Tumour-Vascular Disrupting Agent, ASA404

[Rich66]

London, UK, and Cambridge, MA, 12 February 2009 - Antisoma plc (LSE: ASM; USOTC:ATSMY) announces that its Tumour-Vascular Disrupting Agent, ASA404, will be evaluated by Novartis as a treatment for HER2-negative metastatic breast cancer. This indication is being prioritised ahead of prostate cancer, in which a phase II trial has been completed. Details of the plans for trials in breast cancer will be available later this year.
Antisoma and Novartis have a worldwide development and commercialisation agreement for ASA404. Trials in breast cancer will be in addition to two ongoing pivotal phase III trials in patients with non-small cell lung cancer, one (ATTRACT-1) testing ASA404 as a first-line treatment and the other (ATTRACT-2) evaluating ASA404 as a second-line treatment. Because ASA404 acts by disrupting tumour blood vessels, it has potential application against a variety of solid tumours, all of which depend on tumour blood vessels to survive and grow.
Glyn Edwards, Antisoma's CEO, said: "We are very pleased that Novartis is extending the development of ASA404 to metastatic breast cancer. This represents a significant additional opportunity for ASA404. While there have been many advances in the treatment of breast cancer, there remains a great need for new and innovative approaches, especially for patients with metastatic cancer."
About metastatic breast cancer
Worldwide, more than a million women are diagnosed with breast cancer and over 400,000 die from the disease each year. Metastatic breast cancer is the most advanced stage (stage IV). Over 100,000 patients present with stage IV disease each year in the US, Europe and Japan.
About ASA404
ASA404 (DMXAA) is a small-molecule Tumour-Vascular Disrupting Agent (Tumour-VDA) which selectively 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 Technology), the development and commercialisation company of the Cancer Research Campaign (now Cancer Research UK), in August 2001. In a randomised phase II study in non-small cell lung cancer, addition of ASA404 to standard first-line chemotherapy was associated with a 5 month improvement in median survival. Worldwide rights to the drug were licensed to Novartis AG in April 2007.
About Antisoma
Antisoma is a London Stock Exchange-listed biopharmaceutical company that develops novel products for the treatment of cancer. The Company has operations in the UK and the US. Please visit www.antisoma.com for further information about Antisoma.
Enquiries:


Glyn Edwards, CEODaniel Elger, VP, Marketing & Communications +44 (0)7909 915 068Antisoma plcMark Court/Lisa Baderoon/Rebecca Skye +44 (0)20 7466 5000DietrichBuchanan CommunicationsBrian Korb +1 646 378 2923The Trout Group
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

[Rich66]

This article for historical reference 11/04/2008, 07.15 AM CET

ASA404, a novel cancer agent, begins pivotal trial to explore new approach in treating lung cancer, the leading cause of cancer death

With launch of Phase III ATTRACT-1 trial in non-small cell lung cancer, Novartis Oncology assumes responsibility for development of ASA404 from Antisoma Novel mechanism of action of ASA404 disrupts existing blood supply to tumors Tumor-Vascular Disrupting Agent is one of six Novartis Oncology compounds in late-stage development for various solid tumors and blood cancers With launch of Phase III ATTRACT-1 trial in non-small cell lung cancer, Novartis Oncology assumes responsibility for development of ASA404 from Antisoma Novel mechanism of action of ASA404 disrupts existing blood supply to tumors Tumor-Vascular Disrupting Agent is one of six Novartis Oncology compounds in late-stage development for various solid tumors and blood cancers Basel, April 11, 2008 -Novartis announced today that ASA404, its novel cancer agent, has entered a Phase III lung cancer trial following positive outcomes of a Phase II trial. The novel mechanism of action of ASA404 may represent a new approach to treating the most prevalent cause of cancer death. ASA404 is a Tumor-Vascular Disrupting Agent (Tumor-VDA) that selectively causes the collapse of existing tumor blood supply leading to extensive tumor cell death. The action of ASA404 is distinct from that of angiogenesis inhibitors, which inhibit the formation of new tumor blood vessels. In a randomized Phase II study, ASA404, in combination with chemotherapy, demonstrated a median overall survival advantage of more than five months in first-line treatment of advanced non-small cell lung cancer (NSCLC) compared with chemotherapy alone. A similar survival advantage was observed in a subsequent extension of the Phase II study. Non-small cell lung cancer, the potential lead indication for ASA404, accounts for about 85% to 90% of all lung cancers. Worldwide, lung cancer is the number one cause of death from cancer each year in both men and women, with 1.2 million new cases per year and 921,000 deaths. "With the launch of ATTRACT-1, we look forward to exploring the unique mechanism of action of ASA404 in non-small cell lung cancer to potentially help the more than one million people who develop lung cancer each year," said Alessandro Riva, Executive Vice President and Global Head of Development of Novartis Oncology. ASA404 is one of six novel oncology compounds Novartis is developing for potential registration over the next five years.The other investigational therapies which focus on a broad array of cancer targets include RAD001 (renal cell carcinoma and other cancers), SOM230 (Cushing's disease/refractory carcinoid tumors, acromegaly), LBH589 (cutaneous T-cell lymphoma and other cancers), EPO906 (ovarian cancer), and PKC412 (acute myelogenous leukemia and aggressive systemic mastocytosis). "Today, our broad and deep pipeline includes both small molecules and monoclonal antibodies that utilize a variety of mechanisms such as vascular-disruption, anti-angiogenesis, and kinase inhibition to treat cancer," said David Epstein, President and CEO of Novartis Oncology. "These exciting potential discoveries have the possibility to change medical treatment for patients suffering with many forms of cancer." About ATTRACT-1 ATTRACT-1 (Antivascular Targeted Therapy: Researching ASA404 in Cancer Treatment) is a Phase III clinical trial that will be conducted at more than 200 sites in 20 countries. The trial will be a randomized, double-blind, placebo-controlled, multi-center study of ASA404 in combination with paclitaxel and carboplatin as first-line treatment for locally advanced or metastatic (Stage IIIb/IV) NSCLC of squamous or nonsquamous histology. The trial will consist of 1,200 patients who will be assigned to one of the following treatment arms in a ratio of 1:1: ASA404 1800 mg/m2 plus chemotherapy (carboplatin/paclitaxel) or placebo plus chemotherapy (carboplatin/paclitaxel) as a control. Treatment will be given for up to six cycles, with one cycle equaling 21 days and total treatment equaling 126 days (4.2 months). ASA404 ASA404 is a small-molecule Tumor-VDA that selectively disrupts existing tumor blood vessels. Solid tumors rely on a network of blood vessels to survive and grow. ASA404 targets existing tumor blood vessels causing death of vessel endothelial cells and the collapse of tumoral blood vessels. Novartis signed an exclusive licensing agreement with Antisoma plc for the worldwide rights to ASA404 in April 2007.

[Rich66]

ASA404 (DMXAA, formerly AS1404)




ASA404 (DMXAA) is a small-molecule Tumour-Vascular Disrupting Agent (Tumour-VDA) that selectively disrupts established tumour blood vessels. It is currently in phase III clinical trials for lung cancer and will enter trials in breast cancer later in 2009. Antisoma has licensed the world-wide rights for ASA404 to Novartis AG. Novartis is now responsible for all further development work on the drug.


Targeting established tumour blood vessels


Solid tumours rely on a network of blood vessels in order to survive and grow. ASA404 targets established tumour blood vessels causing apoptosis (death) of tumour endothelial cells and the local release of vasoactive molecules including tumour necrosis factor (TNF) and nitric oxide. This results in rapid reduction in blood flow to the tumour, leading to tumour necrosis. The action of ASA404 is distinct from that of angiogenesis inhibitors, which inhibit the formation of new tumour blood vessels.

Latest presentations Lung cancer poster presentation at ASCO, 2008 (PDF, 111 KB, opens a new browser window) Prostate cancer slide presentation at ASCO, Chicago 2008 (PDF, 539 KB, open a new browser window) Lung cancer poster presentation at WCLC, 2007 (PDF, 152 KB, opens a new browser window) Lung cancer poster presentation t AACR-NCI-EORTC Prague 2006 (PDF, 52 KB, opens a new browser window) Prostate cancer poster presentation at ASCO Chicago 2007 (PDF, 100 KB, opens a new browser window) Ovarian cancer poster presentation at ECCO Barcelona 2007 (PDF, 126 KB, opens a new browser window)

Potential in combination with other cancer treatments

The therapeutic potential of ASA404 lies in combination with cytotoxic agents and other cancer treatments. Preclinical tests have shown synergistic (more than additive) effects with such combinations, and they have now become the focus for human clinical trials. Antisoma has conducted phase II trials with ASA404 in combination with standard chemotherapy in lung, prostate and ovarian cancers.
Lung cancer - the lead indication for ASA404

The lead indication for ASA404 is non-small cell lung cancer. Novartis is conducting two pivotal phase III trials in this indication, which will build on supportive data from phase II studies carried out previously by Antisoma, as described below.
A randomised phase II study in lung cancer included patients with stage IIIb/IV non-small cell lung cancer of any histology (NCT00832494). Median survival was 14.0 months in patients receiving ASA404 plus carboplatin and paclitaxel chemotherapy, compared with 8.8 months in patients receiving chemotherapy alone. Addition of ASA404 to chemotherapy was generally well tolerated.
A single-arm study was conducted as an extension to the phase II trial. This also included non-small cell lung cancer patients with stage IIIb or IV disease of any histology. In this study, an 1800mg/m²; dose of ASA404 was combined with carboplatin and paclitaxel (whereas all the randomised studies in lung and other cancers used a 1200mg/m² dose). Median survival was 14.9 months.
Data from these phase II studies show that patients with both squamous and non-squamous types of non-small cell lung cancer experienced a survival benefit with ASA404.