played and continue to play a central role in cancer chemotherapy. Natural chemicals and many other current methods of cancer chemotherapy treat the disease by killing cancer cells directly. However, the use of such drugs may be limited by their adverse side effects and the existence of resistance mechanisms in tumour cells. Research into the process of tumour growth, multi-drug resistance and the spread of cancer to other organs (known as metastasis) has now identified critical disease mechanisms as specific targets for new approaches to cancer therapy. Xenova focuses on targets in these areas, with the aim of producing drug candidates with the potential for improved efficacy and reduced side effects relative to currently available therapies. The company is currently conducting cancer drug discovery research targeting topoisomerases I and II, multi-drug resistance, PAI (plasminogen activator inhibitor-1) and telomerase. Xenova is currently undertaking Phase II clinical trials for its two most advanced drugs, XR9576 and XR5000. Pre-clinical development of Xenova`s pipeline of compounds continued throughout the first half of 2000. All preclinical compounds currently in development have been derived from Xenova`s own R&D capability. With regard to XR5944, it is structurally distinct from both XR5000 and XR11576 and has been shown to be unaffected by atypical MDR. A UK priority patent application relating to the XR5942 second generation of drug leads has been filed by Xenova. XR5944 forms part of this family of drug leads. Patents granted pursuant to these applications, if any, would expire in 2017. PAI-1 Inhibitors (Anti-Thrombotic) PAI-1 Inhibitors (Anti-Cancer) research continued throughout the first half of 2000 in this programme, in which Xenova is collaborating with the Institute for Cancer Research. PAI-1 is believed to play a role in the spread of cancer (metastasis). In a number of types of tumours susceptible to metastasis, a strong correlation has been observed between elevated PAI-1 levels, disease progression and reduced patient survival time. Xenova presented `proof of concept` studies in this area in 1999. Lilly has been granted an option to acquire exclusive rights to develop and commercialise PAI-1 inhibitors in this field. If exercised, Xenova could receive up to $16.5 mln in aggregate together with additional royalties on commercialised products. Xenova is conducting a research programme for Multi-Drug Resistant Protein (MRP) during 2000. Should this be successful, it is expected that the project will enter preclinical development during 2001. MRP acts as a pump, which, like P-gp, expels small molecules (such as cytotoxins) out of cells and thus can help protect tumour cells from certain chemotherapeutic agents. XEN is also exploring the potential application of MRP inhibitors in the prevention of lung inflammation in asthma patients. The company is currently evaluating drug leads from its MRP cancer programme in the search for new classes of anti-asthmatic drug candidates. Telomerase is an enzyme known to play a role in cancer progression. In February, Xenova signed an exclusive collaborative research agreement, lasting at least two years, for the discovery and development of novel classes of apoptosis inducing telomerase inhibitors with Brunel University (one of the United Kingdom`s leading universities in this field). TerraGen Investment On August 5 TerraGen Discovery Inc. entered into an acquisition agreement with, among others, Cubist Pharmaceuticals. Cubist will, indirectly, acquire the outstanding shares of TerraGen in exchange for shares of Cubist common stock, or shares of a subsidiary of Cubist which are exchangeable for shares of Cubist common stock and will assume the convertible note held by Xenova, which will be converted into a debenture convertible into shares of Cubist common stock. It is anticipated that under, or in connection with, this transaction, Xenova will receive 91,048 shares of Cubist common stock in exchange for its holding of 1m Class B preferred shares and following conversion of the £1.5m convertible note in TerraGen which can occur in April2001. These investments were each carried in Xenova`s balance sheet at 30 June 1999 at £1.5m, and current prices would suggest a value now of approximately £2.9 mln. The Financials In July, Xenova raised an initial £9.8 mln, before expenses, by issuing 2,885,108 units, each unit comprising 5 new ordinary shares and 4 warrants, at 345p per unit, via a Placing and Open Offer, underwritten by Nomura, in order to complete the ongoing Phase II clinical trials for its lead products XR9576 and XR5000 and, together with a partner, conduct Phase III trials, if appropriate. In addition, Xenova will raise a further approximately £9.8 million, before expenses, assuming full exercise of the warrants at 85p per warrant, up to the end October 2001. As a result of the Placing and Open Offer, the issued ordinary share capital has increased from 54,817,037 ordinary 10p shares to 69,242,577. Again, as was the case with Oxford BioMedica, because of the very nature of biotechs, the cash burn rates and losses, either as a headline number or in my favoured operational comparison, Gross Cash Flow, are fairly much mitigated. The point is that one is trying to invest in the future, and the current financial data are, in a sense, somewhat meaningless. But with an excellent management in place, and with the continued growth in cancer victims, I believe one needs to focus on the potential of a breakthrough in the drug pipeline. Consensus forecasts are for a loss per share of 14p in the year to 31 December 2000, followed by a loss of 9.6p in 2001. Last month, Xenova reported third quarter figures that showed the Q3 operating loss was £2.5 million, including R&D costs of £2.1 million, which reflected the increased costs of Phase II clinical trials for its leading XR9576 and XR5000 drugs. Nil revenues occurred in the quarter, with total revenue for the nine months to September 30 of £100,000 primarily derived from the sale of a software license. The product pipeline "generally made good progress in the first nine months of this year." A brief look at the 1999 numbers, then. 1998 figures are in brackets. All data are expressed in £000s, except per share data. Current share price 107p Shares outstanding 69.2 mln Market capitalisation £74.1 mln 1999 (£000s) 1998 (£000s)Turnover 2,693 ( 4,865)Operating Losses -10,926 (-14,636)R&D costs 11,294 ( 16,482)EBITDA -10,075 (-13,567)EBIT -10,655 (-14,636)Gross Cash Flow -10,075 (-13,567)Return on Equity -87.04%Return on Assets -86.13%Net Asset Value per share (NAV) 16.78pPrice/Book 6.38Operating Cash Flow/Operating Profit 104.2%Average collection period 105.4 daysCurrent ratio 4.68Quick (acid test) ratio 4.46 Major Shareholders:Prudential plc 10.32%Bank of New York 9.96%Hermes Investment Management Limited 5.40%Framlington Group PLC 5.03%INVESCO 3.34%Nomura Capital Management 3.96%Hyson Ltd 3.65%BriTel Fund 3.36%Scottish Mutual 3.28% The market cap of Xenova gives some confidence in two ways. First, it`s a small fish, financially, in the world of biotechnology. Yet, its technology is first class. Its diverse approach, plus its extensive partnership agreements, should enable it to further explore some of the most needed areas of cancer research. Second, I still believe there is scope for consolidation in this sector. Combining and sharing intellectual property, with either another biotech, or a major pharma, will undoubtedly lead to cost savings, and a better platform from which to negotiate licensing and milestone deals. Bullet Notes: 1. XR9576 is a P-glycoprotein pump (P-gp) inhibitor, designed to address the problems of multi-drug resistance in cancer. It is estimated that, depending on the type of cancer, between 30% and 80% of cancer patients develop resistance to anti-cancer drugs. The most common form of this resistance is the over-production of a membrane protein, known as P-gp, which pumps anti-cancer drugs out of cells. XR9576 (P-glycoprotein modulator) was recently used in a successfully completed Phase II apharmacokinetic study in relapsed ovarian patients. It is expected that XR9576 will be ready to enter Phase III clinical trials in late 2000. The company does not, however, intend to progress XR9576into Phase III trials until a licensing partner has been secured to provide financial support for the conduct of these trials. A further two Phase IIa clinical trials, in which XR9576 is being studied in combination therapy with doxorubicin and vinorelbine, are underway at a number of centres. Paclitaxel, vinorelbine and doxorubicin are three of the world`s best-selling cytotoxic drugs. Interim trial results from the doxorubicin study were announced in May 2000 and final PK data from these trials is anticipated for both studies before the end of the current year. The Phase IIa clinical trials programme is being carried out in both the US and UK. Preliminary Phase II pharmacokinetic (PK) data, showing that XR9576 was well tolerated and without PK interaction, was announced in November 1999. IND approval was also received in late November 1999. The successful completion of the XR9576 paclitaxel study and positive interim data from the doxorubicin study were announced in March and May 2000 respectively. In October, a research update from the company showed that XR9576 in its three Phase IIa trials was compatible with other administered drugs such as doxorubicin and Paclitaxel. The third trial, being carried out at the National Cancer Institute in the U.S., is being studied in combination with vinorelbine, another leading cancer drug. It is scheduled for completion by year-end. 2. XR5000 acts as an inhibitor of both topoisomerases I and II, 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. It has demonstrated significant activity in preclinical animal models against several types of solid tumours, including multi-drug resistant cancers. XR5000 completed Phase I studies in late 1998. XR5000 is in three Phase II clinical trials underway at a number of European centres. The drug is a topoisomerase I and II inhibitor for the treatment of common solid tumours. The Phase II trials are being conducted on an `open label` basis and target three cancer types - ovarian, non-small cell lung and glioblastoma. In preclinical studies, XR5000 has been shown to be effective in cases where a tumour has already shown resistance to treatment with existing cytotoxic drugs. The results of a fourth Phase II trial, in which the efficacy of XR5000 was investigated in-patients with colorectal cancer, were announced in June 2000. XR5000 was shown to have a good safety profile. Final data from all three remaining studies are expected to be available during Q4 2000. Results from these trials will help determine the future development strategy for this compound. 3. XR11576 is structurally dissimilar to XR5000, with a significant improvement in its profile including oral bioavailability and a marked enhancement of potency, while retaining certain advantageous characteristics of XR5000. It is essentially a novel, orally active, next generation cytotoxic topoisomerase I and II inhibitor. In preclinical studies, XR11576 has been shown to be highly potent as acytotoxic agent against both parental and MDR cell lines. In vivo it has been shown to inhibit the growth of human and murine tumours after iv and oral administration and to display good potency when compared with competitors` development candidates in the same broad class. The XR11576 series of compounds is protected by a priority patent application in the UK. The drug is undergoing final pharmacological and toxicity testing, prior to its planned entry into clinical development. |
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| aus der Diskussion: | XENOVA - DISKUSSIONS-THREAD Nr. 2 (Stand: 06.11.2000) |
| Autor (Datum des Eintrages): | chaxx999666 (26.01.01 22:46:10) |
| Beitrag: | 23 von 275 (ID:2783826) |
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