SLN.L Regulatory News (SLN)

7 Apr 2008 07:01

Silence Therapeutics PLC07 April 2008 Recent siRNA Research Publications Support Silence Therapeutics Combined Development Approach Delivery Systems and Specific Molecular Structures Needed for siRNA Therapeutic Success London, 7th April 2008 - Silence Therapeutics plc (AIM:SLN) Europe's leadingRNAi-focused biotechnology company, today comments on two recent journalarticles: Nature1 "Sequence-and target-independent angiogenesis suppression bysiRNA via TLR3" Mark E. Kleinman, et. al., and Molecules and Cells2 "ImmuneActivation by siRNA/Liposome Complexes in Mice is Sequence-Independent: Lack ofa Role for Toll-like Receptor 3," Kim et. al. In these two publications,researchers questioned current thinking on the mode of action of siRNAtherapeutics suggesting that they work by mechanisms other than via specificgene silencing. Data published in the Nature article (Kleinman et. al.) have been interpreted inrecent days in the lay press as a "Setback for Some RNA-Based Drugs" (New YorkTimes5). Silence Therapeutics views the cited Nature paper, and another recentpaper in Molecules and Cells2 as highlighting the need for a functional deliverysystem to ensure the therapeutic siRNA is able to enter cells and achieve genesilencing. Both studies further reinforce the importance of chemically modifying siRNA tocreate molecular structures which do not cause unwanted immune stimulation suchas cytokine release and interferon response. The two new studies support the long-standing development approach of SilenceTherapeutics, which has focused its research on developing both a potentRNAi-mediating delivery system (AtuPLEX) and chemically-modified siRNA (AtuRNAi)molecules. Jeff Vick, CEO of Silence Therapeutics, said, "More than eight years ago,Silence Therapeutics recognized the need for, and pioneered the development of,a functional systemic RNAi delivery system that combines proprietary chemicalmodification and lipid technologies to achieve efficient intracellular uptakewithout triggering an immune system response. This approach has allowed us tosuccessfully demonstrate the inhibition of solid tumor growth and the spread ofmetastases. Silence continues to develop additional delivery technologies tobroaden the clinical applications of our promising new class of siRNAtherapeutics." Silence Therapeutics has previously reported in 2006, in two peer reviewedpublications in Gene Therapy3, 4, the functional in vivo delivery of differentAtuRNAi-lipoplexes (chemically modified siRNA molecules formulated in aproprietary lipid complex). In particular, Silence Therapeutics' AtuPLEXformulation was shown to both avoid immune responses (published datademonstrates lack of activation of interferon-alpha and IL-12) and induceRNAi-mediated gene silencing as demonstrated by the selective inhibition ofendogenous target-specific gene expression in vivo. Furthermore, independentpublications by Judge6 and Kim2 also demonstrate that the chemical modificationmodality utilized in AtuRNAi obviates an immune response. These Gene Therapy papers also show that the target-specific knockdown (genesilencing) resulted in the modulation of a specific biochemical signalingpathway containing the target, thus demonstrating the potential therapeuticbenefits in certain oncology indications. The multi-faceted approach that Silence Therapeutics has taken to realize theenormous potential of siRNA therapeutics was substantiated by Dr. Alan Sachs,Vice President for RNA Therapeutics at Merck Research Laboratories, a unit ofMerck, who was quoted in the New York Times,5 saying that "future versions ofRNA drugs could be encapsulated in fat globules and chemically modified. Thatwould help the drugs enter cells and keep them from setting off the immunesystem." Jeff Vick further commented, "That future is now. This is the exact approachpioneered by Silence Therapeutics. Our current pipeline is based on combiningour state-of-the-art AtuRNAi molecules and AtuPLEX drug delivery system. Wehave strong evidence that the siRNA therapeutics we are developing do entermammalian cells, are appropriately localized intracellularly, and do act byselectively silencing the specifically targeted gene. We believe by continuingto build on this unique expertise we will achieve our goal of becoming a globalleader in the RNAi space." Footnotes: Kleinman et. al., Nature1, "Sequence-and target-independent angiogenesissuppression by siRNA via TLR3 | doi:10.1038/nature06765; Received Publishedonline 26 March 2008." Kim et. al., Molecules and Cells2, Vol. 24, 247, 2007: "Immune Activation bysiRNA/Liposome Complexes in Mice Is Sequence-independent: Lack of a Role forToll-like Receptor 3 Signalling." Santel et. al., Gene Therapy3 2006 Sep;13(18):1360-70. "RNA interference in themouse vascular endothelium by systemic administration of siRNA-lipoplexes forcancer therapy." Santel et. al., Gene Therapy4 2006 Aug;13(16):1222-34. "A novel siRNA-lipoplextechnology for RNA interference in the mouse vascular endothelium." New York Times5, April 2, 2008. "Study is a Setback for Some RNA-Based Drugs." Adam D. Judge, Gurneet Bola, Amy C.H. Lee, Ian MacLachlan, Molecular Therapy6Vol. 13, No. 3, March 2006: "Design of Noninflammatory Synthetic siRNA MediatingPotent Gene Silencing in Vivo." - Ends - Enquiries: For further information, please contact the following: Silence Therapeutics plc European Contacts:+44(0)20 7307 1620 Citigate Dewe RogersonJeff Vick, Chief Executive Officer +44(0)20 7638 9571Melvyn Davies, Finance Director & Company Secretary David Dible Heather Keohane U.S. Contacts: LaVoie Group +1 - 978.745.4200 Bryan Murphy x 105 Tim Allison x 102 Notes to Editors: About Silence Therapeutics plc (www.silence-therapeutics.com) Silence Therapeutics plc (AIM:SLN) is a leading RNAi company. RNA interference(RNAi) can selectively 'silence' genes linked to the onset of disease. Silence Therapeutics has developed novel, proprietary short interfering RNA('siRNA') molecules, AtuRNAi, which provide a number of advantages overconventional siRNA molecules as they show increased stability against nucleasedegradation. In addition, the Company has developed a proprietary systemicdelivery system, AtuPLEX. This enables the delivery of siRNA molecules totargeted diseased tissues and cells, whilst increasing their bioavailability andintracellular uptake. In July 2007, Silence Therapeutics formed a research and developmentcollaboration with AstraZeneca to develop AtuRNAi against five specific targetsincluding those in respiratory indications. The Company's AtuRNAi technologyalso has been sublicensed to Pfizer through Quark's license to Pfizer of thecompound RTP-801i-14 for the treatment of Age-related Macular Degeneration (AMD)and a number of other indications. This compound entered the clinic in early2007. Silence Therapeutics also has licensed to Quark rights to the AtuRNAistructure for its proprietary compound AKIi-5. This compound is in a Phase Ihuman clinical study for treatment of acute kidney injury. In addition, SilenceTherapeutics expects to begin the clinical development of its own proprietaryAtuRNAi therapeutic molecules for systemic cancer indications in 2008. Silence Therapeutics is based in London, UK, and Berlin, Germany, and is listedon AIM. This information is provided by RNS The company news service from the London Stock Exchange