Quantcast
Last updated on April 20, 2014 at 14:04 EDT

Significant Pre-Clinical Data in Acute Lung Injury

September 9, 2012

LONDON, September 10, 2012 /PRNewswire/ –

Silence Therapeutics plc [http://silence-therapeutics.com ] (AIM: SLN) (“Silence” or
“the Company”), a leading RNA
[http://silence-therapeutics.com/content/therapeuticplatform/overview.htm ] 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(TM),
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(TM). 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.

        Silence Therapeutics
        Ali Mortazavi (+44(0)7768-694739 /Jerry Randall (+44(0)7990-502000)
        Email: a.mortazavi@silence-therapeutics.com, j.randall@silence-therapeutics.com

        Singer Capital Markets
        Shaun Dobson/Claes Spang
        +44(0)20-32057500
        shaun.dobson@singercm.com
        claes.spang@singercm.com

        M:Communications
        Mary-Jane Elliot / Sarah MacLeod /
        Claire Dickinson
        +44(0)20-7920-2342
        silencetherapeutics@mcomgroup.com

SOURCE Silence Therapeutics Plc


Source: PR Newswire