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Antisoma’s AS1404 enhances effectiveness of Avastin in colon and lung cancer models


Washington, DC and London, UK: 3 April 2006 A preclinical data presentation at the American Association of Cancer Research (AACR) yesterday revealed that a combination of Antisoma’s AS1404 and Avastin was considerably more effective than Avastin alone at inhibiting the growth of human colon and lung tumour xenografts. Moreover, combining the two drugs did not cause any observable increase in side-effects.

Avastin has attained blockbuster status as a treatment for metastatic colorectal cancer in combination with standard chemotherapy. Filing to extend its use to advanced non-small cell lung cancer and metastatic breast cancer is expected soon. Use alongside Avastin therefore represents an attractive potential market for AS1404, and an expansion of the opportunity for the drug over and above use in combination with chemotherapies, which is the focus of three ongoing phase II trials.

Colorectal cancer represents a potential large indication for AS1404 that has not yet been targeted in Antisoma’s clinical programme. Lung cancer, by contrast, was the first indication in which a phase II trial of AS1404 was started. This trial evaluates AS1404 as part of a triplet combination with the chemotherapy drugs carboplatin and paclitaxel, and reported promising preliminary data in October 2005. The new data support the possibility that future trials could also evaluate a quadruplet regimen including Avastin as well as AS1404 and the two chemotherapy drugs.

Dr Ursula Ney, Chief Operating Officer of Antisoma, said: “The very striking interaction between AS1404 and Avastin shown by these experiments is a really promising development, pointing to additional possible applications for AS1404, a drug which already has very substantial market potential.”

Details of the findings presented at AACR
AS1404 and Avastin each slowed the growth of colon and lung cancer xenografts when used alone. However, the combination of the two drugs was markedly more effective against both tumours. Mean time taken for tumours to quadruple in size was compared between animals receiving the drugs and untreated controls. For the colon cancer (HT29) xenografts, Avastin added 17 days to tumour quadrupling time and AS1404 added 29; tumours treated with the combination took 40 days longer than controls to quadruple in size. With the lung cancer (A549) xenografts, Avastin added 42 days (vs controls) to the time to reach this threshold and AS1404 added 32; the combination added 79 days.

These findings provide new scientific evidence to support the concept of combining vascular disrupting agents (such as AS1404) that act on established tumour blood vessels with anti-angiogenic drugs (such as Avastin) that inhibit the growth of new vessels into tumours.

AS1404 combinations with chemotherapies
A separate poster presentation also made yesterday highlighted the strong preclinical data supporting the current phase II programme for AS1404. The phase II trials programme includes separate randomised, controlled studies in lung, prostate and ovarian cancers. In animal models representing all three of these cancers, addition of AS1404 to a taxane chemotherapy drug provided clear additional benefit compared with the taxane alone. Cures were seen in some animals receiving AS1404-taxane combinations but not in any of those treated with taxanes alone.

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 for Editors:

Background on AS1404
AS1404 (DMXAA) is a small-molecule vascular disrupting agent which targets the blood vessels that nourish tumours. The drug was discovered by Professors Bruce Baguley and William Denny and their teams at the Auckland Cancer Society Research Centre, University of Auckland, New Zealand. It was in-licensed by Antisoma from Cancer Research Ventures Limited (now Cancer Research Technologies) in August 2001. Preclinical evidence shows that the drug significantly enhances the efficacy of various chemotherapy drugs, complementing their action on tumours. Antisoma’s programme of phase II trials therefore combines AS1404 with established chemotherapy treatments. The programme includes separate randomised, controlled trials in lung, prostate and ovarian cancers. Preliminary findings from the lung cancer trial showed a higher frequency of tumour responses and a lower frequency of progressive disease in those patients receiving AS1404 in addition to chemotherapy.

Background on Antisoma
Based in London, UK, Antisoma is a biopharmaceutical company that develops novel products for the treatment of cancer. Antisoma fills its development pipeline by acquiring promising new product candidates from internationally recognised academic or cancer research institutions. Its core activity is the preclinical and clinical development of these drug candidates. In 2002, Antisoma formed a broad strategic alliance with Roche to develop and commercialise products from Antisoma’s pipeline. AS1404 is one of the products included in this alliance. Please visit for further information.


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