Antisoma announces positive interim data from AS1411 phase II trial in acute myeloid leukaemia

Study reported at ASH is first randomised trial of an aptamer in cancer

A webcast and conference call about the ASH presentations on AS1411 and AS1413 will be held today at 9am GMT. The webcast can be accessed via Antisoma’s website at www.antisoma.com and the calls by dialling +44 (0)20 8609 1435 (UK toll-free 0808 109 1498; US toll-free 1866 793 4279) and using the participant PIN code 965983#. A recording of the webcast will also be available afterwards on the Antisoma website. A separate press release will be made tomorrow regarding data on AS1413.

London, UK, Cambridge, MA, and San Francisco, CA: 8 December 2008 – Cancer drug developer Antisoma plc (LSE: ASM; USOTC: ATSMY) announces that positive data from an ongoing phase II study of AS1411 in relapsed and refractory acute myeloid leukaemia (AML) were presented this weekend at the American Society of Hematology (ASH) meeting in San Francisco. This study is the first randomised controlled trial to test an aptamer – a new type of drug made of folded DNA or RNA – as a treatment for cancer.

Complete data are now available from the first stage of the trial, in which patients were randomised 1:2 to receive high-dose cytarabine alone (standard therapy control group) or high-dose cytarabine plus AS1411 at 10 mg/kg/day. All patients entering the trial had relapsed after prior treatment or failed to respond to treatment, so few responses were expected. Accordingly, there were no responses in the control group (0/9 patients). By contrast, the response rate in the AS1411 group was 16% (3/19 patients).

As well as the three ‘objective responses’ (two CRs and one CRp) seen in the AS1411 group, a fourth patient in this group demonstrated a cytogenetic response. Additional supportive findings came from a ‘cross-over’ element in the trial, under which control group patients who failed to respond to cytarabine were given the opportunity to receive a further course of treatment with cytarabine plus AS1411. Three patients underwent cross-over treatment, one of whom experienced a 90% reduction in leukaemic blast count after receiving the AS1411 regimen.

AS1411 was well tolerated by patients treated in the first stage of the trial. No severe side-effects were attributed to the drug, and there was no evidence that AS1411 exacerbated the toxicity of high-dose cytarabine.

Commenting on the findings, Dr Robert Stuart of the Medical University of South Carolina, an investigator in the phase II trial and the presenter of the data at the ASH meeting, said: “Given the very poor prognosis of these AML patients, as exemplified by the lack of any responses in the standard-therapy control group, the lack of toxicity and pattern of responses emerging with AS1411 is really encouraging.”

Enrolment has now been completed in the second stage of the trial, which has randomised around 30 more patients 1:2 to receive high-dose cytarabine or high-dose cytarabine plus AS1411 at 40 mg/kg/day (a four-fold higher dose than in the first stage). Final results are expected to be available in the first half of 2009.

Glyn Edwards, Antisoma’s CEO, added: “We have now seen evidence of activity with AS1411 in patients with hard-to-treat leukaemia and advanced renal cancer. This supports non-clinical data suggesting that the drug has potential across a wide variety of blood and solid cancers.”

A copy of the poster presented at the ASH meeting is available on the Antisoma website at www.antisoma.com.

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.

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.

A 30-patient phase I trial provided evidence for activity of AS1411 monotherapy. Among 12 patients with renal cancer, two showed objective responses and seven further patients had a best overall response of stable disease. No serious adverse events related to treatment were observed.

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.

About the AS1411 AML phase II study
The phase II trial randomises patients to three groups: high-dose cytarabine alone; high-dose cytarabine plus 10 mg/kg/day AS1411; and high-dose cytarabine plus 40 mg/kg/day AS1411. Cytarabine is given at 1.5 g/m2 every 12 hours for 4 days (i.e. a total dose of 12 g/m2). AS1411 is given as a continuous 7-day infusion. AS1411 infusion is initiated 3 days before cytarabine treatment so that the administration of the two drugs finishes on the same day.

Randomisation to the two AS1411 groups is sequential. In the first stage of the trial, patients were randomised to cytarabine or cytarabine plus the lower dose of AS1411. In the trial’s second stage, patients have been randomised to cytarabine or cytarabine plus the higher dose of AS1411.

About AML (acute myeloid leukaemia)
AML is a type of cancer in which the bone marrow makes abnormal and immature blood cells, eventually leading to bone marrow failure. The American Cancer Society estimates that there will be over 13,000 new cases of AML diagnosed this year in the US alone.

About response terminology
In the AS1411 phase II trial, responses to treatment (CR or CRp) were defined using the standard approach applied in leukaemia studies (Cheson, BD et al. J. Clin. Oncol. 2003; 21:4642-9). A CR (complete response) requires the disappearance of all signs of leukaemia (with the bone marrow containing fewer than 5% blast cells). A CRp is recorded when all criteria for a CR are met but the patient’s platelet counts do not fully recover.

One patient in the AS1411 group who did not have a CR or CRp had a ‘cytogenetic response.’ This means that the specific chromosomal abnormalities detected at diagnosis were no longer apparent after treatment.

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.