SLN.L Regulatory News (SLN)

1 Dec 2008 07:00

Silence Therapeutics publishes comprehensive research showing that its lead

candidate Atu027 inhibits cancer progression

London - 1 December 2008 - Silence Therapeutics plc (AIM: SLN), the leading European biopharmaceutical company focused on RNA interference, announces today that the journal Cancer Research has published results of a study of Atu027 conducted in collaboration with Charitĩ, Campus Virchow Hospital, University Medicine Berlin.

The paper presents comprehensive pre-clinical data on Atu027, which is being developed by Silence Therapeutics as a drug product for the treatment of solid tumours. The highlights of the findings are that Atu027 was functionally delivered and effective at gene silencing over the 28 day course of treatment, resulting in the successful inhibition of tumour progression. Atu027 is a small interfering RNA (siRNA) lipoplex.This is the first time that multiple doses of a lipoplex formulated siRNA molecule have been administered to non-human primates over a 28 day period.

Professor Bertram Wiedenmann, Director of the Department of Hepatology and G astroenterology at the Charitƒ©-Universitƒ¤tsmedizin Berlin,Campus Virchow -Klinikum,Berlin, said:

"Existing experimental data favours Atu027 as a new, very promising class of cancer agents for the treatment of solid tumours. Given its efficacy in animal models combined with its final clinical trial application approval, Silence will be in a position to enter the clinic with the drug product candidate that can be administered in multiple doses."

Iain Ross, Chairman and Chief Executive of Silence Therapeutics said

"These results not only represent a significant advance for Silence Therapeutics, but also for the entire field of RNA interference. Silence Therapeutics and its collaborators at University Medicine Berlin have evidence that validates both our lead product, Atu027, and our AtuPLEX delivery platform."

In a multiple dose trial in models of prostate and pancreatic cancer, researchers found evidence that Atu027 is effective in the significant inhibition of tumour growth and metastasis. The study also demonstrated a dose-dependent effect.

Atu027 is being developed for the treatment of advanced solid cancers and is scheduled to enter clinical trials in 2009. Atu027 is a lipid-based formulation of a siRNA molecule which targets protein kinase N3 (PKN3), Silence's proprietary target for cancer therapeutics.

In the pre-clinical trials discussed in Cancer Research, Atu027 was administered systemically by repeated injections or infusions in three species, including non-human primates. The paper - Atu027, a Liposomal Small Interfering RNA Formulation Targeting Protein Kinase N3, Inhibits Cancer Progression - is published today and can be found at http://cancerres.aacrjournals.org/. Cancer Research is a peer-reviewed publication of the American Association of Cancer Research.

Researchers conducted trials of a novel lipoplex formulation of Atu027 which offers improved pharmacokinetic properties, cellular uptake and efficient release. Systemic administration of Atu027 by repeated bolus injections or infusions resulted in the suppression of PKN3 expression in vascular endothelial cells.

The trial also examined the potential of Atu027 to inhibit metastasis, recognising that an estimated 90% of deaths associated with solid cancers are due to metastases. This part of the study demonstrated in pre-clinical models additional evidence of the pharmacologic activity of Atu027. As the Cancer Research paper reports, researchers observed that "repeated dosing every fourth day resulted in a significant inhibition of further tumour growth and lymph node metastasis formation in animals. At the same time, no signs of toxicity or other adverse effects were observed over the entire treatment period, as indicated by the maintenance of stable bodyweight.

Ends

Enquiries:

For further information, please contact the following:

Silence Therapeutics plc

Klaus Giese, Chief Scientific Officer and Vice President Research

+49 30 9489 2800Powerscourt+44 (0) 20 7250 1446Paul DurmanKay LarsenNominated Advisers

Nomura Code Securities Limited

+44(0)20 7776 1200

Chris Collins

About Silence Therapeutics plc (www.silence-therapeutics.com)

Silence Therapeutics plc (AIM: SLN) is a leading European RNAi focused biotechnology company.

RNA interference (RNAi) is a Nobel Prize winning technology and one of the most exciting areas of drug discovery today. It represents a completely new approach to selectively 'silence' or inactivate disease relevant genes and as such it has the potential to create a new class of therapeutic products. RNAi could therefore offer a therapeutic approach to a broad range of diseases (cancer, infectious diseases, inherited diseases), many of which have been regarded as incurable and are not addressed by current therapeutics, therefore providing a large market opportunity.

Silence Therapeutics has developed a platform of novel short interfering RNA ('siRNA') molecules, AtuRNAi, which provide a number of advantages over conventional siRNA molecules, including increased stability against nuclease degradation. In addition, the Company has developed a proprietary systemic delivery platform, AtuPLEX. This platform enables the functional delivery of siRNA molecules to targeted diseased tissues and cells, while increasing their bioavailability and intracellular uptake.

Following the granting of its patents in Europe, Australia and the USA, Silence Therapeutics is one of only two companies worldwide with a proprietary position on composition of matter for siRNA therapeutics.

Silence's lead internal product, Atu027, is a proprietary AtuRNAi molecule in preclinical development for systemic cancer indications. Atu027 has successfully completed single and repeat dose toxicology and geno-toxicology studies, as well as a 28-day toxicology study using multiple dosing regimens. Silence plans a regulatory filing in 2008 to commence clinical trials for Atu027.

In March 2008 Silence Therapeutics announced a collaboration with AstraZeneca focused on the development of a range of novel delivery approaches for siRNA molecules. Under the terms of the agreement both Silence Therapeutics and AstraZeneca will be allowed to commercialize the truly novel delivery systems that the two partners develop together.

Silence Therapeutics has granted a licence to AstraZeneca to develop novel AtuRNAi therapeutics against five specific targets, including those in respiratory indications. This collaboration was the first industry validation of the potential application of Silence Therapeutics' proprietary AtuRNAi molecules and solidified the Company's leadership position in field of RNAi therapeutics.

The Company's AtuRNAi technology also has been sublicensed to Pfizer via Quark's license to them of the compound RTP-801i-14 for the treatment of age-related macular degeneration (AMD) and a number of other indications. This compound entered a phase II clinical study in July 2008. Silence Therapeutics also has licensed to Quark rights to the AtuRNAi structure for Quark's proprietary compound, AKIi-5, which is in a Phase I human clinical study for treatment of acute kidney injury.

Silence Therapeutics is based in London, UK, and Berlin, Germany, and is listed on AIM.

Forward-Looking Statements

This press release includes forward-looking statements that are subject to risks, uncertainties and other factors. These risks and uncertainties could cause actual results to differ materially from those referred to in the forward-looking statements. All forward--looking statements are based on information currently available to Silence Therapeutics and Silence Therapeutics assumes no obligation to update any such forward-looking statements.