SLN.L Regulatory News (SLN)

30 July 2014

Silence Therapeutics plc

Licensee confirms favourable trial outcome

Silence Therapeutics plc, AIM: SLN ('Silence' or 'the Company'), a leader in the discovery, development and delivery of novel RNA interference (RNAi) therapeutics for the treatment of serious diseases, announces that licence holder Quark Pharmaceuticals, Inc. ('Quark') has confirmed favourable results in its Phase 2 trial for the use of QPI-1002 short interfering RNA (siRNA) for the prevention of delayed graft function (DGF) in kidney transplant patients (QRK.006B; ClinicalTrials.gov identifier: NCT00802347). The results were presented in an oral session on 28 July 2014 at the World Transplant Congress in San Francisco.

QPI-1002 is a systemically delivered siRNA-based inhibitor of the transient protein P53, a known contributor to kidney cell death and an underlying trigger of the injury that causes DGF. It is the first siRNA compound to be used systemically in human clinical trials. The siRNA modification used in this agent, known as AtuRNAi, was developed by Silence Therapeutics.

The Phase 2 trial was a randomised, placebo-controlled, multi-centre study, involving 331 dialysis-dependent patients in North America and Europe with chronic kidney disease who were undergoing deceased donor kidney transplantation. The primary objectives of the study were to assess the efficacy of QPI-1002 in the prevention of DGF and to further assess its safety and pharmacokinetics. The primary study endpoint was to achieve at least 30% relative risk reduction of DGF (defined as the need for dialysis within the first 7 days post-transplant, excluding dialysis in the first 24 hours due to hyperkalemia/hypervolemia) in QPI-1002-treated patients compared to placebo.

The overall QPI-1002 safety profile was consistent with the expected profile for transplant recipients, and similar in both treated and placebo groups. While the primary endpoint for the study was not met in the total study population (15.1% relative risk reduction of DGF), treatment with QPI-1002 was shown to result in a 30.5% relative reduction of DGF (p=0.111) in the largest patient subgroup prospectively defined in the study. These patients received Expanded Criteria Donor kidneys, entirely Cold Stored. There were a total of 177 patients in this stratum, accounting for 53% of the 332 randomised patients.

Additionally, among this prospectively defined subgroup of patients, QPI-1002 treatment significantly increased the dialysis free survival (time to first dialysis) in the first post-transplant month (Log rank p=0.04), reduced the mean duration of the first course of dialysis (13.4 vs 25.3 days); and reduced the number of dialysis sessions required in the first 30 days post-transplant (6.0 vs 11.2).

Quark is the exclusive worldwide licence holder for certain of Silence's IP used in QPI-1002 and first began its collaboration with Silence in April 2005. In August 2010, Quark entered into an agreement with Novartis International AG ('Novartis'), granting Novartis the exclusive worldwide licence option for the development and commercialisation QPI-1002. Silence is eligible to receive 15% of the proceeds of this option, should it be exercised.

Quark's announcement can be found here: http://news.morningstar.com/all/globe-news-wire/10091397/quark-pharmaceuticals-reports-favorable-results-from-phase-ii-clinical-trial-evaluating-investigational-sirna-qpi-1002.aspx

Ali Mortazavi, CEO of Silence Therapeutics said:

"This study has highlighted the safety and potency of our technology in humans. With more than 160 additional patients dosed with AtuRNAi, there is further valuable data to add to the safety record we already have. We have also seen some clinical activity and efficacy in this study, confirming the clinical utility of our technology.

"We are excited about the potential of AtuRNAi in this application and the progression of our IP toward commercial therapeutics."

Enquiries:

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

Silence Therapeutics is a leading RNAi (RNA interference) therapeutics platform technology company which has proprietary delivery systems. Combined, the RNAi and delivery platforms enable the development of multiple products to multiple drug targets allowing the development of novel therapeutics for diseases with high unmet medical need.

Listed on London's AIM since 2006, Silence is one of only a handful of listed companies globally with well-validated RNA delivery technology. It has a robust IP estate, with three Phase 2 trials already completed (pending results).

About Quark Pharmaceuticals, Inc.

Quark Pharmaceuticals, Inc., the world leader in novel therapeutic RNAi discovery and development, has the largest clinical-stage siRNA pipeline in the industry. The Company's fully integrated drug development platform spans therapeutic target identification to drug development. Quark's approach to delivery allows targeting of tissues and organs including the eye, kidney, ear, lung, skin, spinal cord and brain. Quark has three siRNA product candidates in clinical development in five different disease indications of which four are in Phase 2. Quark's Joint venture in China, Kunshan Ribo-Quark Pharmaceutical Inc, and its strategic partner in India, Biocon Limited, are part of Quark's worldwide clinical studies network.

Quark is headquartered in Fremont, California and operates research and development facilities in Boulder, Colorado and Ness-Ziona, Israel. For additional information visit www.quarkpharma.com

About Delayed Graft Function (DGF)

DGF is one of the most common complications during the immediate postoperative period in kidney transplantation, affecting 25-40% of deceased donor renal transplant recipients. DGF most often results from ischemia/reperfusion injury, when blood flow is re-established to the kidney following transplantation and initiates a chain of events that can lead to severe renal damage. DGF is associated with longer hospital stays and higher rates of graft rejection, which decreases transplanted kidney survival (graft survival). There is no currently marketed drug therapy for the prevention or treatment of DGF.