Significant Pre-Clinical Data in Acute Lung Injury Proof of Concept Study in Well-Accepted Pre-Clinical Model Shows 90% Survival Benefit with Atu111 in Combination With Antibiotics
LONDON, September 10, 2012 /PRNewswire/ --
Silence Therapeutics plc (AIM: SLN) ("Silence" or "the Company"), a leading RNA interference (RNAi) therapeutics company is pleased to announce that recent data in pre-clinical models demonstrated the efficacy of Atu111 in acute lung injury. Atu111 targets the endothelial expression of Angiopoietin-2 (Ang-2), an antagonistic ligand of Tie-2 signalling, which is implicated in progressing endothelial dysfunction in the context of disease pathogenesis for acute lung injury or sepsis.
The study, which evaluated the use of Atu111 in a preclinical Streptococcus pneumoniae model of acute lung injury, was conducted by Ricerca Biosciences, a US-based clinical research organisation. The trial demonstrated a 90% survival benefit with the use of Atu111 in the presence of antibiotics when compared to an untreated control cohort. By contrast, antibiotic therapy alone achieves only a 20% survival benefit over untreated.
To further evaluate the findings, Silence is pleased to announce the successful start of a research alliance with the laboratory of Prof. Dr. med. Hermann Haller, Director of Nephrology and Chairman of the Department of Internal Medicine at the Medizinische Hochschule Hannover MHH (Hannover Medical School, Germany) to evaluate the therapeutic potential of Atu111 in preclinical models for acute lung injury and sepsis. In collaboration with Dr. Sascha David, lead investigator in this project, Atu111, a novel RNAi therapeutic drug candidate based on Silence´s proprietary DACC formulation will be investigated in various pre-clinical models assessing the therapeutic value of Atu111 treatment on inhibiting progression of acute lung injury or sepsis.
A first proof-of-concept with Atu111 in a model for septic/systemic shock revealed superior survival in the Atu111 cohort over an unrelated control formulation. This initial result laid the foundation for the projected systematic investigations addressing the full pharmacological and pharmacodynamic understanding of Atu111 in models of this devastating disease.
Sascha David, MD, stated "Given the high incidence and mortality of sepsis and septic shock in the clinic, specific therapies are highly desirable and Atu111 could represent a very promising candidate. We successfully tested the Atu111 in our murine sepsis model and we are thrilled by the convincing therapeutic and long-lasting gene suppressive effect of the Atu111 compound."
Ali Mortazavi, director of corporate strategy, commented: 'We were already pleased by the results from Ricerca and the support from Hannover confirms our excitement. Atu111 has serious potential for Silence Therapeutics.'
Notes for editors
DACC and Atu111
The DACC drug delivery system used by Atu111 is a lipid-based formulation which is designed to tackle lung-specific diseases. Delivered by blood infusion, the DACC particles become trapped in the small blood vessels of the lungs.
In the US, acute lung injury (principally pneumonia) affects 78.9 per 100,000 persons/year and has an in-hospital mortality rate of 38.5% (New England Journal of Medicine 2005; 353:1685-93.)
About Silence Therapeutics plc (http://www.silence-therapeutics.com)
Silence Therapeutics plc (AIM: SLN) is a leading biotechnology company dedicated to the discovery, development and delivery of targeted, systemic RNA interference (RNAi) therapeutics for the treatment of serious diseases. Silence offers one of the most comprehensive short interfering RNA (siRNA) therapeutic platforms available today based on a strong intellectual property portfolio and large clinical safety database. Silence's clinical siRNA product pipeline is one of the broadest in the industry. The Company possesses multiple proprietary siRNA delivery technology platforms including AtuPLEX™, DACC and DBTC. AtuPLEX enables the broad functional delivery of siRNA molecules to targeted diseased tissues and cells, while increasing their bioavailability and intracellular uptake. The DACC delivery system allows functional delivery of siRNA molecules selectively to the lung endothelium with a long duration of target mRNA and protein knock-down. The DBTC delivery system enables functional delivery of siRNA molecules selectively to liver cells including hepatocytes. Additionally, the Company has a platform of novel siRNA molecules based around its AtuRNAi chemical modification technology, which provides a number of advantages over conventional siRNA molecules. Silence's unique RNAi assets also include structural features for RNAi molecules and specific design rules for increased potency and reduced off-target effects of siRNA sequences.
The Company's lead internal drug candidate is Atu027, a liposomal formulation in clinical development for systemic cancer indications and one of the most clinically advanced RNAi therapeutic candidates in the area of oncology. Atu027 incorporates two of the Company's technologies, AtuRNAi and AtuPLEX™. Silence is currently conducting an open-label, single-centre, dose-escalation Phase I study with Atu027 in patients with advanced solid tumors involving single, as well as repeated, intravenous administration. Encouraging interim safety and pharmacokinetic data were presented at the American Society of Clinical Oncology Annual Meeting in June 2011. The study is expected to be completed in the first half of 2012.
The Company's RNAi therapeutic platform has received key validation through multiple partnerships with pharmaceutical companies including AstraZeneca, Dainippon Sumitomo, Pfizer/Quark, and Novartis/Quark. Silence is actively pursuing the establishment of additional partnerships. Silence Therapeutics has operations in both Berlin and London.
Ali Mortazavi (+44(0)7768-694739 /Jerry Randall (+44(0)7990-502000)
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