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17/06/2002

Phase I data for Antisoma’s DMXAA presented at International Conference on Vascular Targeting

London, UK: Prof. Gordon Rustin of Mount Vernon Hospital, Middlesex, UK, has just presented details of the results from two Phase I trials of Antisoma's vascular targeting agent DMXAA. Speaking on Friday at the First International Conference on Vascular Targeting in Cambridge, Mass, Prof. Rustin explained that the drug was well tolerated as monotherapy at doses that reduced tumour blood flow and increased the production of serotonin, effects that have been associated with the anti-tumour activity of the drug in pre-clinical studies.

Antisoma plans to conduct Phase Ib trials with DMXAA in combination with taxanes, carboplatin and other anti-cancer therapies. These plans are supported by the Phase I findings, which showed that DMXAA does not cause neutropenia or other side-effects classically associated with conventional chemotherapies. The lead indication to be investigated will be lung cancer.

The Phase I trials reported by Prof Rustin included 109 patients in the UK and New Zealand, all of whom had advanced-stage cancer, with a wide variety of tumour types represented. Patients received 408 infusions of DMXAA over 19 dose levels from 6 to 4900 mg/m2, where dose-limiting toxicity was defined. Doses below the maximum tolerated dose were generally well tolerated, with mild temporary visual disturbance being the most commonly observed side-effect.

The text of Prof. Rustin's abstract to the Vascular Targeting meeting is reproduced below. Full results of the individual Phase I studies are expected to be published later in peer-review journals.

Commenting on the findings, Glyn Edwards, CEO of Antisoma, said:
'Building on the pre-clinical evidence for synergies between DMXAA and other cancer therapies, these results encourage us to go forward and explore the full potential of DMXAA in patients.'

Enquiries:

Antisoma plc		+44 (0)20 8799 8200
Glyn Edwards, Chief Executive Officer
Financial Dynamics:		+44 (0)20 7831 3113
Jonathan Birt/Ben Atwell

Except for the historical information presented, certain matters discussed in this statement are forward looking statements that are subject to a number of risks and uncertainties that could cause actual results to differ materially from results, performance or achievements expressed or implied by such statements. These risks and uncertainties may be associated with product discovery and development, including statements regarding the company's clinical development programmes, the expected timing of clinical trials and regulatory filings. Such statements are based on management's current expectations, but actual results may differ materially.

Notes to Editors

Abstract submitted by Prof Gordon Rustin to the First International Conference on Vascular Targeting and presented on June 14th 2002:
'Clinical Experience of 5,6-Dimethylxanthenone-4-acetic acid (DMXAA) Gordon J S Rustin, Director of Medical Oncology, Mount Vernon Cancer Centre, Northwood, Middlesex, UK.

Two clinical trials of DMXAA have been carried out for the Phase I/II committee of CRUK using different schedules. Infusions were administered over twenty minutes intravenously every 3 weeks in Auckland, New Zealand and weekly at Mount Vernon and Bradford, UK. In addition to determining toxicity, maximum tolerated dose and pharmacokinetics (PK) of DMXAA, pharmacodynamic endpoints were investigated to discover whether DMXAA had vascular targeting activity in man and to better understand its mechanism of action.

No differences were observed between the two schedules so the results are here combined. 109 patients received 408 infusions of DMXAA over 19 dose levels from 6-4900 mg/m2 , where dose- limiting toxicity (DLT) was defined. This included transient confusion, tremor, slurred speech, visual disturbance, anxiety, urinary incontinence, vomiting, malaise and left ventricular failure. Doses below DLT were generally well tolerated with mild temporary visual disturbance being the most common toxicity. PK were dose dependent and saturation of protein binding at higher doses resulted in a rapid increase in free plasma drug levels. Higher drug concentrations were achieved in human tumors than in mice treated at their maximum tolerated dose (MTD).

Mechanistic endpoints confirmed the vascular targeting activity of DMXAA. Dynamic contrast enhanced MRI (DCE-MRI) was performed on 16 patients at doses from 500-4900 mg/m2. Nine of 16 patients had significant reductions in the area under the signal intensity time curve (AUC) 24 hours after the first dose of DMXAA, and 8 of 11 had reductions of up to 66% in AUC 24 hours after the last dose. AUC in muscle 24 hours after the first dose was significantly reduced, but no significant changes were seen in muscle 24 hours after the last dose. Dose dependent increases in the serotonin metabolite 5-hydroxyindoleacetic acid were observed. No increase in plasma TNF was seen. However tumour biopsies performed on 3 patients in Auckland showed increased local TNF production in one. One patient receiving 1100 mg/m2 DMXAA for cervical carcinoma and one receiving 1300 mg/m2 for melanoma had unconfirmed partial responses.

These results were sufficiently encouraging for Antisoma to license DMXAA so that they can better determine the dose to take into phase 2 trials. It is expected that the major anti-tumour activity will only be see when DMXAA is given as combination therapy.'

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Antisoma
Antisoma is a biopharmaceutical company developing novel products for the treatment of cancer. Using its drug development experience, the Company aims to produce safer and more effective tumour targeting therapies for commercialisation by pharmaceutical partners. Antisoma acquires the rights to promising new product candidates through partnerships with internationally recognised academic or cancer research institutions. These include the lead product candidate, pemtumomab, which was licensed from the Imperial Cancer Research Fund and is currently in a Phase III study as adjuvant treatment for ovarian cancer, with designated Orphan Drug status in the US and EU. There are three additional products in the clinical pipeline, Therex, DMXAA and TheraFab, and an extensive pre-clinical programme. Visit www.antisoma.com for further information about Antisoma.

DMXAA
DMXAA was discovered by Professors Bruce Baguley and William Denny and their teams at the Auckland Cancer Society Research Centre ("ACSRC"), University of Auckland, New Zealand. In extensive pre-clinical studies carried out by the ACSRC, DMXAA, when used in combination with a number of other anti-cancer agents, particularly taxanes, was seen to control the growth of tumours in animal models and, in several cases, to eradicate them. Dose-ranging, Phase I clinical trials, sponsored by the Cancer Research Campaign in the UK and in New Zealand, have provided safety data and indicate that DMXAA causes a reduction in tumour blood flow when used alone. DMXAA was in-licensed by Antisoma from Cancer Research Ventures Limited ('CRV') in August 2001.

Cancer Research Ventures (CRV)
CRV is a technology transfer and development company established by The Cancer Research Campaign in the UK to provide technology transfer services to cancer researchers on a worldwide basis. CRV, and its forerunner CRCT, have been providing these services to UK researchers since 1987 and have recently expanded the business into Europe and further afield through the affiliate company Biotech Research Ventures in Singapore. CRV has been instrumental in establishing a number of successful biotech companies in the UK.