Antisoma plc (UK) - AACR presentations highlight potential of Antisoma drugs AS1413 and AS1411
London, UK, Cambridge, MA, and Washington, DC: 19 April 2010 - Antisoma plc (LSE:ASM; USOTC:ATSMY) announces that its scientists and collaborators are presenting six posters on AS1413 (amonafide L-malate) and AS1411 this week at the annual meeting of the American Association for Cancer Research in Washington, DC. The presentations highlight the distinctive features and potential of these two novel cancer drugs, both of which are in advanced clinical testing.
Glyn Edwards, CEO of Antisoma, said: "AS1413 and AS1411 are both un-partnered products with significant commercial potential. The latest data on AS1413 reinforce the clear differentiation of this drug from current leukaemia treatments and its potential to offer unique benefits to patients."
AS1413 interferes with the replication of DNA prior to cancer cell division. The drug does this by preventing the enzyme Topoisomerase II (TopoII) from binding to DNA. One presentation shows how this action differs from that of classical TopoII inhibitors, a widely used class of cancer therapeutics. It demonstrates that AS1413 retains activity in leukaemia cells resistant to classical TopoII inhibitors. Antisoma is conducting a phase III trial of AS1413 in patients with secondary acute myeloid leukaemia (secondary AML), a disease where drug resistance is common. The trial compares AS1413-based treatment with standard current treatment based on the classical TopoII inhibitor daunorubicin.
A presentation on AS1411 demonstrates anti-tumour effects in a rat xenograft model of colorectal cancer. This adds to previous data from lung and renal cancer xenografts and data from cell lines representing many types of cancer. The findings are consistent with broad potential of AS1411 across solid and blood cancers.
Effects of AS1411 in an AML cell line are described in a further presentation. AS1411 killed leukaemia cells, and a combination of AS1411 with cytarabine produced synergistic (more than additive) anti-cancer effects. This drug combination is being evaluated in an ongoing phase IIb trial in patients with AML. Other experiments demonstrated synergistic effects of combinations between AS1411 and two of the newer approved products for treatment of blood cancers, decitabine and clofarabine.
Three posters from collaborators provide new data on the mechanisms by which AS1411 exerts its anti-cancer effects. Further details of all the presentations are provided below and on the AACR website at www.aacr.org. Enquiries: Glyn Edwards, CEO
Daniel Elger, VP, Marketing & Communications
+44 (0)7909 915 068
Mark Court/Lisa Baderoon/Catherine Breen
+44 (0)20 7466 5000
+1 646 378 2923
The 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 differ materially. Details of the AACR presentations AS1413
* #3665 The novel DNA intercalator amonafide (AS1413) disrupts the cell cycle by mechanisms distinct from topo II inhibitors daunorubicin and etoposide (Senderovich et al.) Tuesday, 20 Apr 2010, 9am-12pm; Exhibit Hall A-C, Poster Section 27
* #3647 Gene expression analysis in AML cell line MV4-11 following treatment with the anti-cancer aptamer AS1411 (Senderovich et al.) Tuesday 20 Apr 2010, 9am-12pm; Exhibit Hall A-C, Poster Section 27 * #2614 Anti-tumor efficacy and pharmacokinetics of the novel aptamer AS1411 in a continuous infusion nude rat xenograft model (Green et al.) Monday 19 Apr 2010, 2-5pm; Exhibit Hall A-C, Poster Section 25 * #4450 A new paradigm for AS1411 activity: Uptake by macropinocytosis and induction of macropinocytosis by a nucleolin-dependent mechanism (Reyes-Reyes et al.) Tuesday 20 Apr 2010, 2-5pm; Exhibit Hall A-C, Poster Section 23 * #4455 Differential response to AS1411 in a pair of VHL-positive and VHL-negative renal carcinoma cell lines (Islam et al.) Tuesday 20 Apr 2010, 2-5pm; Exhibit Hall A-C, Poster Section 23 * #3642: AS1411 causes a specific increase in levels of cell surface nucleolin in responsive cell lines (Teng et al.) Tuesday 20 Apr 2010, 9am-12pm; Exhibit Hall A-C, Poster Section 27
A number of abstracts relating to ASA404 are also being presented at the meeting. Abstracts for all the presentations and details of their timings/location are available at www.aacr.org<http://www.aacr.org/>
AS1413 (amonafide L-malate) is a DNA intercalator that induces apoptotic signalling by blocking Topoisomerase II binding to DNA. This differs from the action of classical Topoisomerase II inhibitors, which induce apoptosis by causing extensive DNA damage. A further distinctive feature of AS1413 is its ability to evade Pgp and related transporters responsible for multi-drug resistance (MDR). Patients with secondary AML often have multi-drug resistant disease. In an 88-patient phase II trial, the combination of AS1413 and cytarabine produced a 38.6% CR rate in patients with secondary AML. The same regimen is being compared with daunorubicin plus cytarabine in a pivotal randomised phase III trial, ACCEDE, which is expected to report data in late 2010 or early 2011. About AS1411
AS1411 is a DNA aptamer. Aptamers are short pieces of DNA or RNA that assume a specific three-dimensional shape capable of highly specific targeting. AS1411 binds to nucleolin, a protein expressed in the nucleus of all cells but which in cancer cells is also found on the cell surface. When AS1411 binds to nucleolin on cancer cells, it is internalised and causes apoptosis through interference with various functions of nucleolin. AS1411 was originally developed by Dr Paula Bates, Dr John Trent and Prof. Donald Miller at the University of Alabama and then at the University of Louisville. Antisoma added AS1411 to its pipeline when it acquired the Louisville-based company Aptamera Inc. in February 2005. Data from a randomised phase II trial combining AS1411 with cytarabine in patients with AML have provided evidence of activity, and a phase IIb trial is now ongoing in the same setting.
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<http://www.antisoma.com/> for further information about Antisoma.
Posted: April 2010