London-based leading RNA interference (RNAi) therapeutics company, Silence Therapeutics plc has reported 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 per cent 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 per cent survival benefit over untreated.

To further evaluate the findings, Silence announced 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.”

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 per cent (New England Journal of Medicine 2005; 353:1685-93.)

Silence Therapeutics plc 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.