In 2004, Quark Pharmaceuticals and Silence entered a collaboration to discover AtuRNAi lead compounds against RTP801. In this program, Quark is contributing the disease-specific expertise, while Silence Therapeutics is contributing its siRNA know-how and intellectual property. In 2006, Pfizer in-licensed this compound (since renamed PF-4523655) for the treatment of age-related macular degeneration (AMD), diabetic retinopathy and other indications. As part of this collaboration, Silence may receive milestone payments of up to $95million plus royalties of which Silence has received $6million so far. PF-4523655 has completed two separate Phase II clinical trials for the treatment of diabetic macular Oedema (DME) and age-related macular degeneration (AMD).
In August 2010 Silence announced that its partner, Quark Pharmaceuticals has granted an option to Novartis to obtain an exclusive worldwide license to develop and commercialise QPI-1002, a p53 temporary inhibitor siRNA drug which incorporates Silence's AtuRNAi technology. Quark is currently conducting a Phase II clinical trial of QPI-1002 in the prophylaxis of delayed graft function in kidney transplant patients and has completed a Phase I trial in the prevention of acute kidney injury in patients undergoing cardiac surgery. Based on the announcement issued by Quark on 18 August 2010, and under the terms of Silence's agreement with Quark, Silence anticipates that its future milestone payments from this program could potentially exceed $82 million.
In 2007, Silence signed a multi-year, multi-target collaboration agreement with AstraZeneca. At the time, AstraZeneca paid an upfront of $15 million and agreed on milestone payments of up to $400 million plus royalties. The three-year collaboration is designed to discover and develop proprietary siRNA molecules against up to five specific targets provided by AstraZeneca. Silence and AstraZeneca will jointly collaborate in the early phase of identification and optimization of novel siRNA molecules. AstraZeneca retains responsibility for the clinical development and commercialization. The agreement is primarily in the respiratory field but includes an option to allow for targets that extend the collaboration into other disease areas of interest to AstraZeneca. In July 2010 the two companies agreed to an extension of this ongoing collaboration.
Delivery Collaboration Agreement Additionally, Silence and AstraZeneca entered into a second, separate small interfering RNA (siRNA) delivery collaboration in March 2008. Under this collaboration, the companies are leveraging a number of Silence's proprietary lipid delivery and targeting technologies to develop new and enhanced delivery approaches for RNA interference (RNAi) therapeutics. Under terms of the agreement, both companies retain the right to commercialize the novel delivery solutions that emerge from the collaboration. In April 2010, the two companies agreed to an extension for this ongoing collaboration.
In August 2009, Silence entered into a small interfering RNA (siRNA) delivery collaboration with Dainippon Sumitomo Pharma Co., Ltd. Under this collaboration, the companies are leveraging Silence’s proprietary siRNA molecules and multiple lipid delivery and targeting technologies to demonstrate functional delivery of RNA interference (RNAi) therapeutics to specific disease targets in the body. In March 2010, the two companies agreed to expand the collaboration to include additional disease targets selected by Dainippon Sumitomo. So far, Silence has received upfront payments of $2 million.
In September 2011 Silence and InteRNA Technologies B.V., a biopharmaceutical company developing pathway targeted microRNA-based therapeutics for cancer, entered into an agreement to develop novel microRNA therapeutics for the treatment of cancer. This will combine the delivery capabilities of Silence’s proprietary AtuPLEX delivery system with InteRNA's novel microRNAs. .
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In September 2011 Silence Therapeutics entered into an agreement with one of the world's leading global pharmaceutical companies to investigate the application of Silence's proprietary DACC delivery technology for intravenous delivery of short interfering RNA sequences to the pulmonary vascular endothelium. Under the terms of the agreement, Silence's partner will provide Silence with specific siRNAs, which Silence will formulate with its DACC delivery system. Silence and its partner will undertake in vitro and in vivo studies of the DACC formulated siRNAs developed under the agreement and select lead candidates for further evaluation.
In October 2011 Silence signed a delivery collaboration agreement with Mirna Therapeutics Inc., a biopharmaceutical company pioneering microRNA-based therapeutics for cancer, to assess the delivery capabilities of Silence's proprietary AtuPLEX™ and DBTC delivery systems for Mirna's novel microRNAs. Under the terms of the agreement, Mirna will provide Silence with specific miRNA sequences, which Silence will formulate with its AtuPLEX™ and DBTC delivery systems in order to develop multiple candidate drugs. Mirna will undertake in vitro and in vivo studies of the candidate drugs developed under the agreement and select lead candidates for further evaluation. Financial terms of the deal were not disclosed.
In January 2012 Silence signed an agreement with miRagen Therapeutics, Inc. , to assess the delivery potential of Silence's proprietary DBTC delivery system with miRagen's novel microRNA-based therapeutics. MiRagen is a pre-clinical stage biopharmaceutical company founded to develop innovative microRNA-based therapeutics for the treatment of cardiovascular and muscle disease. Under the terms of the agreement, miRagen will provide Silence with specific miRNA sequences, which Silence will formulate with its proprietary DBTC delivery system in order to develop multiple candidate drugs. MiRagen will undertake in vitro and in vivo studies of the candidate drugs developed under the agreement and select lead candidates for further evaluation.