Xenova Group PLC
31 October 2001
For Immediate Release
Xenova Group plc
Cancer Research Update at EORTC/NCI AACR Symposium
Slough, UK, 31st October 2001 - Xenova Group plc (Nasdaq: XNVA; London Stock
Exchange: XEN) today announced the publication of new research data at the
EORTC/NCI AACR Symposium on Molecular Targets & Cancer Therapeutics, currently
being held in Miami Beach, Florida.
Xenova has presented data at the Symposium on recent progress made in Xenova's
anti-angiogenesis and cytotoxic drug research programmes. Data presented
included progress made with Xenova's second generation topoisomerase
inhibitors and a research update for Xenova's plasminogen activator-1 (PAI-1)
inhibition programme. Details of an earlier Phase IIa trial for Xenova's lead
multi-drug resistance modulator candidate, XR9576, were also presented.
Poster: Ex vivo activity of two novel dual topoisomerase I and II inhibitors
XR5944 and XR11576 against solid tumours
The preclinical studies, carried out in conjunction with Professor Ian Cree of
Queen Alexandra Hospital, Portsmouth and UCL, London, UK, were conducted with
biopsy samples taken from 24 ovarian and 27 cutaneous melanoma patients.
Cutaneous melanoma is a tumour generally regarded as resistant to
The data presented demonstrated a more than 20 -fold enhancement of potency
for XR11576 and XR5944, two of Xenova's second generation topoisomerase
inhibitors, relative to a first generation inhibitor (XR5000). XR11576 and
XR5944 have both been developed by Xenova's in-house research function. The
topoisomerase programme has been developed from Xenova's collaboration with
the Auckland Cancer Research Centre. It is anticipated that XR11576 will
enter Phase I/II clinical trials before the end of 2001.
Poster: XR11612, a novel dual inhibitor of topoisomerase I and II with potent
Preclinical data comparing the in vitro efficacy of XR11612, a further novel,
next generation topoisomerase inhibitor, with a number of widely used
cytotoxic drugs have also been presented.
These preclinical studies compared the in vitro efficacy of XR11612 and the
cytotoxic drugs and assessed the degree to which they are affected by the
various types of drug resistance mechanism frequently found in cancer
patients. XR11612 was shown to be unaffected by P-glycoprotein, MRP
(multi-drug resistance protein) or atypical drug resistance mechanisms.
XR11612 also showed significant antitumour efficacy against murine and human
carcinoma models after iv and oral administration. In this study the activity
profile of XR11612 was observed to be equal to or better than a number of
widely used anticancer drugs including doxorubicin and topotecan and also TAS
103, a drug candidate under development by Bristol-Myers Squibb.
Topoisomerase inhibitors comprise a major class of cytotoxic anti-cancer agent
that is widely used to treat cancer patients. 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
Poster: Low molecular weight inhibitors of PAI-1 suppress tumour cell invasion
and angiogenesis in vitro and reduce tumour cell growth in vivo
Evidence has been presented supporting the critical role of PAI-1 in cancer
progression and metastasis, as well as the ability of antibodies and a small
molecule PAI-1 inhibitor (XR5967) to significantly inhibit cell invasion and
In related studies, a second small molecule PAI-1 inhibitor (XR5118) has also
been shown to significantly inhibit tumour growth in a metastatic lung
Xenova is developing its PAI-1 inhibitors as novel inhibitors of angiogenesis.
Angiogenesis is believed to be important in the process of tumour cell
invasion, migration and metastasis. Angiogenesis inhibitors have shown
promise in preclinical studies in inhibiting tumour cell migration, invasion
Xenova has a collaboration with Lilly for the development of Xenova's PAI-1
inhibitors for use in cardiovascular disease. Lilly also has an option to
acquire rights to Xenova's PAI-1 inhibitors for use in cancer.
Multi-drug resistance modulation programme
Poster: The novel P-glycoprotein (P-gp) antagonist, XR9576, in combination
with vinorelbine, has no effect on the pharmacokinetics of the cytotoxic drug
Results from a previously reported Phase IIa study multi-drug resistance
modulator XR9576 (tariquidar) were additionally presented. XR9576 was given
in combination with vinorelbine in a study conducted by the National Cancer
Institute (USA). The study found that a 150mg dose of XR9576 (tariquidar) did
not significantly affect the pharmacokinetic parameters of vinorelbine when
given at up to 22.5mg/m(2) and demonstrated that a vinorelbine dose of 20mg/m
(2) can be safely administered in combination with a single 150mg dose of
XR9576 (tariquidar) in a heavily pre-treated group of patients. XR9576 has
also successfully completed further Phase IIa combination studies with the
cytotoxic drugs doxorubicin and paclitaxel.
Xenova signed an agreement for the development and North American marketing of
XR9576 with QLT Inc in August 2001. It is anticipated that XR9576 will enter
Phase III clinical trials in the first half of 2002.
Xenova Group plc Financial Dynamics
Tel: +44 (0) 1753 706600 Tel: +44 (0) 207 831 3113
David Oxlade: Chief Executive Officer David Yates/Fiona Noblet
Daniel Abrams: Finance Director
Hilary Reid Evans: Corporate Communications
Tel: 001 212 477 9007
Brad Miles (Ext 17)/Lauren Tortorete (Ext 20)
Notes to Editors
Xenova's product pipeline focuses principally on the therapeutic areas of
cancer, infectious, autoimmune and cardiovascular diseases. The Group has a
well-established track record in the identification, development and
partnering of innovative products and technologies. Xenova has partnerships
with a number of major pharmaceutical companies including Lilly, Pfizer,
Celltech and QLT Inc.
For further information about Xenova and its products please visit the Xenova
website at www.xenova.co.uk.
Safe Harbor Statement under the US Private Securities Litigation Reform Act of
1995: Some or all of the statements in this document that relate to future
plans, expectations, events, performances and the like are forward-looking
statements, as defined in the US Private Securities Litigation Reform Act of
1995. Actual results of events could differ materially from those described
in the forward-looking statements due to a variety of factors, including those
set forth in the Company's filings with the US Securities and Exchange